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. 2021 Apr 9;10:280. [Version 1] doi: 10.12688/f1000research.52439.1

SARS-CoV-2 and the role of close contact in transmission: a systematic review

Igho J Onakpoya 1,a, Carl J Heneghan 1, Elizabeth A Spencer 1, Jon Brassey 2, Annette Plüddemann 1, David H Evans 3, John M Conly 4, Tom Jefferson 1
PMCID: PMC9636487  PMID: 36398277

Abstract

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. 

Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis.

Results: We included 181 studies: 171 primary studies and 10 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (31.6%) and acute care hospitals (15.2%). The overall reporting quality of the studies was low to moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) was 3.5-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if index cases had recurrent infection. Viral culture was performed in three studies of which two found viable virus; culture results were negative where index cases had recurrent infections. Ten studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 81-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection.

Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted via close contact settings. The risk of transmission is greater in household contacts. There was wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed to improve the quality reporting.

Keywords: Close contact, transmission, COVID-19, systematic review

Introduction

The SARS-CoV-2 (COVID-19) pandemic is a major public health concern. Based on WHO data, there have been over 120 million confirmed cases and over two and a half million deaths globally as of 20th March 2021 1 . Many national governments have implemented prevention and control measures and vaccines are now being approved and administered; the overall global spread of the virus now appears to be slowing. Current evidence from epidemiologic and virologic studies suggest SARS-CoV-2 is primarily transmitted via respiratory droplets and direct and indirect contact 2, 3 . However, controversy still exists about how the virus is transmitted and the relative frequency of the modes of transmission and if these modes may be altered in specific settings 4, 5 .

Although close contact is thought to be associated with transmission of SARS-CoV-2, there is uncertainty about the thresholds of proximity for “close contact” and the factors that may influence the transmission in a “close contact”. Furthermore, there is lack of clarity about how research should be conducted in the setting of transmission with close contact which may include transmission via any one of or the combination of respiratory droplets, direct contact, or indirect contact.

Several studies investigating the role of close contact in SARS-CoV-2 transmission have been published but the pathways and thresholds for transmission are not well established. The objective of this review was to identify, appraise and summarize the evidence from primary studies and systematic reviews investigating the role of close contact in the transmission of SARS-CoV-2. Terminology for this article can be found in Box 1.

Box 1. Terminology.

Close contact: Someone who was within 6 feet of an infected person for a cumulative total of 15 minutes or more over a 24-hour period starting from 2 days before illness onset (or, for asymptomatic patients, 2 days prior to test specimen collection) until the time the patient is isolated 1 ; The World Health Organization (WHO) additionally includes direct physical contact with a probable or confirmed case, direct care for a patient with probable or confirmed COVID-19 disease without using proper PPE, and other situations as indicated by local risk assessments.

Attack rate: The proportion of those who become ill after a specified exposure 2 .

Secondary attack rate: The probability that infection occurs among susceptible persons within a reasonable incubation period following known contact with an infectious person or an infectious source 3 .

Cycle threshold: The number of cycles required for the fluorescent signal to cross the threshold. Ct levels are inversely proportional to the amount of target nucleic acid in the sample 4 .

1 https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/operational-considerations-contact-tracing.html#:~:text=Close contact is defined by, time the patient is isolated

2 https://www.who.int/foodsafety/publications/foodborne_disease/Annex_7.pdf

3Halloran ME. Secondary Attack Rate. In: Peter A, Theodore C, editors. Encyclopedia of Biostatistics. New York: John Wiley & Sons Ltd; 2005

4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521909/

Methods

We are undertaking an open evidence review examining the factors and circumstances that impact on the transmission of SARS-CoV-2, based on our published protocol last updated on the 1 December 2020 (Version 3: 1 December 2020, Extended data: Appendix 1 6 ). This review aims to identify, appraise, and summarize the evidence (from peer-reviewed studies or studies awaiting peer review) examining the role of close contact in the transmission of SARS-CoV-2 and the factors that influence transmissibility. We are conducting an ongoing search in WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 for keywords and associated synonyms. For this review, we also conducted searches on PubMed. The searches for this update were conducted up to 20th December 2020 ( Extended data: Appendix 2 6 ). We did not impose any language restrictions.

We included studies of any design that investigated transmission associated with close contact but excluded predictive or modelling studies. We reviewed the results for relevance and for articles that appeared particularly relevant, we undertook forward citation matching to identify relevant results. We assessed the risk of bias of included primary studies using five domains from the QUADAS-2 criteria 7 ; we adapted this tool because the included studies were not primarily designed as diagnostic accuracy studies. We did not perform formal assessments of the quality of included systematic reviews but summarized their findings, including quality of their included studies as reported by the authors. We extracted the following information from included studies: study design characteristics including the definition used of “close contact”, population, main methods, and associated outcomes including the number of swab samples taken with frequency and timing of samples, and cycle thresholds and samples concentrations. We also extracted information on viral cultures including the methods used. One reviewer (IJO) assessed the risk of bias from primary studies, and these were independently verified by a second reviewer (EAS). One reviewer (IJO) extracted data from the included primary studies, and these were independently checked by a second reviewer (CJH). One reviewer (CJH) extracted data from the included systematic reviews, and these were independently checked by a second reviewer (IJO). Disagreements in the data extraction or bias assessments were resolved by consensus. We presented the results in tabular format, and bar charts used to present the frequency of positive tests. We reported results of specific subgroups of studies where relevant. Because of substantial heterogeneity across the included studies, we considered meta-analyses inappropriate.

Results

We identified 1202 non-duplicate citations of which 229 were considered eligible ( Figure 1). We excluded 48 full-text studies for various reasons (see Extended data: Appendix 3 6 for the list of excluded studies and reasons for exclusion). Finally, we included 181 studies: 171 primary studies and 10 systematic reviews (see Extended data: Appendix 4 for references to included studies). The main characteristics of the included primary studies and systematic reviews are shown in Table 1 and Table 2, respectively.

Figure 1. Flow diagram showing the process for inclusion of studies assessing close contact transmission in SARS-CoV-2.

Figure 1.

Table 1. Close contact study characteristics.

Study ID Country Study Design/Setting Type of
transmission
Population/environment Test method Timing of sample collection Viral
culture
Cycle threshold Other information
Abdulrahman 2020 Bahrain Observational comparative
Country-wide 09/2020
Community Before and after study of subjects
attending 2 religious events
PCR Not reported No >40 was considered
negative
A 10-day period before the event was compared to a 10-day
period beginning 10 days after the event.
All symptomatic individuals and close contacts to a confirmed
case were tested.
Positive and negative controls were included for quality
control purposes.
Adamik 2020 Poland Observational Home Household 9756 index cases; 3553 secondary cases Not reported Not reported No No Only cases for which clear epidemiological links were
registered as household transmission together with their
source cases were included. Cases in social care units and
households of minimum 15 inhabitants were removed from
the analysis, as an initial analysis revealed that those were
not representative for the overall population, due to over-
represented comorbidities and severe cases.
Agergaard 2020 Denmark Home quarantine with 1
asymptomatic index case
11/03/2020 to 01/04/2020
Household Family cluster of 5: Index case arranged
a self-imposed 2-week home quarantine
along with family of four
PCR
Serology
Not reported for PCR No Not specified for PCR Index case recently returned from skiing trip in Austria
iFlash SARS-CoV-2 N/S IgM/IgG cut-off: ≥12 AU/ml = positive.
DiaSorin SARS-CoV-2 S1/S2 IgG cut-off: ≥15 AU/ml = positive
Angulo-Bazán 2020 Peru Observational retrospective
Household 23/04/2020 to
02/05/2020
Household 52 households in Metropolitan Lima with
only one member with COVID-19
Contacts cohabited in same home with
index case
RT-PCR (index)
Serology
Not reported No Not specified Evaluation was conducted 13.6 ± 3.7 days after the diagnostic
test
Armann 2020 Germany Observational - cross-sectional
Schools, homes May to October
2020
Local
Household
1538 students and 507 teachers were
initially enrolled, and 1334 students and
445 teachers completed both study visits.
Serology Week 0 and Week 16 No N/A an index (S/C) of < 1.4 was considered negative whereas
one >/= 1.4 was considered positive) and an ELISA detecting
IgG against the S1 domain of the SARS-CoV-2 spike protein
(Euroimmun® Anti-SARS CoV-2 ELISA) (a ratio < 0.8 was
considered negative, 0.8–1.1 equivocal, > 1.1 positive)
Arnedo-Pena 2020 Spain Retrospective cohort Homes
February-May 2020
Household 347 index cases: 745 household contacts RT-PCR Not reported No Not specified COVID-19 cases of community outbreaks and from institutions
as nursing homes were excluded.
Secondary attack rate was defined as the proportion of
secondary cases from the total of contacts that live in the
household of index case.
Baker 2020 USA Observational
Acute-care hospital
Nosocomial 44 HCWs who provided care for a
hospitalized patient with COVID-19 without
PPE due to delayed diagnosis of COVID-19
RT-PCR Not reported No Not specified Contact and droplet precautions (including eye protection)
were instituted
Baettig 2020 Switzerland Retrospective case series
Military canton
March 2020
Local 1 index case; 55 contacts RT-PCR Serology PCR: Within 24 hrs of index case
for symptomatic subjects
Serology: 14 days post-exposure
No Not reported Positive cases were defined with two positive PCR testing for
SARS-CoV-2 from nasopharyngeal swabs.
Bao 2020 China Observational Entertainment
venue January and February
2020
Community Potentially exposed workers, customers
and their family members potentially
exposed to COVID‐19 subject at a
swimming pool
RT-PCR Not reported No Not specified Men and women exhibited different usage behaviour in that
male bathers occupied the entire area, but mainly stayed
at the lounge hall, while female bathers always went home
after a bath. The temperature and humidity were significantly
higher than what they would have been in an open
air‐conditioning environment.
Basso 2020 Norway Observational study
Hospital
Nosocomial Quarantined HCWs exposed to COVID-19
patient
PCR
Serology
Approximately 2 weeks after viral
exposure; 3 weeks for serology
No N/A
S/CO ratio ≥1 is
positive for antibody
The HCWs were quarantined for 2 weeks due to participation
in aerosol-generating procedures (AGPs) with insufficient
personal protective equipment (PPE), or close contact viral
exposure (defined as ≤2 m for ≥15 min).
Bays 2020 USA Observational study
Community hospital and
university medical centre
February and March, 2020
Nosocomial Two index patients and 421 exposed HCWs RT-PCR Not reported No Not specified Exposed staff were identified by analyzing the EMR and
conducting active case finding in combination with structured
interviews. They wore neither surgical masks nor eye
protection, and were risk stratified based on examination
of the medical record and subsequent phone interviews as
follows: high risk: nose or mouth exposed during intubation
or bronchoscopy; moderate: nose or mouth exposed and for
over 2 minutes; and low: nose or mouth exposed under 2
minutes. Ct was 25 for 1 index case - day 15
Bi 2020 China Retrospective cohort
Home or quarantine facility
January-February 2020
Local
Household
Community
391 SARS-CoV-2 cases and 1286 close
contacts
RT-PCR RT-PCR No Not reporred Close contacts were identified through contact tracing of
a confirmed case and were defined as those who lived in
the same apartment, shared a meal, travelled, or socially
interacted with an index case 2 days before symptom onset.
Casual contacts (eg, other clinic patients) and some close
contacts (eg, nurses) who wore a mask during exposure were
not included in this group.
Blaisdell 2020 USA Observational study
4 overnight camps
June–August 2020
Community Multilayered prevention and mitigation
strategy
642 children and 380 staff members, aged
7–70 years
RT-PCR 4.1 to 9.1 days after camp arrival No Not specified Hygiene measures: Precamp quarantine, pre- and postarrival
testing and symptom screening, cohorting, and physical
distancing between cohorts. In addition, camps required use
of face coverings, enhanced hygiene measures, enhanced
cleaning and disinfecting, maximal outdoor programming, and
early and rapid identification of infection and isolation.
Böhmer 2020 Germany Observational
Workplace, home
January-February 2020
Local
Household
1 index case; 241 contacts RT-PCR WGS 3–5 days post-exposure No Not reported
Boscolo-Rizzo 2020 Italy Cross-sectional
Homes
March to April 2020
Household 179 primary cases; 296 household contacts RT-PCR Unclear No Not reported
Brown 2020 USA Survey - cross-sectional
Classroom
February to March, 2020
Local Students exposed to an index case
(teacher)
Serology 2 weeks post-exposre to index
case
No Reciprocal titers of
>400 considered
positive
Reciprocal titers
of >100 but
<400 considered
indeterminate
Burke 2020 USA Observational prospective
Homes
February to March 2020
Household 10 primary cases; 445 close contacts Not reported Within 2 weeks of exposure to
infected case
No Not reported 19 (4%) of the 445 contacts were members of a patient’s
household, and five of these 19 contacts continued to have
household exposure to the patient with confirmed COVID-
19 during the patient’s isolation period; 104 (23%) were
community members who spent at least 10 minutes within
6 feet of a patient with confirmed disease; 100 (22%) were
community members who were exposed** to a patient in a
health care setting; and 222 (50%) were health care personnel
Canova 2020 Switzerland Observational case series
Primary care setting
Nosocomial 1 index case; 21 HCWs who interacted with
index case without PPE
RT-PCR 7 days after the initial exposure No Not reporred
Cariani 2020 Italy Retrospective
Hospital
March to April 2020
Nosocomial HCWs in close contact with SARS-CoV-2-
positive cases (patients, co-workers, or
relatives), or with symptoms of RTI
RT-PCR Not reported No <40 considered
positive
Charlotte 2020 France Retrospective
Indoor choir rehearsal
March 2020
Community Nonventilated room; sitting less close to
one another than usual, but at a distance
of <1.82m
RT-PCR Not reported No Not reported
Chaw 2020 Brunei Observational
Various
March 2020
Local
Community
Primary cases: Presumably infected at
religious event in Malaysia
Secondary cases: Epidemiologic link to a
primary case
RT-PCR Not reported No Not reported Household, workplace, social, and a local religious gathering.
Initial cluster of SARS-CoV-2 cases arose from 19 persons
who had attended the Tablighi Jama’at gathering in Malaysia,
resulting in 52 locally transmitted cases.
Chen 2020 China Aircraft
24 January 2020
Aircraft Close contact to 2 passengers presenting
with a fever and URTI symptoms
RT-PCR Not reported No Not reported The aircraft was equipped with air handling systems.
Chen 2020a China Retrospective observational
Home or workplace
January-March 2020
Local
Household
69 recurrent-positive patients; 209 close
contacts
RT-PCR Every 3 days No Not specified
Chen 2020b China Prospective cohort
Hospital
January-February 2020
Nosocomial 5 index patients; 105 HCWs RT-PCR
Serology
From 14 days post-exposure: 1st
& 14th day of quarantine
No <40 considered
positive
Chen 2020c China Observational
Various
January to March 2020
Local
Household
Community
Nosocomial
157 locally reported confirmed cases,
30 asymptomatic infections; 2147 close
contacts
Not reported Unclear No Not reported Family members, relatives, friends/pilgrims, colleagues/
classmates, medical staff, and general personnel judged by
the investigator.
Cheng 2020 Taiwan Observational
Homes, hospital
January to March 2020
Household
Nosocomial
100 confirmed cases of confirmed; 2761
close contacts
RT-PCR Unclear No Not reported
Chu 2020 USA Observational
Various
January 2020
Community Close contacts for an early confirmed case
of COVID-19
RT-PCR
Serology
Unclear No Antibody titers
>400 considered
seropositive.
Office, Community, Urgent care clinic identified via contact
tracing
Chu 2020a USA Retrospective cohort study
Household
Household Household contacts of primary cases
defined as children and adolescents with
lab-confirmed COVID-19 (n=224)
Not reported Not reported No Not reported Did not distinguish between confirmed and probable cases
among household contacts. A “primary case” is camp attendee
with the earliest onset date in the household and a “secondary
case” as a household contact with confirmed or probable
COVID-19.
Contejean 2020 France Observational Comparative
Tertiary-care university hospital
Feb-Mar 2020
Nosocomial HCW exposed to COVID-19 patients RT-PCR Not reported No Not reported:
result was +ve if
3/5 of gene targets
amplified
Hygiene measures: All employees were encouraged to wear
a face mask as often as possible in hospital (particularly in
the presence of other persons), to wash/disinfect their hands
regularly (and after every contact with other persons), to stay
at least 2 meters away from others, to cover their mouth
and nose with a tissue or sleeve when coughing or sneezing,
to put used tissues in the bin immediately and wash hands
afterwards, to avoid touching eyes, mouth. Educational
messages were released on the internal website and on
posters placed in all hospital premises.
COVID-19 National Emergency Response Center 2020 S. Korea Observational
Various
January to March 2020
Local
Household
Nosocomial
30 cases; 2,370 contacts RT-PCR Not reported No Not reported Homes, work, hospitals
Danis 2020 France Observational case series
Chalet, school
January to February 2020
Local
Household
I adult case with 15 contacts in chalet; 1
paediatric case with 172 school contacts
RT-PCR Within 5 days of diagnosis of
cases
No Not reported The index case stayed 4 days in the chalet with 10 English
tourists and a family of 5 French residents. One pediatric
case, with picornavirus and influenza A coinfection, visited 3
different schools while symptomatic.
Dattner 2020 Israel Observational
Home
March to June 2020
Household 637 households, average household size of
5.3
RT-PCR
Serology
Serology: 4 weeks post PCR
testing
No Not reported
de Brito 2020 Brazil Observational descriptive
Household
April-May 2020
Household Socially distanced household contacts of
index case
RT-PCR
Serology
Serology: 4 weeks post-exposure
PCR unclear
No Not reported Index case: First member of the cluster who had symptoms
and who had a known risk of exposure outside the household
during the family's stay in the same condominium; secondary
case: Contacts with the index case. Asymptomatic patients:
Those who had household contact and positive serology but
no symptoms. Probable cases corresponded to confirmed
case contacts who developed symptoms compatible with
COVID despite negative serology and/or negative RT-PCR
results.
Deng 2020 China Observational
Home
January to February 2020
Household 27 cases; 347 close contacts Not reported Not reported No Not reported
Desmet 2020 Belgium Observational - cross-sectional
School November 2019 to
March 2020
Local 84 aged between 6 and 30 months
attending daycare
RT-PCR First weeks of the epidemic in
Belgium
No Not reported
Dimcheff 2020 USA Survey: cross-sectional
Tertiary-care referral facility
June 8 to July 8, 2020
Community
Nosocomial
Household
HCW exposed to COVID-19 patients either
in or outside hospital
Serology 8 weeks post-exposure No Not reported Hygiene measures: Daily COVID-19 symptom screening
upon building entry, exclusion of visitors from the facility, and
institution of telework in remote offices or at home, isolation
of confirmed COVID-19 patients, conversion of COVID-19
wards to negative pressure environments, use of PAPRs) or
N95 respirators along with PPE by staff.
Dong 2020 China Observational
Homes
Household 135 cases; 259 close contacts Not reported Not reported No Not reported
Doung-ngern 2020 Thailand Retrospective case-control
Various
March to April 2020
Local 3 large clusters in nightclubs, boxing
stadiums, and a state enterprise office
RT-PCR Not reported No Not reported Hygiene measures: Consistent wearing of masks,
handwashing, and social distancing in public.
Draper 2020 Australia Observational Various
March to April 2020
Local
Household
Nosocomial
28 cases; 445 close contacts RT-PCR Within 2 weeks of exposure to
infected case
No Not reported Cruise ship, homes, aircraft, hospital
Dub 2020 Finland Retrospective cohort (2)
School and Household
Local
Household
School and household contacts of 2 index
cases who contracted COVID-19 at school
RT-PCR
Serology
Serology: >4 weeks post-exposure No MNT titre of ≥ 6
considered positive
FMIA titre 3·4 U/ml
considered positive
Expert Taskforce 2020 Japan Observational prospective
Cruise ship
February 2020
Local 3,711 persons in cruise ship RT-PCR Not reported No Not reported Passengers were allowed a 60-minute period on an exterior
deck each day, during which they were instructed to wear
masks, refrain from touching anything, and maintain a 1-meter
distance from others. Monitors observed these periods. After
each group came a 30-minute period in which the areas were
disinfected. Room cleaning was suspended. Food and clean
linens were delivered to cabin doors by crew, and dirty dishes
and linens were picked up at cabin doors by crew.
Only symptomatic close contacts were tested initially.
Fateh-Moghadam 2020 Italy Observational Various
March to April 2020
Community 2,812 cases; 6,690 community contacts Not reported Not reported No Not reported Institutional settings including nursing homes, hospitals, day
and residential centers for the disabled and similar structures,
and convents
Firestone 2020 USA Observational retrospective
Motorcycle rally
August-September 2020
Local 51 primary event-associated cases, and 35
secondary or tertiary cases
RT-PCR
WGS
Phylogenetic analysis
Unclear No Not reported Secondary cases: Laboratory-confirmed infections in persons
who did not attend the rally but who received SARS-CoV-
2–positive test results after having contact with a person who
had a primary case during their infectious period. Tertiary
cases were laboratory-confirmed cases in persons who had contact with a person who had
a secondary case during their
infectious period.
SARS-CoV-2 RNA-positive clinical specimens were obtained
from clinical laboratories, and
Fontanet 2020 France Retrospective cohort study
School
March to April 2020
Local 661 participants: pupils, their parents
and siblings, as well as teachers and non-
teaching staff of a high-school
Serology 10 weeks No N/A
Fontanet 2020a France Retrospective cohort study
Schools
April 2020
Local 510 participants: pupils, their parents
and siblings, as well as teachers and non-
teaching staff of a high-school
Serology 10 weeks No N/A 6 primary schools
Gan 2020 China Observational retrospective
survey
Various
January-February 2020
Local
Household
Community
1 052 cases in 366 epidemic clusters Not reported Not reported No Not reported Family living together, gathering dinner, collective work, ride-
thy-car, other aggregation exposure,
Ghinai 2020 USA Observational
2 Social gatherings
January-March 2020
Community 16 cases (7 confirmed and 9 probable) (1
index case)
RT-PCR Not reported No Not reported A birthday party, funeral, and church attendance.
Gong 2020 China Observational
Various
January-February 2020
Household
Community
3 clusters: 5 index cases; 9 close contacts RT-PCR Not reported No Not reported Travelling and dining, or were living together
Gong 2020 China Observational
Karaoke room
January 2020
Local 14 people exposed to 2 index cases in a karaoke room RT-PCR
Serology
PCR: Within 72 hrs post-exposure
Serology: 6 weeks post-exposure
No Not reported
Hamner 2020 USA Observational
Choir practice
March 2020
Local 1 index case; 60 close contacts RT-PCR Within 2 weeks of index case No Not reported
Han 2020 S. Korea Observational
Spa facility
Mar-April 2020
Community Contacts for 10 index cases from Spa
facility
RT-PCR Not reported No Not reported
Heavey 2020 Ireland Observational
School
March 2020
Local 6 index cases; 1155 contacts Not reported Not reported No No Three paediatric cases and three adult cases of COVID-19 with
a history of school attendance were identified. Exposed at
school in the classroom, during sports lessons,
music lessons and during choir practice for a religious ceremony, which
involved a number of schools mixing in a church environment.
Helsingen 2020 Norway RCT
Training facilities
May-June 2020
Local Members of the participating training
facilities age 18 years or older who were
not at increased risk for severe Covid-19
RT-PCR
Serology
Serology: 4 weeks after start
of study
No Not reported Hygiene measures: Avoidance of body contact; 1 metre
distance between individuals at all times; 2 metre distance for
high intensity activities; provision of disinfectants at all work
stations; cleaning requirements of all equipment after use by
participant; regular cleaning of facilities and access control
by facility employees to ensure distance measures and avoid
overcrowding. Changing rooms were open, but showers and
saunas remained closed.
All participants were mailed a home-test kit including two
swabs and a tube with virus transport medium for SARS-CoV-2
RNA
Hendrix 2020 USA Observational
Hair salon
May 2020
Local Contacts for 2 stylists who tested positive
for COVID-19
PCR Not reported No Not reported Hygiene measures: During all interactions with clients at
salon A, stylist A wore a double-layered cotton face covering,
and stylist B wore a double-layered cotton face covering or a
surgical mask.
Hirschman 2020 USA Observational study
Home and social gatherings
June 2020
Household
Community
2 index cases; 58 primary and secondary
contacts
RT-PCR Unclear No Not reported
Hobbs 2020 USA Case-control study
University Medical Centre
September-November 2020
Local
Household
Community
397 children and adolescents: Cases 154;
controls 243
RT-PCR Not reported No Not reported
Hoehl 2020 Germany Observational
Daycare Centre
12 weeks (June-Sept 2020)
Local
Community
Attendees and staff from 50 daycare
centres
RT-PCR Not reported No Not reported Hygiene measures: Barring children and staff with symptoms
of COVID-19, other than runny nose, from entering the
facilities, as well as denying access to individuals with known
exposure to SARS-CoV-2. Access to the facilities was also
denied to children if a household member was symptomatic,
or was in quarantine due to contact with SARS-CoV-2. Wearing
of masks was not mandatory for children or nor staff. The
access of caregivers to the facilities was limited.
Hong 2020 China Observational prospective
Home
January-April 2020
Household 9 patients with recurrent infection; 13
close contacts
RT-PCR
Serology
NGS
After re-admission of index
patients.
No Not reported
Hu 2020 China Observational retrospective
Various
January to April 2020
Household
Community
1178 cases; 15,648 contacts Not reported Not reported No Not reported Homes, social events, travel, other settings
Hua 2020 China Observational retrospective
Home
January to April 2020
Household Children and adult contacts from the 314
families
RT-PCR Not reported No Not reported
Huang 2020 China Prospective contact-tracing study
Restaurant, home
January 2020
Household
Community
1 indes case; 22 close contacts RT-PCR Within 3 days of index cases No Not reported Close contacts quarantined at home or hospital
Huang 2020a Taiwan Retrospective case series
Various
January-April 2020
Local
Household
Community
Nosocomial
15 primary cases: 3795 close contacts RT-PCR Not reported No Not reported Aircraft, home, classroom, workplace, hospital
Islam 2020 Bangladesh Observational
Various
March to June 2020
Local
Household
Community
Nosocomial
181 cases; 391 close contacts Not reported Not reported No Not reported Household, health care facility, funeral ceremony, public
transportation, family members, and others
Jia 2020 China Observational
Home
January to February 2020
Household 11 clusters (n=583) RT-PCR Not reported No <37 considered
positive
A close contact was defined as a person who did not take
effective protection against a suspected or confirmed case 2
d before the onset of symptoms or an asymptomatic infected
person 2 d before sampling.
Ct-value of 40 or more was defined as negative.
Jiang 2020 China Observational
Home
January to February 2020
Household
Community
8 index cases, 300 contacts rRT-PCR
WGS
Phylogenetic
analysis
Every 24 hours for 2 weeks No <37 considered
positive
Ct value ≥40 was considered negative. The maximum
likelihood phylogenetic tree of the complete genomes was
conducted by using RAxML software with 1000 bootstrap
replicates, employing the general time-reversible nucleotide
substitution mode
Jing 2020 China Retrospective cohort study
Homes
January-February 2020
Household 195 unrelated close contact groups (215
primary cases, 134 secondary or tertiary
cases, and 1964 uninfected close contacts)
RT-PCR Days 1 and 14 of quarantine No Not reported
Jing 2020a China Observational study
Homes, public places
February 2020
Household
Community
68 clusters involving 217 cases RT-PCR Not reported No Not reported
Jones 2020 UK
France
Observational
Super League Rugby
August to October 2020
Local 136: 8 index cases: 28 identified close
contacts and 100 other players
RT-PCR Within 14 days of match day No Not specified: Ct for index cases 17.8 to 27 Close contacts were defined by analysis of video footage
for player interactions and microtechnology (GPS) data for
proximity analysis. All participants were within a ≤7-day RT-PCR
screening cycle
Kang 2020 S. Korea Observational
Night clubs
April-May 2020
Local 96 primary cases and 150 secondary cases;
5,517 visitors
Not reported Not reported No Not reported
Kant 2020 India Retrospective (contact tracing)
Regional Medical Research
Centre
May 2020
Local
Community
Nosocomial
1 index case diagnosed post-mortem;
number of exposures unclear
RT-PCR Unclear No Not reported Contacts traced: People from the market where the index case
had his shop, his treating physicians, people who attended his
funeral, family members and friends
Kawasuji 2020 Japan Case-control study
University Hospital
April-May 2020
Nosocomial 28 index cases: 105 close contacts RT-PCR Unclear No Not reported Index patients and those with secondary transmission were
estimated based on serial intervals in the family clusters.
Khanh 2020 Vietnam Retrospective
Aircraft
March 2020
Community 1 index case: 217 close contacts PCR 4 days after positive test result of
index case
No Not reported Successfully traced passengers and crew members were
interviewed by use of a standard questionnaire, tested for
SARS-CoV-2
Kim 2020 S. Korea Retrospective observational
Home setting
January-April 2020
Household 107 paediatric index cases: 248 household
members of which 207 were exposed
RT-PCR Within 2 days of COVID-19
diagnosis of the index case
No Ct value of ≤35 is
positive and >40 is
negative
Guardian wore a KF94 (N95 equivalent) mask, gloves, full body
suit (or waterproof long-sleeve gowns) and goggles.
Kim 2020a S. Korea Case series
Various
January-February 2020
Household
Community
1 index case; 4 close contacts RT-PCR 4 days post-exposure No N/A 2 household contacts, 1 church contact, 1 restaurant
Kim 2020b S. Korea Retrospective observational
University hospital
February 2020
Nosocomial 4 confirmed cases: 290 contacts RT-PCR Within 8 days of index case
diagnosis
No Ct <35 was considered positive Medical staff in the triage room used level-D PPE and everyone
in the hospital was encouraged to wear masks and follow
hand hygiene practices. Contact with confirmed COVID-19
cases was frequent among inpatients and medical support
personnel.
Kumar 2020 India Observational
Community
March-May 2020
Community 144 source cases: RT-PCR Unclear No Not reported Persons with symptoms of ILI and SARI as well as known high-
risk contacts of a confirmed COVID-19 patient were included.
Kuwelker 2020 Norway Prospective case-ascertained
study
Homes
Feb-April 2020
Household 112 index cases; 179 household members Serology 6–8 weeks after symptom onset
in the index case.
No N/A Single-person households were excluded from the analysis.
Serum samples from index cases and household members
were collected 6–8 weeks after symptom onset in the index
case.
Kwok 2020 Hong Kong Retrospective observational
Quarantine or isolation
February 2020
Local
Household
53 cases; 206 close contacts Not reported Not reported No Not reported A secondary case referred to the first generation of infection
induced by an index case following contact with this case
Ladhani 2020 UK Prospective
Care homes
April 2020
Nosocomial 6 London care homes reporting a
suspected outbreak (2 or more cases); 254
staff members
RT-PCR Not reported No Not reported 254 of 474 (54%) staff members provided a nasal self-swab; 12
were symptomatic at the time of swabbing
Ladhani 2020a UK Prospective
Care homes
April 2020
Nosocomial 6 London care homes reporting a
suspected outbreak (2 or more cases); 254
staff members; 264 residents
RT-PCR Not reported Yes Unclear: Ct values <35 were cultured 254 of 474 (54%) staff members provided a nasal self-swab; 12
were symptomatic at the time of swabbing
Laws 2020 USA Prospective cohort
Home setting
March-May 2020
Household 1 pediatric index case: 188
household contacts
RT-PCR Study enrollment (day 0); study
close-out (day 14)
No Not reported Index case: household member with earliest symptom onset
(and positive SARS-CoV-2 RT-PCR test result).
Community prevalence in the 2 metropolitan areas was low
during this time, and both were under stay-at-home orders.
All enrolled index case patients and household contacts
were followed prospectively for 14 days. Five households
were selected for intensive swabbing requiring collection of
respiratory specimens from all household members during
four interim visits regardless of symptom presence.
Laxminarayan 2020 India Observational
Various
April to August 2020
Local
Household
Community
3,084,885 known exposed contacts Not reported Not reported No Not reported Individual-level epidemiological data on cases and contacts,
as well as laboratory test results, were available from 575,071
tested contacts of 84,965 confirmed cases.
Lee 2020 S. Korea Observational
Hospital
February-June 2020
Household 12 paediatric cases; 12 guardians as close
contact. All guardians used PPE
Not reported Not reported No Not reported
Lee 2020a S. Korea Observational
Homes
February to March 2020
Household 23 close contacts PCR Unclear No Not reported
Lewis 2020 USA Observational
Homes
March to April 2020
Household 58 households (Utah, n = 34; Wisconsin
n = 24), 58 primary patients and 188
household contacts
RT-PCR
Serology
Not reported No Not reported
Li 2020 China Observational
Home setting
Feb 2020
Household Family cluster of 1 index case: 5 household
contacts
RT-PCR One day after index case tested
positive
No Not reported Unknown when index case started shedding virus
Li 2020a China Observational case series
Home, hospital
January-February 2020
Household
Nosocomial
2-family cluster of 1 index case: 7 close
contacts
Not reported Not reported No Not reported
Li 2020b China Retrospective observational
Home
January-February 2020
Household 3-family cluster of 3 index cases: 14 close
contacts
RT-PCR Every 2–3 days until hospital
discharge.
No <38 considered
positive
Li 2020c China Retrospective observational
Home
January-March 2020
Household 30 cases from 35 cluster-onset families
(COFs) and 41 cases from 16 solitary-onset
families (SOFs)
Not reported Not reported No Not reported
Li 2020d China Observational
Household
February to March 2020
Household 105 index patients; 392 household
contacts
RT-PCR Within 2 weeks of exposure to
infected case
No Not reported
Liu 2020 China Retrospective observational
Home setting
Feb 2020
Household Family cluster of 1 index case: 7 household
contacts
RT-PCR Immediately after index case
tested positive
No If both the
nCovORF1ab and
nCoV-NP showed
positive results,
COVID-19 infection
was considered
Unclear whether the index case was actually first case
Liu 2020a China Retrospective case series
Hospital
January 2020
Nosocomial 30 HCWs with direct contact with patients RT-PCR Not reported No <40 considered
positive
30 cases have a history of direct contact with patients with
neo-coronary pneumonia (within 1 m), 1 to 28 contacts, an
average of 12 (7,16) contact times, contact time of 0.5 to 3.5 h,
the average cumulative contact time of 2 (1.5, 2.7)h.
Liu 2020b China Retrospective cohort study
Various
January-March 2020
Household
Community
Nosocomial
1158 index cases: 11,580 contacts RT-PCR Every several days No Not reported Homes, social venues, various types of transportations
Liu 2020c China Prospective observational Unclear 147 asymptomatic carriers: 1150 close
contacts
RT-PCR Not reported No Not reported RT-PCR for asymptomatic carriers - testing method not
described for close contacts
López 2020 USA Retrospective contact tracing
School setting
April-July 2020
Local
Household
12 index pediatric cases: 101 facility
contacts; 184 overall contacts
RT-PCR Not reported No Not reported Index case: first confirmed case identified in a person at the
child care facility
Primary case: Earliest confirmed case linked to the outbreak.
Overall attack rates include facility-associated cases, nonfacility
contact cases iand all facility staff members and attendees and
nonfacility contacts
Lopez Bernal 2020 UK Observational
Homes
January to March 2020
Household
Community
233 households with two or more people;
472 contacts.
PCR Unclear No Not reported Healthcare workers, returning travellers and airplane
exposures were excluded.
Lucey 2020 Ireland Observational
Hospital
March-May 2020
Nosocomial 5 HCWs in cluster 1; 2 HCWs in cluster 3;
HCW in cluster 2 not specified; 52 patients
infected with SARS-CoV-2;
RT-PCR
WGS
Phylogenetic
analysis
Not reported No Not reported SARS-CoV-2 RNA was extracted from nasopharyngeal swabs
obtained from COVID-19 cases and their corresponding HCWs
were sequenced to completion.
HA COVID-19 was classified into two groups according to the
length of admission: >7 days and >14 days.
The majority of patients required assistance with mobility
(65%) and selfcare (77%)
Luo 2020 China Observational retrospective
Public transport
January 2020
Community 1 index case; 243 close contacts RT-PCR Within 2 weeks of exposure to
index case
No Not reported The tour coach was with 49 seats was fully occupied with all
windows closed and the ventilation system on during the
2.5-hour trip.
Luo 2020a China Prospective cohort study
Various
January to March 2020
Household
Community
Nosocomial
391 index cases; 3410 close contacts RT-PCR
Serology
Every 24 hours. No Not reported Homes, public transport; healthcare settings, entertainment
venues, workplace, multiple settings
Lyngse 2020 Denmark Retrospective
Homes
February to July 2020
Household 990 primary cases; 2226 household
contacts
Not reported Within 14 days of exposure to
primary case
No Not reported Secondary cases: those who had a positive test within 14
days of the primary case being tested positive. 3 phases of
epidemic examined.
Assumed that the secondary household members were
infected by the household primary case, although some of
these secondary cases could represent co-primary cases. A
longer cutoff time period could result in misclassification of
cases among household members with somewhere else being
the source of secondary infections.
Ma 2020 China Observational
Medical isolation
Unclear 1665 close contacts RT-PCR Not reported No Not reported
Macartney 2020 Australia Prospective cohort study
Educational settings
April to May 2020
Local 27 primary cases; 633 contacts RT-PCR, serology, or both PCR: 5–10 days after last case
contact if not previously collected
Serology: day 21 following last
case contact.
No Not reported Index case: The first identified laboratory-confirmed case
who attended the facility while infectious. A school or ECEC
setting primary case was defined as the initial infectious case
or cases in that setting, and might or might not have been
the index case.
Primary case: Initial infectious case or cases in that setting,
and might or might not have been the index case
Secondary case: Close contact with SARS-CoV-2 infection
(detected through nucleic acid testing or serological testing,
or both), which was considered likely to have occurred via
transmission in that educational setting.
Malheiro 2020 Portugal Retrospective cohort study
Homes
March to April 2020
Household Intervention group (n=98), Control (n=453) Not reported Not reported No Not reported The intervention group comprised all COVID-19 confirmed
cases that were either identified as close contacts of an
index caseor returned from affected areas and placed under
mandatory quarantine, with daily follow-up until laboratory
confirmation of SARS-CoV-2 infection. The control group
included all COVID-19 confirmed cases that were not subject
to contact tracing nor to quarantine measures preceding the
diagnosis.
Maltezou 2020 Greece Retrospective observational
Home setting
February to June 2020
Household 203 SARS-CoV-2-infected children; number
of index cases and close contacts unclear
RT-PCR Not reported No Ct >38 considered
negative
A family cluster was defined as the detection of at least 2
cases of SARS-CoV-2 infection within a family. First case was
defined as the first COVID-19 case in a family. High, moderate,
or low viral load (Ct <25, 25–30 or >30, respectively)
Maltezou 2020a Greece Retrospective observational
Home setting
February to May 2020
Household 23 family clusters of COVID-19; 109
household members
RT-PCR Not reported No <25, 25–30 or >30 A family cluster was defined as the detection of at least 2
cases of SARS-CoV-2 infection within a family. Index case was
defined as the first laboratory-diagnosed case in the family.
Mao 2020 China Cross-sectional study
Home, family gatherings
January-March 2020
Household
Local
67 clusters with 226 cases confirmed cases RT-PCR Not reported No Not reported
Martinez-Fierro 2020 Mexico Cross-sectional
June-July 2020
Unclear 19 asymptomatic index cases; 81 contacts RT-PCR
Serology
Not reported No Not reported
Mponponsuo 2020 Canada Observational
Hospital
March-April 2020
Nosocomial 5 HCWs were index cases; 39 HCWs (16
underwent testing) and 33 patients were
exposed (22 underwent testing)
RT-PCR Not reported No Not reported All 5 HCWs had E gene cycle threshold (Ct) values between
10.9 and 30.2. Those exposed to the index HCWs were
followed for 30 days
Ng 2020 Singapore Retrospective cohort study
Various
January-April 2020
Household
Local
Community
1114 PCR-confirmed COVID-19 index cases
in the community in Singapore. 13 026
close contacts (1863 household, 2319
work, and 3588 social)
RT-PCR
Serology
If contacts reported symptoms No Not reported Lower risk contacts: Other contacts who were with the index
case for 10–30 min within 2 m
Contacts who reported symptoms were admitted to the
hospital for COVID-19 testing by PCR.
Ning 2020 China Observational study
Various
January-February 2020
Household
Local
Community
Local cases: 3,435 close contacts
Imported cases: 3,666 close contacts
Not reported Not reported No Not reported Imported cases, farmers' markets, malls and wildlife exposure
Njuguna 2020 USA Observational
Prison
May 2020
Local 98 incarcerated and detained persons RT-PCR Not reported No Not reported Unclear how many index or close contacts
Ogawa 2020 Japan Observational
Hospital
Nosocomial 1 index patient; 15 HCWs were contact RT-PCR
Serology
RT-PCR: 10th day after exposure
Serology: Before isolation
No Not specified Viral culture performed for only the index patient
Paireau 2020 France Retrospective observational
Various
January to March 2020
Household
Local
Nosocomial
735 index cases; 6,082 contacts RT-PCR Not reported No Not reported Family, home, work, hospital.
Index case: A case whose detection initiated an investigation
of its contacts through contact tracing
Only contacts who developed symptoms compatible with
COVID-19 were tested for SARS-CoV-2
Park 2020 S. Korea Retrospective observational
Various
February 2020
Local
Household
Community
2 index cases; 328 contacts RT-PCR 24 hrs for 37 first contacts;
others within 2 weeks
No <40 considered
positive
Aircraft, home, restaurant, clinic, pharmacy.
Contact tracing of COVID-19 cases was conducted from 1 day before symptom onset or 1 day
before the case was sampled.
Park 2020a S. Korea Observational study
Homes
January to March 2020
Household
Non-household
5,706 COVID-19 index patients; 59,073
contacts
Not reported Not reported No Not reported
Park 2020b S. Korea Observational study
Workplace, home
March 2020
Local
Household
216 employees, 225 household contacts RT-PCR Within 2 weeks of report of
infected case
No Not reported Employees do not generally go between floors, and they do
not have an in-house restaurant for meals.
Sent a total of 16,628 text messages to persons who stayed
>5 minutes near the building X; we tracked these persons by
using cell phone location data.
Passarelli 2020 Brazil Observational
Hospital
August 2020
Nosocomial 6 index cases; 6 close contacts RT-PCR Not reported No <40 considered
positive
All index cases were asymptomatic hospital visitors
Patel 2020 UK Retrospective observational
Hospital, community
March to April 2020
Household 107 cases; 195 household contacts RT-PCR Not tested No Not reported
Pavli 2020 Greece Observational contact tracing
Aircraft
February to March 2020
Aircraft 6 index cases; 891 contacts RT-PCR Not reported No Not reported A COVID-19 case was defined at that time as a case with
signs and symptoms compatible with COVID-19 in a patient
with laboratory-confirmed SARS-CoV-2 infection, recent travel
history to a country with evidence of local transmission of
SARS-CoV-2 or close contact with a laboratory-confirmed case
Phiriyasart 2020 Thailand Observational
Homes
April 2020
Household 471 household contacts RT-PCR Within 5 days of exposure No Not reported
Poletti 2020 Italy Observational
February-April 2020
Unclear 5,484 close contacts from clusters RT-PCR
Serology
Not reported No Not reported Only contacts belonging to clusters (i.e. groups of contacts
identified by one positive index case) were included.
1,364 (25%) were tested with only RT-PCR, 3,493 (64%) with
only serology at least a month after the reporting date of
their index case and 627 (11%) were tested both by RT-PCR
and serology.
Pung 2020 Singapore Observational
Various
February 2020
Local
Community
425 close contacts from 3 clusters; index
case unclear
PCR
WGS
Phylogenetic
analysis
Not reported No Not reported Company conference, church, tour group.
Close contacts under quarantine for 14 days from last
exposure to the individual with confirmed COVID-19, either at
home or at designated government quarantine facilities.
Pung 2020a Singapore Observational
Homes
Up till March 2020
Household 277 were primary or co‐primary cases: 875
household contacts
Not reported Not reported No Not reported Household contacts were tested if they showed symptoms of
SARS-CoV-2 infection, or if aged 12 years or below
Qian 2020 Hong Kong Observational retrospective
Various
January to February 2020
Local
Household
Community
Unclear Not reported Not reported No Not reported Homes, transport, restaurants, shopping and entertainment
venues.
Four categories of infected individuals were considered based
on their relationship: family members, family relatives, socially
connected individuals, and socially non‐connected individuals
Ravindran 2020 Indonesia Retrospective cohort
Wedding
March 2020
Local 41 guests; no. of index cases unclear RT-PCR Not reported No Not reported Primary case: Any person who attended the wedding events
in Bali Indonesia during 15–21 March 2020 and who tested
positive.
Secondary case: any person who tested positive on SARS-
CoV-2 after the 14 day period and who was a close contact of
a COVID-19 case from the wedding events.
Razvi 2020 UK Observational study
Hospital
May to June 2020
Nosocomial 2,521 HCWs Serology Voluntary first-come, first-served
basis
No N/A
Rosenberg 2020 USA Observational retrospective
Homes
March 2020
Household 229 cases; 498 household contacts RT-PCR Not reported No Not reported
Roxby 2020 USA Observational - cross-sectional
Nursing home
March 2020
Nosocomial 80 residents and 62 staff members; no
index case
RT-PCR Day 1 and 7 days late No No Residents isolated in their rooms; no communal meals or
activities, no visitors allowed in the facility, staff member
screening and exclusion of symptomatic staff members
implemented. Enhanced hygiene practices were put into
effect, including cleaning and disinfection of frequently
touched surfaces and additional hand hygiene stations in
hallways for workers to use. All residents were tested again
7 days later.
Sang 2020 China Case series
Home
February 2020
Household 1 index case; 6 family members Not reported Within 24 hrs of index case No Not reported Central air conditioner was always running at home
Schumacher 2020 Qatar Prospective cohort study
Football team
June to September 2020
Local 1337; no index cases RT-PCR
Serology
RT-PCR: Every 3–5 days
Serology: Every 4 weeks
No ≤30 positive Strict hygiene measures and regular testing.
Two phases, the quarantine phase (entry until exit) and the
training and match phase (after quarantine exit until the first
test done during the week after the last match. Ct >30 but
<40 reactive.
1337 subjects were tested at least once; however, some
players and staff joined their team and were gradually
included in (or left) the programme during the study period.
Schwierzeck 2020 Germany Observational
Hospital paediatric dialysis unit
Nosocomial 1 index case; 48 contacts RT-PCR 24 hrs after index case No Not specified Outbreak was defined as two or more COVID-19 infections
resulting from a common exposure
Shah 2020 India Observational
Homes
March to July 2020
Household 74 primary cases; 386 household contacts RT-PCR Not reported No Not reported
Shen 2020 USA Observational
Social gathering
January to February 2020
Household
Community
1 index case: 539 social and family contacts RT-PCR If contact had symptoms No Not specified
Sikkema 2020 Netherlands Cross-sectional
Hospital
March 2020
Nosocomial 1796 HCWs; index case not specified RT-PCR
WGS
Phylogenetic
analysis
N/A No <32 considered
positive
HCWs across 3 hospitals.
Son 2020 S. Korea Observational study
Homes
January to March 2020
Household 108 primary cases; 3223 contacts RT-PCR Unclear No Not reported
Song 2020 China Observational case series
Home
January 2020
Household 4 family clusters. 4 index cases: 18 close
contacts
RT-PCR 0 to 72 hrs after index case
tested positive
No Not reported
Speake 2020 Australia Observational retrospective
Aircraft
March 2020
Aircraft 241 passengers some of whom had
disembarked from 1 of 3 cruise ships that
had recently docked in Sydney Harbour. 6
primary cases initially
RT-PCR
WGS
Phylogenetic
analysis
Within 2 weeks of primary cases Yes Not specified Primary cases as passengers with SARS-CoV-2 who had been
on a cruise ship with a known outbreak in the 14 days before
illness onset and whose specimen yielded a virus genomic
sequence closely matching that of the ship’s outbreak strain
Secondary cases: Passengers with PCR-confirmed SARS-
CoV-2 infection who had not been on a cruise ship with a
known SARS-CoV-2 outbreak within 14 days of illness onset
and in whom symptoms developed >48 hours after and within
14 days of the flight; or international passengers who had
not been on a cruise ship in the 14 days before illness and
whose specimens yielded a WGS lineage not known to be in
circulation at their place of origin but that closely matched the
lineage of a primary case on the flight.
Stein-Zamir 2020 Israel Observational - cross-sectional
Schools
May 2020
Local 1,190 students aged 12–18 years (grades
7–12) and 162 staff members.
PCR Unclear No Not reported
Sugano 2020 Japan Observational retrospective
Music concerts
February 2020
Local 1 index case; 72 exposures RT-PCR Not reported No Not specified
Sun 2020 China Observational
Homes
Household Family clusters Not reported Not reported No Not reported
Taylor 2020 USA Observational
Skilled nursing facilities
April-June 2020
Nosocomial 259 tested residents, and 341 tested HCP RT-PCR
WGS
Phylogenetic
analysis
Weekly serial testing (every
7–10 days)
No Not specified
Teherani 2020 USA Observational
Homes
March to June 2020
Household 32 paediatric cases; 144 household
contacts
PCR Within 2 weeks of exposure to
infected case
No Not reported Only children who presented with symptoms concerning for
COVID-19 infection were included.
Thangaraj 2020 India Observational
Tourist group
February 2020
Community 1 index case; 26 close contacts RT-PCR Within 24 hrs of index case No Not reported
Torres 2020 Chile Cross-sectional
Community
March-May 2020
Community 1009 students and 235 staff Serology 8–10 weeks after school
outbreak
No N/A The school was closed on March 13, and the entire community
was placed in quarantine
Tshokey 2020 Bhutan Observational
Tourists
May 2020
Local
Community
27 index cases; 75 high-risk contacts, 1095
primary contacts; 448 secondary contacts
RT-PCR High-risk contacts: minimum of
three times with RT-PCR
No ≤ 40 considered
positive
van der Hoek 2020 Netherlands Observational
Household
March to April 2020
Household 231 cases; 709 close contacts. 54 families
have 239 participants, 185 of whom are
family members.
RT-PCR
Serology
Not reported No Not reported
Wang 2020 China Observational
Home
January-February 2020
Nosocomial
Household
25 HCWs, 43 family members RT-PCR
WGS
Phylogenetic
analysis
Not reported No Not reported
Wang 2020a China Retrospective observational
Home
February 2020
Household 85 primary cases: 155 household contacts
in 78 households
RT-PCR Not reported No <37 considered
positive
Wang 2020b China Retrospective cohort study
Homes
February to March 2020
Household 124 primary cases; 335 close
contacts
RT-PCR Within 2 weeks of symptom
onset of the primary case
No Not reported
Wee 2020 Singapore Observational
Tertiary Hospital
February to May 2020
Nosocomial 28 index cases; 253 staff close-contacts
and 45 patient close-contacts
RT-PCR If patient close-contacts or
staff close-contacts developed
symptoms
No Not specified Infection control bundle was implemented comprising
infrastructural enhancements, improved PPE, and social
distancing between patients. Patients were advised to wear
surgical masks, to remain within their room or cohorted
cubicle at all times, and to avoid mingling with each other.
Wendt 2020 Germany Observational
Hospital
March 2020
Nosocomial 1 index case physician; 187 contacts with
HCWs and 67 contacts with patients - 23
high-risk contacts in total
RT-PCR
Serology
5-days post exposure (5 & 10 days
post exposre for high-risk
contacts
No <36 or <39 considered positive All high-risk contacts and the index physician were examined
serologically on days 15 or 16 and days 22 or 23 after
exposure.
Wolf 2020 Germany Observational case series
Hospital quarantine
January-February 2020
Household Family cluster: 1 index case, 4 close
contacts
RT-PCR 5-days after index case tested
positive
No Not reported The parents were asked to wear masks; wearing masks was
not practical for the children.
Wong 2020 Hong Kong Observational
Hospital
February 2020
Nosocomial 1 index case in AIIR: 71 staff and 49 patients RT-PCR End of 28-day surveillance No Not specified
Wood 2020 UK Retrospective cohort
HCW homes
Household 241,266 adults did not share a household
with young children; 41,198, 23,783 and
3,850 shared a household with 1, 2 and 3
or more young children
PCR Not reported No Not reported Primary exposure was the number of children aged 0 to 11
years in each household.
Wu 2020 China Retrospective cohort study
Various
January-February 2020
Household
Local
Community
144 cases, 2994 close contacts Not reported Not reported No Not reported Shared transport, visit, medical care, household, brief contact.
Wu 2020a China Prospective observational
Homes
February to March 2020
Household 35 index cases; 148 household contacts Not reported Not reported No Not reported All consecutive patients with probable or confirmed COVID-
19 admitted to the Fifth Affiliated Hospital of Sun Yat-sen
University from 17 January to 29 February 2020 were enrolled.
All included patients and their household members were
interviewed
Xie 2020 China Cross-sectional
Home
January-February 2020
Household 2 family clusters with 61 residents (5 cases) RT-PCR 7 days after primary or index
cases diagnosed
No Not reported
Xin 2020 China Prospective cohort study
Homes
January to March 2020
Household 31 primary cases; 106 household contacts RT-PCR Not reported No Not reported
Yang 2020 China Observational cohort study
Home quarantine
February-May 2020
Household
Local
93 recurrent-positive patients; 96 close
contacts and 1,200 candidate contacts
RT-PCR
Serology
Within 14 days post-exposure Yes ≤ 40 considered
positive
Yau 2020 Canada Retrospective cohort study
Hospital dialysis unit
April 2020
Nosocomial 2 index cases; 330 contacts (237 patients
and 93 staff)
RT-PCR Not reported No Not reported All symptomatic contacts were referred for testing but
asymptomatic household contacts were not routinely tested
as per public health protocols at the time.
Ye 2020 China Observational
Religious gathering
January-February 2020
Local
Community
66 confirmed cases and 15 asymptomatic
infections: 1,293 close contacts
RT-PCR Not reported No Not reported All close contacts were quarantined
Yoon 2020 S. Korea Observational
Childcare Centre
February-March 2020
Local 1 index case: 190 persons (154 children
and 36 adults) were identified as contacts;
44 were defined as close contacts (37
children and 7 adults)
PCR 8–9 days after the last exposure No <37 considered positive Wearing masks, more frequent hand hygiene, and disinfection
of the environment were required before the child index case
tested positive.
Yousaf 2020 USA Survey: cross-sectional
Tertiary-care referral facility
June 8 to July 8, 2020
Household 198 household contacts; index cases not
specified
RT-PCR Day 1 of study No Not reported
Yu 2020 China Observational study
Homes
January to February 2020
Household 560 index cases; 1587 close contacts Not reported Within 2 weeks of exposure to
primary case
No Not reported Exposure environments included workplace, medical centre,
etc. Contact methods included eating or living together,
sleeping together, living in same house, etc
Yung 2020 Singapore Observational prospective
Homes
March to April 2020
Household 137 households, 213 paediatric contacts Not reported Unclear No Not reported
Zhang 2020 China Retrospective Observational
Aircraft
March-April 2020
Aircraft 4462 passengers screened for COVID-19
based on close contact
RT-PCR Not reported No Not reported All passengers were quarantined after arrival
Zhang 2020a China Retrospective observational
Various
January-March 2020
Household
Local
Community
359 cases: 369 close contacts Not reported Not reported No Not reported Households, social contact, workplace
Zhang 2020b China Observational study
Hospital
April 2020
Household 3 index cases; 10 close contacts RT-PCR
Serology
Not reported No <37 considered
positive
Ct value of 40 or more was defined as a negative test.
Zhang 2020c China Observational
Quarantine
January-February 2020
Local
Household
Multi-family cluster of 22 cases: 93 close
contacts
RT-PCR Not specified No Not reported All close contacts were quarantined in centralized facilities.
Zhang 2020d China Observational
Supermarket
January-February 2020
Local 1 index case: 8437 contacts RT-PCR Not reported No Not reported
Zhuang 2020 China Observational study
Various
January to February 2020
Household
Community
Cluster outbreaks; 8363 close contacts Not reported Not reported No Not reported Family and non-family cases

Table 2. Main characteristics of systematic reviews.

Study ID (n=9) Fulfils
systematic
review methods
Research question (search date up to) No. of included studies
(No. of participants)
Main results Key conclusions
Chen 2020 Yes To estimate seroprevalence by different types of
exposures, within each WHO
region, we categorized all study participants into
five groups:
1) close contacts,
2) high-risk healthcare workers,
3) low-risk healthcare workers,
4) general populations, and
5) poorly-defined populations
(Search from Dec 1, 2019 to Sep 25, 2020).
230 studies involving
1,445,028 participants were
included in our meta-analysis
after full-text scrutiny:
Close contacts 16 studies
2901 positives out of 9,349
participants
Estimated seroprevalence of all infections, 22.9% [95% CI,
11.1–34.7] compared to relatively low prevalence of SARS-
CoV-2 specific antibodies among general populations, 6,5%
(5.8–7.2%) see Appendix table 15 (page 152).
The overall risk of bias was low.
There were a very limited number of high-quality studies
of exposed populations, especially for healthcare
workers and close contacts, and studies to address
this knowledge gap are needed. Pooled estimates of
SARS-CoV-2 seroprevalence based on currently available
data demonstrate a higher infection risk among close
contacts and healthcare workers lacking PPE,
Chu 2020 Yes To investigate the effects of physical distance, face
masks, and eye protection on virus transmission in
health-care and non-health-care (eg, community)
settings (We searched up to March 26, 2020)
Identified 172 studies; 44
studies included in the
meta-analysis which 7 were
Covid-19
A strong association was found of proximity of the exposed
individual with the risk of infection (unadjusted n=10 736, RR
0·30, 95% CI 0·20 to 0·44; adjusted n=7782, aOR 0·18, 95% CI
0·09 to 0·38; absolute risk [AR] 12·8% with shorter distance
vs 2·6% with further distance, risk difference. There were six
studies on COVID-19, the association was seen irrespective of
causative virus (p value for interaction=0·49).
The risk of bias was generally low-to-moderate.
Physical distancing of at least 1 m is strongly associated
with protection, but distances of up to 2 m might be
more effective.
Fung 2020 Yes To review and analyze available studies of the
household SARs for SARS-CoV-2.
Searched PubMed, bioRxiv, and medRxiv on 2
September 2020 for published and prepublished
studies reporting empirical estimates of
household SARs for SARS-CoV-2.
Considered only English-language records posted
on or after 1 January 2019.
Inclusion criteria:
Reported estimates of the household SAR or the
data required to compute the household SAR; (2)
comprised data from more than 1 household; and
(3) they tested—at a minimum—all symptomatic
household contacts by reverse transcription
polymerase chain reaction (RT-PCR).
22 papers met the eligibility
criteria: 6 papers reported
results of prospective studies
and 16 reported retrospective
studies. The number of
household contacts evaluated
per study ranged from 11 to
10592.
The 22 studies considered 20 291 household contacts, 3151
(15.5%) of whom tested positive for SARS-CoV-2. Household
secondary attack rate estimates ranged from 3.9% in the
Northern Territory, Australia to 36.4% in Shandong, China.
The overall pooled random-effects estimate of SAR was 17.1%
(95% confidence interval [CI], 13.7–21.2%), with significant
heterogeneity (p<0.0001).
The household secondary attack rates was highest for index
cases aged 10–19 years (18.6%; 95% CI, 14.0–24.0%) and
lowest for those younger than 9 (5.3%; 95% CI, 1.3–13.7%).
4 of the studies were judges as high quality; 14 as moderate
quality; and 4 as low quality. Between-study variation could
not be explained by differences in study quality.
Secondary attack rates reported using a single follow-up
test may be underestimated, and testing household
contacts of COVID-19 cases on multiple occasions may
increase the yield for identifying secondary cases.
There is a critical need for studies in Africa, South Asia
and Latin America to investigate whether there are
setting-specific differences that influence the household
SAR.
Koh 2020 Yes The secondary attack rate (SAR) in household and
healthcare settings. Search between Jan 1 and
July 25, 2020.
118 studies, 57 were included
in the meta-analyses.
Pooled household SAR 18.1% (95% CI: 15.7%, 20.6%)
significant heterogeneity (p <0.001).
No significant difference in secondary attack rates in terms of
the definition of household close contacts, whether based on
living in the same household (18.2%; 95% CI: 15.3%, 21.2%)
or on relationships such as family and close relatives (17.8%;
95% CI: 13.8%, 21.8%)
In three studies, the household secondary attack rates of
symptomatic index cases (20.0%; 95% CI: 11.4%, 28.6%) was
higher than asymptomatic ones (4.7%; 95% CI: 1.1%, 8.3%)
SAR from 14 studies showed close contacts adults were more
likely to be infected compared to children (<18), relative risk
1.71 (95% CI: 1.35, 2.17).
43 high-quality studies were included for meta-analysis.
There was variation in the definition of household
contacts; most included only those who resided with
the index case, some studies expanded this to include
others who spent at least a night in the same residence
or a specified duration of at least 24 hours of living
together, while others included family members or close
relatives.
Li 2020 No (quality
assesment not
performed)
~Carriage and transmission potential of SARS-
CoV-2 in children in school and community
settings (Search performed on 21 June 2020
with entry date
limits from late 2019)
33 studies were included for
this review. Four new studies
on SARS-CoV-2 transmission
in school settings were identified.
There is a lack of direct evidence on the dynamics of child
transmission, however the evidence to date suggests that
children are unlikely to be major transmitters of SARS-CoV-2.
The balance of evidence suggests that children play
only a limited role in overall transmission, but it is noted
that the relative contribution of children to SARS-CoV-2
transmission may change with reopening of society and
schools
Ludvigsson 2020 No (quality
assesment not
performed)
Are children the main drivers of the COVID‐19
pandemic (Search to 11 May 2020)
47 full texts studied in detail. This review showed that children constituted a small fraction
of individuals with COVID‐19
Children are unlikely to be the main drivers of the
pandemic. Data on viral loads were scarce, but indicated
that children may have lower levels than adults,
Madewell 2020 Yes What is the household secondary attack rate for
severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2)? ( Searched through Oct 19, 2020)
single database assessed
54 studies with 77,758
participants
Household secondary attack rates was 16.6%; restricted index
cases to children (<18 years), lower SAR of 0.5%
Secondary attack rates for household and family contacts
3 times higher than for close contacts (4.8%; 95% CI, 3.4%-
6.5%; P < .001);
Estimated mean household secondary attack rates from
symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%)
higher than from asymptomatic or presymptomatic index
cases (0.7%; 95% CI, 0%-4.9%; P < .001), there were few
studies in the latter group.
Infection risk was highest for spouses, followed by nonspouse
family members and other relatives, all higher than other
contacts.
Estimated mean household secondary attack rates to
spouses (37.8%; 95% CI, 25.8%-50.5%) higher than to
other contacts (17.8%; 95% CI, 11.7%-24.8%). Significant
heterogeneity was found among studies of spouses
(I2 = 78.6%; P < .001) and other relationships (I2 = 83.5%;
P < .001).
Contact frequency with index case associated with higher
odds of infection,
At least 5 contacts during 2 days before the index case was
confirmed; at least 4 contacts and 1 to 3 contacts, or frequent
contact within 1 meter.
Secondary attack rates for households with 1 contact (41.5%;
95% CI, 31.7%-51.7%) higher than households with at least
3 contacts (22.8%; 95% CI, 13.6%-33.5%; P < .001) but not
different than households with 2 contacts (38.6%; 95% CI,
17.9%-61.6%).
There was significant heterogeneity in secondary attack
rates between studies with 1 contact (I2 = 52.9%; P = .049),
2 contacts (I2 = 93.6%; P < .001), or 3 or more contacts
(I2 = 91.6%; P < .001). Information was not available on
household crowding.
A total of 16 of 54 studies (29.6%) were at high risk of bias, 27
(50.0%) were moderate, and 11 (20.4%) were low.
Secondary attack rates were higher in households
from symptomatic index cases than asymptomatic
index cases, to adult contacts than to child contacts,
to spouses than to other family contacts, and in
households with 1 contact than households with 3
or more contacts. Our study had several limitations.
The most notable is the large amount of unexplained
heterogeneity across studies. This is likely attributable
to variability in study definitions of index cases and
household contacts, frequency and type of testing,
sociodemographic factors, household characteristics
(eg, density, air ventilation), and local policies (eg,
centralized isolation). The findings of this study suggest
that households are and will continue to be important
venues for transmission, even where community
transmission is reduced.
Xu 2020 Yes Evidence for transmission of COVID-19 by
children in schools ( search in MEDLINE up to
14 September 2020. Further hand-searched
reference lists of the retrieved eligible publications
to identify additional relevant studies). Included
children (defined as ≤18 years old) who were
attending school, and their close contacts (family
and household members, teachers, school
support staff) during the COVID-19 pandemic
11 studies were included: 5
cohort studies and 6 cross-
sectional studies.
Overall infection attack rate (IAR) in cohort studies: 0.08%,
95% CI 0.00%-0.86%. IARs for students and school staff were
0.15% (95% CI 0.00%-0.93%) and 0.70% (95% CI = 0.00%-
3.56%) respectively (p<0.01). Six cross-sectional studies
reported 639 SARS-CoV-2 positive cases in 6682 study participants
tested [overall SARS-CoV-2 positivity rate: 8.00%
(95% CI = 2.17%-16.95%). SARS-CoV-2 positivity rate was
estimated to be 8.74% (95% CI = 2.34%-18.53%) among
students, compared to 13.68% (95% CI = 1.68%-33.89%)
among school staff (p<0.01). Overall study quality was judged
to be poor with risk of performance and attrition bias
There is limited high-quality evidence to quantify the
extent of SARS-CoV-2 transmission in schools or to
compare it to community transmission. Emerging
evidence suggests lower IAR and SARS-CoV-2 positivity
rate in students compared to school staff.
Yanes-Lane 2020 Yes Proportion of asymptomatic infection among
coronavirus disease 2019 (COVID-19) positive
persons and their transmission potential. (Search
up to up to 22 June 2020)
28 moderate/high quality
studies included; 43 low
quality studies excluded
Asymptomatic COVID-19 infection at time of testing ranged
from 20% - 75%; among three studies in contacts it was 8.2%
to 50%. Asymptomatic infection in obstetric patients pooled
proprtion was 95% (95% CI, 45% to 100%) of which 59% (49%
to 68%) remained asymptomatic through follow-up;
Among nursing home residents, the proportion of
asymtomoatic was 54% (42% to 65%) of which 28% (13%
to 50%) remained asymptomatic through follow-up.
The proportion of asymptomatic infection among
COVID-19 positive persons appears high and
transmission potential seems substantial.
Zhu 2020 Meta-analysis:
Quality
assessment not
performed
Role of children in SARS-CoV-2 in household
transmission clusters ( Search between Dec,
2019 & Aug, 2020).
57 articles with 213 clusters 8 (3.8%) transmission clusters were identified as having
a paediatric index case. Asymptomatic index cases were
associated with lower secondary attack rates in contacts than
symptomatic index cases [RR] 0.17 (95% CI,0.09–0.29). SAR
in paediatric household contacts was lower than in adult
household contacts (RR, 0.62; 95% CI, 0.42–0.91).
The data suggest that should children become infected
at school during this period, they are unlikely to spread
SARS-CoV-2 to their co-habiting family members.

Quality of included studies

None of the included primary studies reported a published protocol except one (Helsingen 2020). The risk of bias of the included primary studies is shown in Table 5. Only 61 studies (35.7%) adequately reported the methods used, and 97 (56.7%) adequately described the sources of sample collection. Only six studies (3.5%) adequately reported methods used to address biases. The overall quality of the studies was judged as low to moderate (see the risk of bias graph in Figure 2).

Figure 2. Risk of bias graph in primary studies of close contacts in SARS-CoV-2.

Figure 2.

Reviews

We included 10 systematic reviews investigating the role of close contact in SARS-CoV-2 transmission ( Table 2). The studies included in the reviews were primarily observational. In one review (Chen 2020), there was a higher risk of infection in close contacts and healthcare workers without PPE compared to the general population. A second review (Chu 2020) found a significant association between proximity of exposure (distance <1m), absence of barriers (not using face covering or eye protection) and the risk of infection. The authors of three reviews (Li 2020, Ludvigsson 2020, Zhu 2020) concluded that children were unlikely to be the main conduit for transmission of SARS-CoV-2, and results of one review (Koh 2020) showed that adults with close contact exposure were significantly more likely to be infected compared with children (14 studies, RR: 1.71 (95% CI: 1.35, 2.17)). In one review (Xu 2020), the attack rates were significantly less in students compared with staff (p<0.01). One review (Fung 2020) reported household SARs ranging from 3.9% to 36.4%, but also highlighted the lack of SARS-CoV-2 research in Africa, South Asia, and Latin America. One review (Madewell 2020) found that SARs were higher in households from symptomatic index cases than asymptomatic index cases, and one review (Yanes-Lane 2020) concluded that the proportion of asymptomatic infection was high (20–75%). In two reviews (Koh 2020, Yanes-Lane 2020), studies judged to be of low quality were excluded from their meta-analyses. In one review (Chen 2020), the overall quality was reported as low, while 80% of included studies were reported as moderate or high quality in another two (Fung 2020, Madewell 2020). Another review (Chu 2020) reported the overall risk of bias as low-to-moderate, and one (Xu 2020) rated the overall quality as low. Three reviews did not assess study quality (see Table 2).

Primary studies

We found 171 primary studies ( Table 1). In general, the studies did not report any hypothesis but assessed epidemiological or mechanistic evidence for transmission associated with close contact settings. Ninety-three studies (54.4%) were conducted in Asia, 43 (25.1%) in Europe, 27 (15.8%) in North America, five (2.9%) in South America and three (1.8%) in Australasia. The study settings included home/quarantine facilities (n=54), hospital (n=26), social/religious gatherings (n=13), public transport (n=7) care homes (n=4), and educational settings (n=8). Thirteen studies used two settings (home plus one other setting). In 25 studies (15.2%), the settings were multiple (3 or more different settings). Two studies were conducted in professional sports settings: one Super League Rugby (Jones 2020) and one football team (Schumacher 2020)

All the included studies were observational in design except one RCT (Helsingen 2020): 24 studies were described as cohort, nine were case series and 12 cross-sectional. One study used a before and after study design. The number of close contact participants included ranged from 4 to 8437. Three studies (Chen 2020a, Hong 2020, Yang 2020) examined transmission dynamics in close contacts of index or primary cases with recurrent SARS-CoV-2 infections.

Eighty-two studies (46.8%) reported definitions of close contacts ( Table 3). There was a variation in the definitions across the studies. Seventeen studies (9.9%) defined close contact as exposure to the index or primary case within two metres for at least 15 minutes while four defined it as being within 2m for at least 10 minutes. In 24 studies, there was no specified distance reported - close contact definitions included unprotected exposure, living in the same household or bedroom, sharing a meal, or having repeated and prolonged contact. In five studies of airline passengers, close contact was defined as all passengers on the flight (Chen 2020), seated within two rows of the index case (Draper 2020, Pavli 2020, Speake 2020), or being within 2m for at least 15 minutes (Khanh 2020). Eighty-seven studies (50.9%) did not define close contact and the definition was unclear in four studies. Twenty-nine studies (17%) defined other types of contacts including primary contact, secondary contact, high-risk contact, household contact, social contact, and work contact (see Table 3).

Table 3. Definitions and descriptions of close contacts.

Study ID Definitions of close contacts Definition of other contacts Contact duration & proximity
Abdulrahman 2020 Not defined Not reported Not reported
Adamik 2020 Not defined Other cases in each of the infected households were
regarded as secondary cases
Not reported
Agergaard 2020 Not defined Not reported 2 weeks
Angulo-Bazán 2020 Not defined Not reported Not reported
Armann 2020 Not defined Not reported Not reported
Arnedo-Pena 2020 Close contacts living in the same household of the index case and no other
sources of transmission apart from the index case could be found.
Closed contacts from work, social events, relatives live
in other household were excluded and index cases live alone.
Not reported
Baker 2020 Not defined Not reported Median cumulative time spent with the patient 45 mins
(10–720 mins)
Baettig 2020 Close contact: Less than 2 m for more than 15 min in the last 48 hours before
onset symptom of the COVID-19 positive index patient.
Not reported <2m for >15 mins 48 hours before onset symptom of the
COVID-19 positive index patient
Bao 2020 Not defined Not reported Average stay duration of 2.5 hr daily before the COVID‐19
outbreak.
Basso 2020 Close contact: ≥15 min at ≤2 m, or during AGPs, between HCWs and the non-
isolated COVID-19 patient
Not reported ≤2 m for ≥15 min or during AGP
Bays 2020 Not defined Not reported Not specified
Bi 2020 Close contacts were identified as those who lived in the same apartment,
shared a meal, travelled, or socially interacted with an index case 2 days before
symptom onset.
Casual contacts (eg, other clinic patients) and some
close contacts (eg, nurses) who wore a mask during
exposure were not included in this group.
Not specified
Blaisdell 2020 Not defined Not reported 1 week
Böhmer 2020 High risk if they had cumulative face-to-face contact with a patient with
laboratory-confirmed SARS-CoV-2 infection for at least 15 min, had direct contact
with secretions or body fluids of a patient with confirmed COVID-19, or, in the
case of health-care workers, had worked within 2 m of a patient with confirmed
COVID-19 without PPE
All other contacts were classified as low-risk contacts. Face-to-face for at least 15 minutes, direct contact without
PPE
Boscolo-Rizzo 2020 Not defined Not reported Not reported
Brown 2020 Not defined Not reported Mean in-class time = 50 minutes
Burke 2020 Either at least 10 minutes spent within 6 feet of the patient with confirmed
COVID-19 (e.g., in a waiting room) or having spent time in the same airspace
(e.g., the same examination room) for 0–2 hours after the confirmed COVID-19
patient.
Not reported Within 6 feet for at least 10 minutes
Canova 2020 Not defined Not reported 5 HCWs: >30 minutes
5 HCWs: >15–30 mins
6 HCWs: 5–15 mins
5 HCWs: ≤5 mins
Cariani 2020 Not defined Not reported Not reported
Charlotte 2020 Not defined Not reported 2-hours
Chaw 2020 Close contact: Any person living in the same household as a confirmed case-
patient or someone who had been within 1 m of a confirmed case-patient in an
enclosed space for >15 minutes
Not reported Within 1m for >15 mins
Chen 2020 Close contact: All passengers were regarded as close contacts Not reported Flight duration 5 hours approx
Chen 2020a Close contacts are persons who have had close contact with re-positive patients
without effective protection with masks, such as living and working together
Not reported Not specified
Chen 2020b Not defined Not reported Not specified
Chu 2020 Community contact: Any close contact (being within 6 feet of the case-patient)
for a prolonged time (>10 minutes); being an office co-worker of the case-patient
with close contact of any duration; contact with infectious secretions from the
case-patient; or sharing a healthcare waiting room or area during the same time
and up to 2 hours after the case-patient was present.
Healthcare contact: Face-to-face interaction between
healthcare personnel (HCP) and the case-patient
without wearing the full PPE that was recommended at
the time of the investigation or potential contact with the
case-patient’s secretions by HCP without wearing
full PPE.
>10 mins to 2 hours
Chen 2020c Not defined Not reported Not reported
Cheng 2020 Close contact was a person who did not wear appropriate PPE while having
face-to-face contact with a confirmed case for more than 15 minutes during the
investigation period. A contact was listed as a household contact if he or she
lived in the same household with the index case. Those listed as family contacts
were family members not living in the same household.
For health care settings, medical staff, hospital workers, and other patients in the
same setting were included; close contact was defined by contacting an index
case within 2 m without appropriate PPE and without a minimal requirement of
exposure time
Those listed as family contacts were family members
not living in the same household.
Within 2 m without PPE, face-to-face contact for >15
minutes
Chu 2020a Not defined Not reported Stayed ≥1 night in the household during case’s infectious
period
Contejean 2020 Close contact: Distance <2 meters for >10 minutes was defined as close contact Not reported <2 metres for >10 minutes
COVID-19 National Emergency Response Center 2020 Close contact (or high risk exposure)” was being within 2 meters of a COVID-19
case
Daily contact (or low risk exposure) was defined as
having proximity with a person who was a confirmed
COVID-19 case, without having had close contact.
Not reported
Danis 2020 All children and teachers who were in the same class as the symptomatic pediatric
case were considered as high risk contacts and were isolated at home.
Moderate/high risk: Person who had prolonged (> 15 min) direct face-to-face
contact within 1 m with a confirmed case, shared the same hospital room, lived
in the same household or shared any leisure or professional activity in close
proximity with a confirmed case, or travelled together with a COVID-19 case in
any kind of conveyance, without appropriate individual protection equipment.
Low risk: Person who had a close (within 1 m) but
short (< 15 min) contact with a confirmed case, or a
distant (> 1 m) but prolonged contact in public settings,
or any contact in private settings that does not match
with the moderate/high risk of exposure criteria.
Negligible risk: Person who had short (< 15 min)
contact with a confirmed case in public settings such
as in public transportation, restaurants and shops;
healthcare personnel who treated a confirmed case
while wearing appropriate PPE without any breach
identified.
4 days in chalet
Dattner 2020 Not defined Not reported Not reported
de Brito 2020 Close contact: Close and prolonged contact in the same room Not reported Not specified
Deng 2020 Not defined Not reported Not reported
Desmet 2020 Not defined Not reported Not reported
Dimcheff 2020 Close contact: Within 2 m or 6 feet) with an individual with confirmed COVID-19
for >15 minutes with the example being exposed to a family member at home
who has had a positive COVID-19 nasal swab
Not reported Within 2m for >15 mins
Dong 2020 Not defined Not reported Not reported
Doung-ngern 2020 High-risk if they were family members or lived in the same household as a
COVID-19 patient, if they were within a 1-meter distance of a COVID-19 patient
longer than 15 minutes; if they were exposed to coughs, sneezes, or secretions
of a COVID-19 patient and were not wearing protective gear, such as a mask; or if
they were in the same closed environment within a 1-meter distance of a COVID-
19 patient longer than 15 minutes and were not wearing protective gear
Not reported <15 min vs >15 min, <1m vs >1m
Draper 2020 Close contact was defined as anyone who had face-to-face contact with a
confirmed COVID-19 case for more than 15 minutes cumulatively or continuously
(e.g. household setting or healthcare setting without appropriate use of personal
protective equipment) or who was in the same room with an infectious case for
more than 2 hours (e.g. school room, workplace) while a case was symptomatic
or during the 24 hours preceding symptom onset. Aircraft close contacts
included passengers seated in the same row as, or in the two rows in front of
or behind, an infectious case. If the case was a crew member, the passengers
in the area in which the crew member worked were classified as close contacts.
Passengers disembarking from cruise ships with high incidence of COVID-19
were also classified as close contacts for surveillance purposes.
Not reported Not reported
Dub 2020 Close household contact, i.e. an individual sharing the main residence of the
secondary case
A regular household contact, i.e. an individual who
would regularly host or stay in the same residence of a
secondary case (step-sibling, divorced parent and new
partner).
Extended contact, i.e. an individual who would have
frequent contact with the secondary case around
and after the exposure, for example, grandparents
who were involved in caring of the secondary case,
according to parents’ reports.
<2 meters for >10 minutes
Expert Taskforce 2020 Close contact: Cabinmates of confirmed case-patients Not reported Not specified
Fateh-Moghadam 2020 Contact of a COVID-19 case has been considered any person who has had
contact with a COVID-19 case within a time frame ranging from 48 hours before
the onset of symptoms of the case to 14 days after the onset of symptoms
Not reported Not reported
Firestone 2020 Close contact: Being within 6 feet of a patient with laboratory-confirmed COVID-
19 infection for ≥15 minutes
Not reported Within 2m for >15 mins
Fontanet 2020 Not defined Not reported Not reported
Fontanet 2020a Not defined Not reported Not reported
Gan 2020 Not defined Not reported Not reported
Ghinai 2020 Not defined Not reported Not reported
Gong 2020 Close contact: Anyone who was closely in contact with a suspected, confirmed
and asymptomatic case without effective personal protection (classified
protection according to the contact situation, including gloves, medical protective
masks, protective face screens, isolation clothing, etc.) since onset of symptoms
in the suspected case and confirmed case or the day asymptomatic case’s
specimens were collected. The close contact included: (i) living, working, or
studying in one house or classroom, (ii) diagnosing, treating, or visiting cases
in hospital ward, (iii) being within short distance in the same vehicle, (iv) other
situations assessed by the field investigators.
Not reported Not reported
Gu 2020 Not defined Not reported 5 hrs, no natural ventilation or face masks;
distance between each other <0.5 m
Hamner 2020 Close contact: Within 6 feet of infected case Not reported 2.5 hrs within 2 m
Han 2020 Close contact: Travel was defined as someone who was in close contact with
a confirmed case for over three hours as they traveled to another region aside
from Region A. Close contact: meal was defined as someone who was in close
contact with a confirmed case for over 30 minutes after having a meal together.
A casual contact was defined as someone who spent
several minutes with a confirmed case within the
same space without any mask on (or a person was
established as a contact by an Epidemic intelligence
Officer).
30 mins to 3 hours
Heavey 2020 Close contact: Any individual who has had greaterthan 15 minutes face-to-face
(<2 meters distance*) contact with a case, in any setting.
Casual contact: Any individual who has shared a closed
space with a case for less than two hours.
Up to 2 hours in duration
Helsingen 2020 Not defined Not reported Not reported
Hendrix 2020 Not defined Not reported Not reported
Hirschman 2020 Close contact: Within 6 feet of an infected person for at least 15 minutes
starting from 2 days before illness onset.
Not reported "Hours"
Hobbs 2020 Close contact: Within 6 feet for ≥15 minutes) with a person with known COVID-
19, school or child care attendance, and family or community exposures ≤14 days
before the SARS-CoV-2 test
Not reported Within 2 m for ≥15 minutes
Hoehl 2020 Not defined Not reported Not reported
Hong 2020 Anyone who ever came within 2 m of a diagnosed patient without the use of
effective personal protective equipment
Not reported 258 person-days
Hu 2020 Close contacts were defined as individuals who had close-proximity interactions
(within 1 meter) with clinically suspected and laboratory-confirmed SARS-CoV-2
cases, for the period from 2 days before, to 14 days after, the potential infector’s
symptom onset. For those exposed to asymptomatic subjects, the contact
period was from 2 days before, to 14 days after, a respiratory sample was taken
for real-time RT-PCR testing. Close contacts included, but were not limited to,
household contacts (i.e., household members regularly living with the case),
relatives (i.e., family members who had close contacts with the case but did not
live with the case), social contacts (i.e., a work colleague or classmate), and other
close contacts (i.e., caregivers and patients in the same ward, persons sharing
a vehicle, and those providing a service in public places, such as restaurants or
movie theatres)
Not reported Not reported
Hua 2020 Not defined Not reported
Huang 2020 Close contacts quarantined at home or hospital Not reported Not reported
Huang 2020a Not defined Not reported Not reported
Islam 2020 Close contact was defined as individuals who were closely linked by contact
tracing and were considered a close contact group provided that no PPE was
worn having direct face to face contacts.
Household contacts were defined as individuals who
lived and were sharing the same room and same
apartment in the same household. Family contacts
were those who are the members of the same family
but not living in the same household.
Face-to-face
Jia 2020 A close contact was defined as a person who did not take effective protection
against a suspected or confirmed case 2 d before the onset of symptoms or an
asymptomatic infected person 2 d before sampling.
Not reported Not reported
Jiang 2020 Close contacts: Lived with the patients and individuals who had contact with
the patients within 1 meter without wearing proper personal protection. Ct value
≥40 was considered negative. The maximum likelihood phylogenetic tree of the
complete genomes was conducted by using RAxML software with 1000 bootstrap
replicates, employing the general time-reversible nucleotide substitution mode
Not reported 1 m
Jing 2020 A close contact was defined as an individual who had unprotected close
contact (within 1 m) with a confirmed case within 2 days before their symptom
onset or sample collection. Individuals who were linked by contact tracing were
considered a close contact group
Not reported Not reported
Jing 2020a Not defined Not reported Not reported
Jones 2020 Close contacts were defined by analysis of video footage for player interactions
and microtechnology (GPS) data for proximity analysis.
Not reported Within 1 m, face-to-face for ≥3 secs
Kang 2020 Not defined Not reported Not reported
Kant 2020 Not defined Not reported Not reported
Kawasuji 2020 Not defined Not reported Not reported
Khanh 2020 Close contact: <2 m distance for >15 minutes. Successfully traced passengers
and crew members were interviewed by use of a standard questionnaire, tested
for SARS-CoV-2
Not reported <2 m distance for >15 minutes.
Kim 2020 Not defined Household contact: Occurring at least 1 day after but
within 14 days from the last point of exposure.
2 days during the presymptomatic period and 1 day during
the symptomatic period of the index case.
Kim 2020a Not defined Not reported 2 hrs to 4 days
Kim 2020b Contact was defined as presence in the same room with COVID-19 confirmed
patients, or in the same outpatient clinic or examination room, 30 minutes before
and after COVID-19 confirmed patients. Within 2 m of confirmed patients (via
CCTV)
Not reported Within 2 m of confirmed patients for 30 mins
Kumar 2020 Not defined Not reported Not reported
Kuwelker 2020 Not defined Household members were defined as individuals who
resided in the same household as the index case.
Not reported
Kwok 2020 Close contacts referred to anyone who: (i) provided care to the case (including
a family member or healthcare worker) or had other close physical contact; or
(ii) stayed at the same place (including household members or visitors) while the
case was ill.
Not reported Not reported
Ladhani 2020 Not defined Not reported Not reported
Ladhani 2020a Not defined Not reported Not reported
Laws 2020 Not defined Not reported Unclear
Laxminarayan 2020 High-risk contacts had close social contact or direct physical contact with index
cases without protective measures
High-risk travel exposures—defined as close proximity to an infected individual in
a shared conveyance for ≥6 hours
Low-risk contacts were in the proximity of index cases
but did not meet criteria for high-risk exposure
Not reported
Lee 2020 Not defined: Frequent close contact Not reported >1 m
Lee 2020a Close contact (household contact) Not reported Mean contact period was calculated to be 7.7 days.
Lewis 2020 Not defined Household contacts were defined as all persons living
in the same household as the primary patient.
Not reported
Li 2020 Not defined Not reported Unclear
Li 2020a Not defined Not reported Not reported
Li 2020b Close contact was defined as an act of sharing a meal, party, vehicle or living
room with a confirmed or latently infected patient within 14 days.
Not reported Not reported
Li 2020c Close contacts were mainly those who have not take effective protection from
close contact with the suspected and confirmed cases 2 days before symptoms
appeared, or the asymptomatic infected persons 2 days before the specimen
collection.
Not reported Not reported
Li 2020d Not defined Not reported Not reported
Liu 2020 Not defined Not reported Unclear
Liu 2020a Direct contact with patients with neo-coronary pneumonia (within 1 m) Not reported Within 1m for 2.5 hrs
Liu 2020b Close contacts were defined by the China Prevention and Control Scheme of
COVID-19.
Not reported 7.8 (95%CI: 7.0–8.7) close contacts per index case.
Liu 2020c Not defined Not reported Not reported
López 2020 Close contact: Anyone who was within 6 feet of a person with COVID-19 for at
least 15 minutes ≤2 days before the patient’s symptom onset.
Not reported ≤1.83m of a person with COVID-19 for at least 15 minutes
≤2 days before the patient’s symptom onset
Lopez Bernal 2020 Household contacts were defined as those living or spending significant time in
the same household.
Household contacts, others with direct face to face contact and healthcare
workers who had not worn recommended PPE
Not reported Not reported
Lucey 2020 Close contact: HCW or patient who spent more than 15 minutes face-to-face
within 2 metres of a confirmed case or patients who shared a multi-bedded room
with a confirmed case for more than 2 hours.
Not reported Not reported
Luo 2020 Unclear: The tour coach was with 49 seats was fully occupied with all windows
closed and the ventilation system on during the 2.5-hour trip.
Not reported 1 to 4.5m; up to 2.5 hours on a bus
Luo 2020a Close contacts: Anyone who has had contact, without effective protection
regardless of duration of exposure, with 1 or more persons with suspected
or confirmed COVID-19 any time starting 2 days before onset of symptoms
in persons with a suspected or confirmed case, or 2 days before sampling for
laboratory testing of asymptomatic infected persons.
Not reported Not reported
Lyngse 2020 Not defined Not reported Not reported
Ma 2020 Not defined Not reported Longest contact time: 8 days
Shortest contact time: 0 days
Macartney 2020 Close contacts: Children or staff with face-to-face contact for at least 15 min,
or who shared a closed indoor space for at least 40 min with a case during their
infectious period.
Not reported Face-to-face contact for at least 15 min, or who shared a
closed indoor space for at least 40 min
Malheiro 2020 Close contacts (high risk)were defined as individuals who have spent 15 min or
more in closeproximity (2 m or less) to, or in a closed space with, a case.
Not reported Not reported
Maltezou 2020 Close contact was defined as a contact of >15 minutes within a distance of <2 m
with a COVID-19 case.
Household members were defined as persons living in
the same residence.
>15 minutes within <2 m
Maltezou 2020a Close contact was defined as a contact of >15 minutes within a distance of <2
meters with a COVID-19 case
Household contacts were defined as persons either
living in the same residence or having close contacts
with a family member for >4 hours daily in the family
residence.
Household: >4 hours daily
Close contact: >15 minutes within <2 m
Mao 2020 Not defined Not reported Not reported
Martinez-Fierro 2020 Individual who has had closer than <6 feet for ≥15 min with people with
a positive diagnosis for COVID-19, whether they were symptomatic or
asymptomatic according to the CDC definition
Not reported ≥15 min at a distance of <1.83m
Mponponsuo 2020 An interaction of >15 minutes at a distance of <1 m Not reported >15 minutes at a distance of <1 m
Ng 2020 Close contacts were individuals who had contact for at least 30 min within a 2 m
distance from the index case.
Work contacts were defined as individuals who came
into close contact with the index case at work, from 2
days before the onset of symptoms to isolation of the
case, to account for pre-symptomatic transmission.
Social contacts were defined as individuals who
came into close contact with the index case, from 2
days before onset of symptoms to isolation of the
case, through social activities. Transport contacts were
excluded
Lower risk contacts: Other contacts who were with
the index case for 10–30 min within 2 m
At least 30 min within a 2 m
Ning 2020 Not defined Not reported Unclear
Njuguna 2020 Not defined Not reported Unclear
Ogawa 2020 Not defined Not reported Not reported
Paireau 2020 Not defined Not reported Not reported
Park 2020 Not defined Not reported Not reported
Park 2020a High-risk contact (household contacts of COVID-19 patients, healthcare
personnel)
Household contact was a person who lived in the
household of a COVID-19 patient and a nonhousehold
contact was a person who did not reside in the same
household as a confirmed COVID-19 patient.
Not reported
Park 2020b Not defined Not reported Not reported
Passarelli 2020 Not defined Not reported Not reported
Patel 2020 Not defined Not reported Not reported
Pavli 2020 Close contacts were defined as persons sitting within a distance of <2 m for >15 min,
including passengers seated two seats around the index case and all crew
members and persons who had close contact with the index case.
Not reported <2 m for >15 min
Phiriyasart 2020 Close contact was defined as a person who had at least one of these following
criteria : (i) a person who came into close (within 1 meter) contact with, or had
a conversation with any patient for >5 minutes, or was coughed or sneezed
on by any patient when he/she did not wear appropriate personal protective
equipment (PPE), e.g. a face mask, (ii) a person who was in an enclosed space
without proper ventilation, e.g. in the same air-conditioned bus/air-conditioned
room as any patient , and was within one meter of any patient for >15 minutes
without wearing appropriate PPE.

High-risk close contact was defined as a close contact who was likely to contract
the virus from any patient through exposure to respiratory secretions of any
patient while not wearing PPE according to standard precautions.
A low-risk close contact was defined as a close contact
who was less likely to contract the virus from any
patient. This includes close contacts who have not met
the definition for high-risk close contacts.
Not reported
Poletti 2020 Not defined Not reported Not reported
Pung 2020 Close contacts: People who spend a prolonged time within 2 m of a confirmed
case
Other contacts: People who had some interactions
with the case.
Unclear
Pung 2020a Unclear: Close household contacts Not reported Unclear
Qian 2020 Four categories of infected individuals were considered based on their
relationship: family members, family relatives, socially connected individuals, and
socially non‐connected individuals
Not reported Not reported
Ravindran 2020 Close contact: Face-to-face contact for greater than 15 minutes cumulative in
the period extending from 48 hours before onset of symptoms in a confirmed
case; or sharing of closed space with a confirmed case for a prolonged period
of time in the period extending from 48 hours before onset of symptoms in a
confirmed case.
Not reported Face-to-face contact for at least 15 min, or who shared a
closed indoor space for prolonged period 48 hrs before
onset of symptoms
Razvi 2020 Not defined Not reported Not reported
Rosenberg 2020 Not defined Not reported
Roxby 2020 Not defined Not reported Not reported
Sang 2020 Not defined Not reported Not reported
Schumacher 2020 Close contact: Approximately 30–90 seconds in close proximity (<1.5 m) of other
players
Close social contacts (including sharing a car) 30–90 seconds in close proximity (<1.5 m)
Schwierzeck 2020 Not defined Not reported Not reported
Shah 2020 Household contact was defined as contact sharing same residential address. Not reported Not reported
Shen 2020 Close contacts defined as individuals who had close, prolonged, and repeated
interactions with the 2 source cases (Cases 2 and 3).
All other contacts are defined as casual contacts. Not reported
Sikkema 2020 Not defined Not reported Not reported
Son 2020 Not defined A contact was defined as anyone who was in contact
with a confirmed case from a day before the symptoms
occurred, in a manner that offered the potential for
transmission through respiratory droplets
Not reported
Song 2020 Unclear: shared the same bedroom, had dinner together Not reported Not reported
Speake 2020 2 rows in front and behind infectious passenger on an airplane Not reported Unclear
Stein-Zamir 2020 Not defined Not reported Not reported
Sugano 2020 Not defined Not reported Unclear
Sun 2020 Not defined Not reported Not reported
Taylor 2020 Not defined Not reported Unclear
Teherani 2020 Household contacts (HCs) were defined as an adult ( 18 years) or a child (<18
years) who resided in the home with the SIC at the time of diagnosis.
Not reported Not reported
Thangaraj 2020 Not defined Not reported Unclear
Torres 2020 Not defined Not reported Unclear
Tshokey 2020 Unclear: Close friends, roommates, flight seat partner, spouse or partner, cousin,
physician, tour driver
Primary contacts: Individuals coming in some form of
contact with the confirmed cases such as conveyance
in the same cars/flights, encounter in clinics, serving
meals, or providing housekeeping services in hotels.
Secondary contacts: Individuals coming in contact
with the primary contacts
Unclear
van der Hoek 2020 Not defined Not reported
Wang 2020 Not defined Not reported Unclear
Wang 2020a Not defined Not reported Unclear
Wang 2020b Close contact was defined as being within 1 m or 3 feet of the primary case, such
as eating around a table or sitting together watching TV.
Not reported Unclear
Wee 2020 Not defined Not reported Within 2 m of the index case for a cumulative time of ≥15
minutes, or who had performed AGPs without appropriate
PPE.
Wendt 2020 High-risk contacts: >15 min face-to-face contact, sitting in a row behind
physician for 45 mins, transfer in an ambulance (45-min drive).
Not reported >15 min face-to-face contact
Wolf 2020 Not defined Not reported Not specified
Wong 2020 Contact case was defined as a patient or staff who stayed or worked in the same ward as the
index patient. Patients who shared the same cubicle with the
index case were considered as ‘patient close contact’.
Staff close contact: Staff who had contact within 2 m of the index case for a
cumulative time of >15 min, or had performed AGPs, without ‘appropriate’ PPE.
Casual contacts: All staff and patients who did not fulfill
the pre-defined criteria for close contacts.
Casual/low-rosk contact: HCW wearing a facemask
or respirator only and have prolonged close contact
with a patient who was wearing a facemask, or HCW
using all recommended PPE or HCW (not using all
recommended PPE) who have brief interactions with
a patient regardless of whether patient was wearing a
facemask.
Patient close contacts were quarantined into an AIIR (or
quarantine camp if the patient was deemed clinically
stable to be discharged from hospital) for 14 days.
Within 2 m of the index case for a cumulative time of >15
min
Wood 2020 Not defined Not reported Not reported
Wu 2020 Close contact: Been within 1 metre of a confirmed case, without effective PPE,
within the period since 5 days before the symptom onset in the index case or
since 5 days before sampling if the index case was asymptomatic.
Not reported Within 1 metre of a confirmed case, without effective PPE
Wu 2020a Household contacts were defined as person who spent at least 1 night in the
house after the symptom onset of the index patient. A household was defined
as ≥2 people living together in the same indoor living space. A household index was
the first person to introduce SARS-CoV-2 into the household.
Not reported At least 1 night
Xie 2020 Close contact: An individual who has not taken effective protection when in
proximity of suspected or confirmed cases 2 days before the onset of symptoms
or 2 days before the collection of asymptomatic specimens.
Not reported Unclear
Xin 2020 Close contacts were defined as persons who had a short‐range contact history
for 2 days before the onset of symptoms in COVID‐19‐suspected and ‐confirmed
cases, or 2 days before the collection of samples from asymptomatic cases
without taking effective protective measures, such as family members in the
same house, direct caregivers, and medical staff who provided direct medical
care, colleagues in the same office or workshop, etc.
The effective contact duration for the close contacts
was defined as the contact days with index patients
with confirmed COVID‐19, which was calculated as the
last contact date minus the start contact date, and all
dates were corresponding to the definition of close
contacts
The median effective contact duration with patients
with COVID‐19 was 4 (IQR: 1–6) days, with 57 (53.8%)
experiencing effective contact between 3 and 11 days, and
9 (8.5%) with effective contact duration > 11 days
Yang 2020 Close contacts: Uunprotected exposure. Candidate contacts: Teachers and classmates Not reported
Yau 2020 Close unprotected contact with someone who has tested positive for COVID-19
in the last 14 days
Not reported Unclear
Ye 2020 Not defined Not reported Not reported
Yoon 2020 Close contact was defined as a person who had face-to-face contact for >15
minutes or who had direct physical contact with the index case-patient. Persons
who used the same shuttle bus were also considered to be close contacts.
Not reported Face-to-face contact for >15 minutes or direct physical
contact
Yousaf 2020 Not defined Not reported Not reported
Yu 2020 Close contacts were defined as those who lived in the same household, shared
meals, traveled or had social interactions with a confirmed case two days before
the onset of COVID-19 symptoms
Not reported Not reported
Yung 2020 Not defined Not reported Not reported
Zhang 2020 Not defined Not reported Not reported
Zhang 2020a Close contact: Refers to a person who had contact with index case without
using proper protection during 2 days before the index case was tested.
Not reported Not reported
Zhang 2020b Not defined Not reported Not reported
Zhang 2020c Close contacts were individuals who lived with a PCR-confirmed case or
interacted with a case within 1 metre from the case without any personal
protections.
Not reported Within 1m of case
Zhang 2020d Not defined Not reported Not reported
Zhuang 2020 Not defined Not reported Not reported

Eighteen studies (10.5%) reported data on the contact duration between close contacts and the index or primary cases ( Table 3). The average contact duration ranged from 30 minutes to 8 days across 16 studies that investigated transmission rates using RT-PCR. In two studies that examined transmission using serology (Agergaard 2020, Hong 2020), the durations of contact were two weeks and 258 person-days, respectively. The mean contact duration was either unclear or not reported in 148 studies (90.2%).

A total of 110 studies (64.3%) used RT-PCR as a test method for confirming SARS-CoV-2 positivity, while eight studies (4.8%) exclusively investigated transmission using serology. In 24 studies (14%), both PCR and serology were used to investigate close contact in SARS-CoV-2 transmission. Thirty-one studies (18.1%) did not report the test method used. For PCR, the timing of sample collection varied from within 24 hours to 14 days after exposure to the index or primary case; for serology, this ranged from 2–10 weeks post-exposure. In total, 71 studies (41.5%) reported the timing of sample collection. The timing of sample collection was either not reported or unclear in 100 studies (58.5%).

Twenty-two studies (12.9%) reported Ct values for determining PCR test positivity: ≤40 (eight studies), <37 (five studies), ≤35 (three studies), <38 (two studies), one each for <25, ≤30, <32 and <36 (or 39). Only eight studies reported the Ct values for close contacts in their results – these ranged from 16.03 to 38.

Thirty-two studies reported conducting serological tests to assess transmission of SARS-CoV-2 ( Table 4). There was variation in the description of the tests. Fifteen studies determined the antibody responses to SARS-CoV-2 spike proteins using Immunoglobulin G (IgG) and IgM while 11 used only IgG. In 17 studies, the threshold for serological positivity was not reported. Three studies (Kuwelker 2020, Ng 2020, Yang 2020) performed neutralisation assays to confirm positive serologic samples. In one study (Torres 2020), study participants self-administered the serological tests.

Table 4. Description of serological tests in close contact studies of SARS-CoV-2.

Study ID Serological test Description of test Thresholds for serological positivity
Agergaard 2020 IgG and IgM iFlash and DiaSorin iFlash SARS-CoV-2 N/S IgM/IgG cut-off: ≥12 AU/ml = positive.
DiaSorin SARS-CoV-2 S1/S2 IgG cut-off: ≥15 AU/ml = positive, 12
< x < 15 AU/ml = equivocal, and ≤12 AU/ml = negative.
Angulo-Bazán 2020 IgG and IgM Coretests ® COVID-19 IgM / IgG Ab Test (Core Technology Co. Ltd), a lateral flow immunochromatographic test that qualitatively
detects the presence of antibodies against SARS-CoV-2, with a sensitivity and specificity reported by the manufacturer for IgM / IgG of
97.6% and 100%, respectively
Not reported
Armann 2020 IgG Diasorin LIAISON® SARS-CoV-2 S1/S2 IgG Assay). All samples with a positive or equivocal LIAISON® test result, as well as all samples
from participants with a reported personal or household history of a SARS-CoV-2 infection, were re-tested with two additional
serological tests: These were a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitative detection of IgG
antibodies to the nucleocapsid protein of SARS-CoV-2 (Abbott Diagnostics® ARCHITECT SARS-CoV-2 IgG ) (an index (S/C) of < 1.4 was
considered negative whereas one >/= 1.4 was considered positive) and an ELISA detecting IgG against the S1 domain of the SARS-
CoV-2 spike protein (Euroimmun® Anti-SARS-CoV-2 ELISA) (a ratio < 0.8 was considered negative, 0.8–1.1 equivocal, > 1.1 positive)
Participants whose positive or equivocal LIAISON® test result could be confirmed by a positive test result in at least one additional
serological test were considered having antibodies against SARS-CoV_x0002_2.
Antibody levels > 15.0 AU/ml were considered positive and levels
between 12.0 and 15.0 AU/ml were considered equivocal.
Baettig 2020 IgG and IgM Used commercially available immunochromatography rapid test with SARS-CoV-2 protein-specific IgM and IgG. This test was
performed according to the manufacturers’ instructions with a reported sensitivity and specificity of 93% and 95%, respectively.
Not reported
Basso 2020 IgG and IgM Sera were collected approximately 3 weeks following exposure for the detection of antibodies against SARS-CoV-2. EDI Novel
Coronavirus COVID-19 lgG and IgM ELISA (Epitope Diagnostics, Inc., San Diego, CA, USA) were used for initial testing, and
supplemented with tests from DiaSorin (LIAISON SARS-CoV-2 S1/S2 IgG test), Abbott (Alinity i SARS-CoV-2 IgG), Roche (Elecsys Anti-
SARS-CoV-2) and Wantai (WANTAI SARS-CoV-2 Ab ELISA).
Not reported
Brown 2020 IgG and IgM ELISA (authors referenced another study) Reciprocal titers of >400 to be positive and reciprocal titers of
>100 but <400 to be indeterminate.
Chen 2020b IgG and IgM In-house enzyme immunoassay (EIA). 96-well plates were coated with 500 ng/mL of recombinant RBD or NP protein overnight,
incubating with diluted serum samples at 1:20. Plates were incubated with either anti-human IgM or IgG conjugated with HRP. Optical
density (OD) value (450nm-620nm) was measured.
Preliminary cut-off values were calculated as the mean of the
negative serum OD values plus 3 standard deviation (SD) from
90 archived healthy individuals in 2019. A close contact was
considered seropositive if OD of 1:20 diluted serum was above
the cut-off values for either IgM or IgG against both RBD and NP
protein
Chu 2020 IgG and IgM Serum samples were tested at CDC using a SARS-CoV-2 ELISA with a recombinant SARS-CoV-2 spike protein (courtesy of Dr. Barney
Graham, National Institutes of Health, Bethesda, MD, USA) as an antigen. Protein ELISA 96-well plates were coated with 0.15 μg/mL of
recombinant SARS-CoV-2 spike protein and ELISA was carried out as previously described. An optimal cutoff optical density value of
0.4 was determined for >99% specificity and 96% sensitivity. Serum samples from the case-patient were used as a positive control and
commercially available serum collected before January 2020 from an uninfected person as a negative control.
Total SARS-CoV-2 antibody titers >400 were considered
seropositive.
Dattner 2020 IgG Abbott SARS-CoV-2 IgG, whose specificity was estimated as ∼100% and whose sensitivity at ≥ 21 days was estimated as ∼85% Not reported
de Brito 2020 IgG and IgM Chemiluminescence 4 weeks after contact with the index case Not reported
Dimcheff 2020 IgG Serum IgG to thD4:D12e nucleoprotein of SARS-CoV-2 was measured using a Federal Food and Drug Administration (FDA)
emergency-use–authorized chemiluminescent microparticle immunoassay performed on an automated high throughput chemistry
immunoanalyzer (Architect i2000SR, Abbott Laboratories, Abbott Park, IL). The sensitivity of this assay is reported to be 100% with a
specificity of 99% at >14 days after symptom onset in those infected with SARS-CoV-2.1 At 5% prevalence, the positive predictive value is 93.4% and the negative predictive value
is 100%
Results are reported in a relative light units (RLU) index; a value
≥1.4 RLU is considered a positive antibody response.
Dub 2020 IgG IgG antibodies to SARS-CoV-2 nucleoprotein (The Native Antigen Company, United Kingdom) were measured
with a fluorescent bead-based immunoassay (manuscript in preparation). Antigen was conjugated on MagPlex
Microspheres and bound IgG antibodies were identified by a fluorescently labeled conjugated antibody (R_x0002_Phycoerythrin-
conjugated Goat Anti-Human IgG, Jackson Immuno Research, USA). The plate was read on
Luminex® MAGPIX® system. xPONENT software version 4.2 (Luminex®Corporation, Austin, TX) was used to
acquire and analyze data. Median fluorescent intensity was converted to U/ml by interpolation from a 5-
parameter logistic standard curve. The specificity and sensitivity of the assay was assessed using receiver operator curve (ROC) with
100% specificity and 97.9% sensitivity
MNT titre of ≥ 6 considered positive
FMIA titre 3·4 U/ml considered positive
Fontanet 2020 IgG Antibody responses to SARS-CoV-2 using several assays developed by Institut Pasteur : an ELISA N assay, detecting antibodies
binding to the N protein; a S-Flow assay, which is a flow-cytometry based assay detecting anti-S IgG; and a LIPS assay, which is an
immunoprecipitation-based assay detecting anti-N and anti-S1 IgG.
Participants were considered seropositive for SARS-CoV-2 if any
test was positive, since all tests had a specificity higher than 99%
with the cut-offs chosen for positivity
Fontanet 2020a Not specified Serological testing was conducted using the S-Flow assay, a flow_x0002_cytometry-based serological test developed by the Institut
Pasteur. The assay is based on the
recognition of the SARS-CoV-2 Spike protein expressed at the surface of 293T cells. In previous studies, the sensitivity of the assay was
estimated at 99.4% (95% CI = 96.6% - 100%) on a panel of 160 RT-PCR confirmed mild forms of COVID-1928, while its specificity was
found to be 100% (one-sided 97.5% CI = 97.4% - 100%) on a panel of 140 pre-epidemic sera
Not reported
Gu 2020 IgG Not described Not reported
Helsingen 2020 IgG Measurement of IgG antibodies was performed with a multiplex flow cytometric assay known as microsphere affinity proteomics
(MAP)
Not specified. Referenced
Hong 2020 IgG and IgM Qualitative colloidal gold assay (Innovita (Tangshan) Biological Technology, Co., Ltd, Tangshan, China), following manufacturers’
instructions. The sensitivity of the assay was 87.3% (95%CI 80.4–92.0%), and the specificity was 100% (95%CI 94.20–100%) according
to the instructions of the assay.
Not reported
Kuwelker 2020 IgG A two-step ELISA was used for detecting SARS-CoV-2-specific antibodies, initially by screening with receptor-binding domain (RBD)
and then confirming seropositivity by spike IgG. Endpoint titres were calculated as the reciprocal of the serum dilution giving an
optical density (OD) value=3 standard deviations above the mean of historical pre-pandemic serum samples. Individuals with no
antibodies were assigned a titre of 50 for calculation purposes. Neutralisation assays were used to quantify SARS-CoV-2-specific
functional antibodies. VN titres were determined as the reciprocal of the highest serum dilution giving no CPE. Negative titres (<20)
were assigned a value of 10 for calculation purpose.
Not specified.
Lewis 2020 Not specified ELISA (authors referenced another study) Not specified
Luo 2020a IgG and IgM Not described Asymptomatic: Specific IgM detected in serum.
Symptomatic: Detectable SARS-CoV-2–specific IgM and IgG in
serum, or at least a 4-fold increase in IgG between paired acute
and convalescent sera.
Macartney 2020 IgA, IgG, IgM SARS-CoV-2-specific IgG, IgA, and IgM detection was done using an indirect immunofluorescence assay (IFA) that has a sensitivity
compared with nucleic acid testing of detecting any of SARS-CoV-2-specific IgG, IgA, or IgM when samples were collected at least 14
days after illness onset of 91·3% (95% CI 84·9–95·6) and specificity of 98·9% (95% CI 98·4–99·3%; MVNO, personal communication).
Not specified
Martinez-Fierro 2020 IgG and IgM IgM and IgG against SARS-CoV-2 were determined using a total blood sample through a 2019 nCov IgG/IgM rapid test (Genrui
Biotech, Shenzen, China)
Not specified
Ng 2020 Not specified human ACE-2 (hACE2) protein (Genscript Biotech, New Jersey, United States) was coated at 100 ng/well in 100 mM carbonate-
bicarbonate coating buffer (pH 9.6). 3ng of horseradish peroxidase (HRP)-conjugated recombinant receptor binding domain (RBD)
from the spike protein of SARS-CoV-2 (GenScript Biotech) was pre-incubated with test serum at the final dilution of 1:20 for 1 hour
at 37°C, followed by hACE2 incubation for 1 h at room temperature.Serum samples were tested with a surrogate viral neutralising
assay for detection of neutralising antibodies to SARS-CoV-2.
A positive serological test result was concluded if the surrogate
viral neutralising assay for a particular sample resulted in
inhibition of 30% or greater (98·9% sensitivity and 100·0%
specificity)
Ogawa 2020 IgG Abbott® (Abbott ARCHITECT SARS-CoV-2 IgG test, Illinois, USA) Not specified
Poletti 2020 IgG Not described Not specified
Razvi 2020 IgG and IgM Blood samples were analysed on the day of collection using the Roche Elecsys Anti-Sars-CoV-2 serology assay. This
electrochemiluminescent immunoassay is designed to detect both IgM and IgG antibodies to SARS-CoV-2 in human serum and
plasma and has been shown to have a high sensitivity and specificity
Not specified
Schumacher 2020 IgG and IgM SARS-CoV-2-specific antibodies were measured in serum samples using an
electrochemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2, Roche Diagnostics, Rotkreuz, Switzerland).
Cut-off indices ≤1 reported as negative and indices >1 as positive.
Torres 2020 IgG and IgM Novel Coronavirus (2019-nCoV) IgG/IgM Test Kit (Colloidal gold) from Genrui Biotech Inc. The study nurse and/or technician viewed
the photo provided by the participant along with the participant’s self-report as to the visibility of the three bands, and determined
whether the tests were IgG+, IgM+, IgG & IgM+, Negative, Invalid, or Indeterminate. Participants were asked to attach a photo of the
test after 15 minutes had elapsed and self-report the appearance of the three lines, G (IgG), M (IgM), and C (test control)
Colour-coded - self-administered test: self-reporting the
appearance of the three lines, G (IgG), M (IgM), and C (test
control)
van der Hoek 2020 IgG Fluorescent bead-based multiplex-immunoassay. Referenced A cut-off concentration for seropositivity (2.37 AU/mL; with
specificity of 99% and sensitivity of 84.4%) was determined by
ROC-analysis of 400 pre-pandemic control samples
Wendt 2020 IgA and IgG ELISA (Euroimmun, Lübeck, Germany), following the manufacturer’s instructions. Inconclusive (≥0.8 and <1.1) or Positive (≥1.1
Yang 2020 IgA, IgG, IgM Serum immunoglobulin (Ig) antibody against the SARS-CoV-2 surface spike protein receptor-binding domain (RBD) was measured
using a chemiluminescence kit (IgM, IgG, and total antibody, Beijing Wantai Biotech, measured by cut-off index [COI]) or ELISA kit (IgA,
Beijing Hotgen Biotech, measured by optical density at 450/630 nm [OD450/630]). The cut-off for seropositivity was set according to
the manufacturer’s instruction, verified using positive (169 serum specimens from confirmed COVID-19 patients) and negative (128
serum specimens from healthy persons) controls, and both of sensitivity and specificity were 100%.
Virus neutralization assays were performed using SARS-CoV-2 virus strain 20SF014/vero-E6/3 (GISAID accession number
EPI_ISL_403934) in biosafety level 3 (BSL-3) laboratories. Neutralizing antibody (NAb) titer was the highest dilution with 50% inhibition
of cytopathic effect, and a NAb titer of ≥1:4 was considered positive.
Specimens with COI>1 (IgM, IgG, or total antibody),
OD450/630 > 0.3 (IgA) were considered positive.
Zhang 2020b IgG and IgM SARS-CoV-2-specific IgM and IgG were tested by paramagnetic particle chemiluminescent immunoassay using iFlash-SARS-CoV-2
IgM/IgG assay kit (Shenzhen YHLO Biotech Co., Ltd) and iFlash Immunoassay Analyzer (Shenzhen YHLO Biotech Co., Ltd). The specificity
and sensitivity of SARS-CoV-2 IgM and IgG detection were also evaluated
Not specified

Table 5. Quality of included studies.

Study Description of methods
and sufficient detail to
replicate
Sample
sources
clear
Analysis &
reporting
appropriate
Is bias
dealt
with
Applicability Notes
Abdulrahman 2020 Unclear Yes Yes No Yes
Adamik 2020 Unclear Unclear Yes No Unclear
Agergaard 2020 No Yes Yes No Yes
Angulo-Bazán 2020 Yes No Yes Unclear Yes
Armann 2020 Unclear Yes Yes No Yes
Arnedo-Pena 2020 Yes Yes Yes Unclear Yes
Baker 2020 Unclear Yes Yes Unclear Yes
Baettig 2020 Unclear Yes Yes Unclear Yes
Bao 2020 Unclear Yes Yes No Yes
Basso 2020 Unclear Yes Yes Unclear Yes
Bays 2020 Unclear Yes Yes No Yes
Bi 2020 Yes Yes Yes Unclear Yes
Blaisdell 2020 Yes No Yes Unclear Yes
Böhmer 2020 Yes Yes Yes Unclear Yes
Boscolo-Rizzo 2020 Unclear Yes Yes No Yes
Brown 2020 Yes Yes Yes Unclear Unclear
Burke 2020 Unclear No Yes No Yes
Canova 2020 Unclear Yes Yes Unclear Yes
Cariani 2020 Unclear Yes Unclear Unclear Yes
Charlotte 2020 Unclear Yes Yes Unclear Yes
Chaw 2020 Unclear Yes Yes Unclear Yes
Chen 2020 Unclear Unclear Yes No Unclear
Chen 2020a Unclear Yes Yes Unclear Yes
Chen 2020b Yes Yes Yes Unclear Yes
Chen 2020c Unclear No Yes No Yes
Cheng 2020 Yes No Yes Unclear Yes
Chu 2020 Yes Yes Yes Unclear Yes
Chu 2020a Unclear Unclear Unclear No Yes
Contejean 2020 Unclear Yes Yes Unclear Yes
COVID-19 National Emergency Response Center 2020 Unclear No Yes No Yes
Danis 2020 Yes Yes Yes No Yes
Dattner 2020 Yes Yes Yes Unclear Yes
de Brito 2020 Yes Yes Unclear Unclear Yes
Deng 2020 Unclear No Unclear Unclear Unclear
Desmet 2020 Yes Yes Yes No Unclear
Dimcheff 2020 Yes Unclear Yes Unclear Unclear
Dong 2020 Unclear No Unclear No Yes
Doung-ngern 2020 Yes Yes Yes Unclear Yes
Draper 2020 Yes Yes Yes No Yes
Dub 2020 Yes Yes Yes Unclear Yes
Expert Taskforce 2020 Unclear Unclear Yes Unclear Unclear
Fateh-Moghadam 2020 Unclear No Yes No Yes
Firestone 2020 Unclear Unclear Yes Unclear Yes
Fontanet 2020 Yes Yes Yes No Yes
Fontanet 2020a Yes Yes Yes No Yes
Gan 2020 Unclear Unclear Unclear Unclear Unclear
Ghinai 2020 Unclear Unclear Unclear Unclear Unclear
Gong 2020 Yes Yes Unclear Unclear Unclear
Gu 2020 Unclear Unclear Unclear No Unclear
Hamner 2020 Unclear Unclear Yes No Yes
Han 2020 Yes Yes Yes Unclear Yes
Heavey 2020 Unclear No Yes No Yes
Helsingen 2020 Yes Yes Yes Yes Yes
Hendrix 2020 Yes Yes Yes No Yes
Hirschman 2020 Unclear Unclear Unclear No Yes
Hobbs 2020 Yes Yes Yes Unclear Yes
Hoehl 2020 Yes Yes Yes Unclear Yes
Hong 2020 Yes Yes Yes Unclear Yes
Hu 2020 Unclear No Yes No Yes
Hua 2020 Yes Unclear Yes Unclear Yes
Huang 2020 Unclear Unclear Yes No Unclear
Huang 2020a Unclear Unclear Yes Unclear Unclear
Islam 2020 Yes No Yes No Yes
Jia 2020 Unclear Unclear Yes No Unclear
Jiang 2020 Yes Yes Unclear No Yes
Jing 2020 Yes Yes Yes Unclear Yes
Jing 2020a Unclear Yes Unclear Unclear Unclear
Jones 2020 Unclear Yes Yes Unclear Unclear
Kang 2020 Unclear Unclear Unclear Unclear Unclear
Kant 2020 Unclear Yes Unclear No Unclear
Kawasuji 2020 Unclear Yes Unclear Unclear Unclear
Khanh 2020 Yes Yes Yes No Yes
Kim 2020 Unclear Yes Yes Unclear Yes
Kim 2020a Unclear Yes Yes No Unclear
Kim 2020b Yes Yes Yes No Yes
Kumar 2020 Unclear Yes Unclear No Unclear
Kuwelker 2020 Unclear Yes Yes Unclear Yes
Kwok 2020 Unclear Unclear Yes Unclear Unclear
Ladhani 2020 No Unclear Unclear No Yes
Ladhani 2020a Unclear Unclear Yes Unclear Yes
Laws 2020 Unclear Unclear Yes Unclear Yes
Laxminarayan 2020 Yes No Yes No Yes
Lee 2020 Unclear Unclear Yes Unclear Unclear
Lee 2020a Unclear No Yes No Yes
Lewis 2020 Yes Yes Yes No Yes
Li 2020 Unclear Yes Unclear No Unclear
Li 2020a Unclear Unclear Unclear Unclear Unclear
Li 2020b Unclear Yes Unclear Unclear Unclear
Li 2020c Unclear No Unclear Unclear Unclear
Li 2020d Yes Yes Yes No Yes
Liu 2020 Unclear Unclear Unclear No Yes
Liu 2020a Yes Yes Yes Unclear Unclear
Liu 2020b Unclear Yes Yes Unclear Yes
Liu 2020c Unclear Unclear Unclear No Unclear
López 2020 Unclear Unclear Yes Unclear Yes
Lopez Bernal 2020 Yes Unclear Yes No Yes
Lucey 2020 Unclear Yes Yes No Yes
Luo 2020 Unclear Yes Yes Unclear Yes
Luo 2020a Unclear Yes Yes Yes Yes They use multiple
imputation to minimise
inferential bias, and
they discuss recall
bias, selection bias and
regression to the mean.
Lyngse 2020 Yes Unclear Yes Yes Yes They investigate bias
within their data and
discuss this fairly fully
Ma 2020 Unclear Unclear Unclear Unclear Unclear
Macartney 2020 Yes Unclear Yes Unclear Yes
Malheiro 2020 Yes Unclear Yes Unclear Yes
Maltezou 2020 Unclear Unclear Unclear Unclear Yes
Maltezou 2020a Unclear Unclear Unclear No Yes
Mao 2020 Unclear Unclear Yes No Unclear
Martinez-Fierro 2020 Unclear Yes Yes No Yes
Mponponsuo 2020 Unclear Yes Yes Yes Yes Recall bias was minimized
by examining multiple
data sources for both
index cases and exposed
persons
Ng 2020 Unclear Yes Yes Yes Yes Authors looked at
differences that could
have led to bias
Ning 2020 Unclear Unclear Unclear Unclear Unclear
Njuguna 2020 Unclear Unclear Yes Unclear Yes
Ogawa 2020 Unclear Unclear Yes No Yes
Paireau 2020 Unclear Yes Yes Unclear Yes
Park 2020 Unclear Yes Yes Unclear Yes
Park 2020a Unclear No Yes No Yes
Park 2020b Unclear Yes Yes No Unclear
Passarelli 2020 Unclear No Unclear Unclear Yes
Patel 2020 Yes Yes Yes Unclear Unclear
Pavli 2020 Unclear Yes Yes No Yes
Phiriyasart 2020 Yes Yes Yes No Yes
Poletti 2020 Unclear Yes Yes Yes Unclear
Pung 2020 Yes Unclear Yes Unclear Yes
Pung 2020a Unclear No Unclear Unclear Unclear
Qian 2020 Unclear Unclear Unclear No Unclear
Ravindran 2020 Unclear Unclear Unclear Unclear Unclear
Razvi 2020 Unclear Yes Yes No Yes
Rosenberg 2020 Yes Yes Yes No Yes
Roxby 2020 Yes Yes Yes Unclear Yes
Sang 2020 Unclear Yes Unclear No Unclear
Schumacher 2020 Unclear Yes Unclear Unclear Yes
Schwierzeck 2020 Unclear Yes Yes Unclear Yes
Shah 2020 Unclear No Unclear No Yes
Shen 2020 Yes Yes Yes Unclear Yes
Sikkema 2020 Unclear Yes Yes Unclear Yes
Son 2020 Unclear Unclear Yes No Yes
Song 2020 Unclear Yes Yes Unclear Yes
Speake 2020 Unclear Yes Yes Unclear Yes
Sugano 2020 Unclear Unclear Yes Unclear Yes
Stein-Zamir 2020 Yes Unclear Yes No Yes
Sun 2020 Unclear Unclear Unclear Unclear Unclear
Taylor 2020 Yes Yes Yes Unclear Yes
Teherani 2020 Unclear Yes Yes Unclear Yes
Thangaraj 2020 Unclear Yes Yes Unclear Unclear
Torres 2020 Yes Unclear Yes Unclear Yes
Tshokey 2020 Unclear Yes Yes Unclear Yes
van der Hoek 2020 Unclear Yes Yes No Yes
Wang 2020 Unclear Yes Unclear Unclear Yes
Wang 2020a Yes Unclear Yes Unclear Yes
Wang 2020b Yes Yes Yes No Yes
Wee 2020 Yes Yes Yes Unclear Yes
Wendt 2020 Yes Yes Yes Unclear Yes
Wolf 2020 Yes Yes Yes Unclear Yes
Wong 2020 Yes Yes Yes Unclear Yes
Wood 2020 Unclear No Yes Unclear Yes
Wu 2020 Yes Unclear Yes Unclear Yes
Wu 2020a Yes Unclear Yes Unclear Yes
Xie 2020 Unclear Yes Yes Unclear Yes
Xin 2020 Yes No Yes No Yes
Yang 2020 Unclear Yes Unclear Unclear Yes
Yau 2020 Unclear Yes Unclear Unclear Unclear
Ye 2020 Unclear Unclear Unclear Unclear Unclear
Yoon 2020 Yes Yes Yes Unclear Yes
Yousaf 2020 Unclear Yes Unclear Unclear Unclear
Yu 2020 Yes No Yes No Yes
Yung 2020 Unclear Yes Yes No Yes
Zhang 2020 Unclear Unclear Unclear No Unclear
Zhang 2020a Yes Unclear Yes Unclear Unclear
Zhang 2020b Unclear Yes Unclear Unclear Yes
Zhang 2020c Unclear Unclear Unclear Unclear Unclear
Zhang 2020d Unclear Yes Unclear Unclear Unclear
Zhuang 2020 Unclear No Yes No Unclear

Three studies (Ladhani 2020a, Speake 2020, Yang 2020) performed viral culture, while 10 studies (Böhmer 2020, Firestone 2020, Jiang 2020, Ladhani 2020a, Lucey 2020, Pung 2020, Sikkema 2020, Speake 2020, Taylor 2020, Wang 2020) performed genome sequencing (GS) plus phylogenetic analysis.

Frequency of SARS-CoV-2 attack rates (ARs)

Twenty-three studies reported data on attack rates using RT-PCR ( Table 6). The settings included healthcare (n=3), household (n=8), public transport (n=2), educational settings (n=3). In one study of 84 children in daycare centres during the first few weeks of the pandemic (Desmet 2020), the AR was 0%; similar results were reported in another study of hospital healthcare workers (Basso 2020). The frequency of ARs in the remaining 21 studies ranged from 3.5 to 75% ( Figure 3a). The ARs were highest in weddings (69%), prison (69.5%) and households (75%). Attack rates appeared lower in healthcare settings; two healthcare settings with higher ARs (Ladhani 2020, Ladhani 2020a) included nursing home residents – the definition of SARS-CoV-2 infection in both studies did not include the full constellation of respiratory and non-respiratory symptoms. In sports settings, the AR during matches was between 4.2% and 4.7%.

Figure 3a. Primary attack rates of SARS-CoV-2 in close contacts (PCR).

Figure 3a.

Table 6. Main results of included studies.

Study ID Type of transmission Total number of contacts Cycle threshold Attack rates and/or secondary attack rates (SAR) Notes
Abdulrahman 2020 Community Eid Alfitr
Pre-: 71,553; Post-: 76,384
Ashura
Pre-: 97,560; Post-: 118,548
Not reported Eid Alfitr
Pre-: 2990 (4.2%); Post-: 4987 (6.7%); p <0.001
Ashura
Pre-: 3571 (3.7%); Post-: 7803 (6.6%); p <0.001
The rates of positive tests was significantly
greater after religious events
Adamik 2020 Household Unclear Not reported Unclear: 3553 (AR 26.7%)
Agergaard 2020 Household PCR: 5
Serology: 5
Not reported Index case plus 1 family member tested positive-
PCR
All 5 displayed a serological SARS-CoV-2 N/S IgG
response
Angulo-Bazán 2020 Household 52 households (n=236 people)
4.5±2.5 members per household
Not reported Serology: Amongst cohabitants, SAR was 53.0%
(125 cases): 77.6% of cases were symptomatic
Convenience sampling, no component of
temporality, selection bias
Armann 2020 Local
Household
2045 in Phase 1
1779 in Phase 2
N/A Serology: 12/2045 (0.6%)
Serology: 12/1779 (0.7%)
Arnedo-Pena 2020 Household 745 Not reported 11.1% (95% CI 9.0–13.6)
Baker 2020 Nosocomial 44 Not reported 3/44 (6.8%): 1 of these was also exposed to a
household member with COVID-19.
Recall error and bias, report is limited to
a single exposure, change in mask policy
partway through the exposure period
Baettig 2020 Local 55 Not reported Serologic attack rates: 2/55 (3.6%) Serological testing was positive for the 2
contacts 14 days after index case
Bao 2020 Community 57 index cases
1895 exposed
Not reported SAR was 3.3% at the bathing pool, 20.5% in
the colleagues’ cluster and 11.8% in the family
cluster.
Delayed detection of the activity trajectory of
the primary case, reporting bias, overlap of
close contacts
Basso 2020 Nosocomial 60 HCWs - ≥106 unique high-risk
contacts
Not reported Attack rate: 0/60 (0%)
Serology: 0/60 (0%)
Delay in diagnosing index case, recall bias
Bays 2020 Nosocomial 421 HCWs Not reported 8/421 (1.9%) In all 8 cases, the staff had close contact with
the index patients without sufficient PPE.
Hospital staff developing ILI symptoms were
tested for SARS-CoV-2, regardless of whether
they had contact with an index patient
Bi 2020 Local
Household
Community
1,296 Not reported 98/1286 (7.6%)
Blaisdell 2020 Community 1,022 Not reported 1.8% of camp attendees (10 staff members and
8 campers)
Travel was assumed to be from home state
but intermediate travel might have occurred
Böhmer 2020 Local
Household
241 Not reported 75·0% (95% CI 19·0–99·0; three of four people)
among members of a household cluster in
common isolation, 10·0% (1·2–32·0; two of 20)
among household contacts only together until
isolation of the patient, and 5·1% (2·6–8·9; 11 of
217) among non-household, high-risk contacts.
Boscolo-Rizzo 2020 Household 296 Not reported 74/296 (25.0%, 95% CI 20.2–30.3%) The prevalence of altered sense of smell or
taste was by far lower in subjects negative to
SARS-CoV-2 compared to both positives (p
< 0.001) and non-tested cases (p < 0.001).
Brown 2020 Local 21 Not reported Serologic attack rate: 2/21 (1%) Social desirability bias likely
Burke 2020 Household 445 Not reported 0.45% (95% CI = 0.12%–1.6%) among all close
contacts, and a symptomatic secondary attack
rate of 10.5% (95% CI = 2.9%–31.4%) among
household members.
2 persons who were household members
of patients with confirmed COVID-19 tested
positive for SARS-CoV-2.
Canova 2020 Nosocomial 21 Not reported 0/21 (0%)
Cariani 2020 Nosocomial Unclear 33.6 to 38.03 182 out of 1683 (10.8%) tested positive; 27 of
whom had close contact with COVID-positive
patients
Unclear how many HCWs had close contact;
likelihood of recall bias
Charlotte 2020 Community 27 Not reported 19 of 27 (70%) tested positive High risk of selection bias: The index case-
patients were not identified. A majority of
patients were not tested for SARS-CoV-2
Chaw 2020 Local
Community
1755 Not reported Close contact: 52/1755 (29.6%)
Nonprimary attack rate: 2.9% (95% CI 2.2%–
3.8%)
Potential environmental factors were not
accounted for: relative household size, time
spent at home with others, air ventilation, and
transmission from fomites.
Chen 2020 Aircraft 335 Not reported 16/335 (4.8%) Recall bias. Did not perform virus isolation
and genome sequencing of the virus, which
could have provided evidence of whether viral
transmission occurred during the flight.
Chen 2020a Local
Household
209 Not reported 0/209 (0%)
Chen 2020b Nosocomial 105 Not reported Serology: 18/105 (17.1%)
Chen 2020c Local
Community
Household
Nosocomial
2147 Not reported 110/2147 (5.12%)
Cheng 2020 Household
Nosocomial
2761 Not reported 0.70%
Chu 2020 Community 50 exposed Not reported None for antigen or antibody: 0/50 (0%) Testing was biased toward contacts who knew
the case-patient personally (office co-workers)
or provided direct care for the case-patient
(HCP).
Chu 2020a Household 526 exposed Not reported 48 (9%) (CI 7-12%) Very high risk of selection bias
Contejean 2020 Nosocomial 1344 exposed Not reported 373 (28%)
COVID-19 National Emergency Response Center 2020 Local
Household
Nosocomial
2370 Not reported 13/2370 (0.6%) There were 13 individuals who contracted
COVID-19 resulting in a secondary attack rate
of 0.55% (95% CI 0.31–0.96). There were 119
household contacts, of which 9 individuals
developed COVID-19 resulting in a secondary
attack rate of 7.56% (95% CI 3.7–14.26).
Danis 2020 Local
Household
Chalet: 16
School: 172
Not reported Attack rate: 75% in chalet
Attack rate: 0% in school
Only 73 of 172 school contacts were tested
- all tested negative
Dattner 2020 Household 3353 Not reported Attack rates: 25% in children and 44% adults (45% overall)
Serology: 9/714 (1.3%)
de Brito 2020 Household 24 exposed Not reported RT-PCR: 6/7 (86%); Seropositivity: 18/24 (75%)
Deng 2020 347 Not reported 25/347 (7.2%)
Desmet 2020 Local 84 38.8 Attack rate: 0/84 (0%) Ct reported for only one test result
Dimcheff 2020 Community
Nosocomial
Household
1476 Not reported Seroprevalence 72/1476: 4.9% (95% CI,
3.8%–6.1%)
Dong 2020 Household 259 Not reported 53/259 (20.5%)
Doung-ngern 2020 Local 211 cases plus
839 non-matched controls
Not reported
Draper 2020 Local
Household
Nosocomial
445 Not reported 4/445 (0.9%) None of the 326 aircraft passengers or
4 healthcare workers who were being
monitored close contacts became cases.
Dub 2020 Local
Household
121 Not reported Child index case: No positive cases
Adult index case: 8/51 (16%)
Serology: 6/101 (5.9%)
Expert Taskforce 2020 Local Unclear Not reported Attack rate 20.4% Attack rates were highest in 4-person cabins
(30.0%; n = 18), followed by 3-person cabins
(22.0%; n = 27), 2-person cabins (20.6%; n =
491), and 1-person cabins (8%; n = 6).
Fateh-Moghadam 2020 Community 6690 Not reported 890/6690 (13.3%)
Firestone 2020 Local Unclear Not reported 41 (80%) interviewed patients with primary
event-associated COVID-19 reported having
close contact with others during their infectious
period, with an average of 2.5 close contacts per
patient.
36 (75%) of 48 interviewed patients with primary
event-associated cases reported having close
contact with persons in their household while
infectious, and 17 (35%) reported having
other (social/workplace) close contacts while
infectious.
Fontanet 2020 Local 661 N/A Serology: 171/661 (25.9%, 95%CI 22.6-29.4)
Fontanet 2020a Local 510 N/A Serology: 45/510 (8.8%)
Gan 2020 Local
Household
Community
Unclear Not reported Not reported Family clusters accounted for 86.9% (914/1
050) of cases, followed by party dinners (1.1%)
Ghinai 2020 Community Unclear Not reported Unclear
Gong 2020 Household
Community
Unclear Not reported Unclear
Gu 2020 Local 14 Not reported RT-PCR - 3/14 (21.4%)
Serology - 2/14 (14.3%)
Hamner 2020 Local 60 Not reported Confirmed: 32/60 (53.3%)
Probable: 20/60 (33.3%)
Han 2020 Community 192 Not reported 7/192 (3.7%)
Heavey 2020 Local 1155 Not reported 0/1155 (0%)
Helsingen 2020 Local Training arm: 1,896
Nontraining arm: 1,868
Not reported 11/1896 (0.8%) vs 27/1868 (2.4%); P=0.001
Hendrix 2020 Local 139 exposed Not reported 0% Six close contacts of stylists A and B outside
of salon A were identified: four of stylist
A and two of stylist B. All four of stylist A’s
contacts later developed symptoms and had
positive PCR test results for SARS-CoV-2.
These contacts were stylist A’s cohabitating
husband and her daughter, son-in-law, and
their roommate, all of whom lived together
in another household. None of stylist B’s
contacts became symptomatic.
Hirschman 2020 Household
Community
58 Not reported 27/58 (47%)
Hobbs 2020 Local
Household
Community
397 Not reported Not reported
Hoehl 2020 Local
Community
825 children and 372 staff: 7,366 buccal
mucosa swabs and 5,907 anal swabs
Not reported 0% viral shedding in children; 2/372 (0.5%)
shedding for staff. No inapparent transmissions
were observed
Study was conducted in the summer of 2020,
when activity of other respiratory pathogens
was also low
Hong 2020 Household 431 tests Not reported 0/13 (0%) Index cases had lived with their family
members without personal protections for a
total of 258 person-days.
Hu 2020 Household
Community
15648 Not reported 471/15648 (3%)
Hua 2020 Household 835 Not reported 151/835 (18.1%)
Huang 2020 Household
Community
22 Not reported 7/22 (31.8%)
Huang 2020a Local
Household
Community
Nosocomial
3795 Not reported 32/3795 (0.84%)
Islam 2020 Household
Local
Community
Nosocomial
391 Not reported The overall secondary clinical attack rate was
4.08 (95% CI 1.95–6.20)
Jia 2020 Household Unclear Not reported Attack rate 44/583 (7.6%)
Jiang 2020 Household
Community
300 Not reported 6/300 (2%)
Jing 2020 Household Unclear Not reported Household contacts 13·2%
Non-household contacts 2·4%
The risk of household infection was
significantly higher in the older age group
(≥60 years)
Jing 2020a Household
Community
Unclear Not reported Close contacts 17.1% to 19%
Family members 46.1% to 49.6%
Jones 2020 Local 128 Not reported 6/128 (4.7%)
Kang 2020 Local 5517 Not reported 96/5517 (1.7%)
Kant 2020 Local
Community
Nosocomial
Not reported Not reported Not reported No details on number of contacts for index case
Kawasuji 2020 Nosocomial 105 Not reported 14/105 (1.33%)
Khanh 2020 Community 217 Not reported 16/217 (7.4%)
Kim 2020 Household 207 17.7 to 30 1/207 (0.5%)
Kim 2020a Household
Community
4 18.7 to 32.1 N/A
Kim 2020b Nosocomial 3,091 respiratory samples from 2,924
individuals
Not reported 3/290 (1%)
Kumar 2020 Community 822 Not reported 144/822 17.5%) Spread of infection within the state was
significantly higher from symptomatic cases,
p=0.02
Kuwelker 2020 Household 179 N/A 45% The elderly (>60 years old) had a significantly
higher attack rate (72%) than adults< 60years
old (46%, p=0·045)
Kwok 2020 Local
Household
206 Not reported 24/206 (11.7%)
Ladhani 2020 Nosocomial 254 Not reported Unclear: 53/254 (21%) tested positive. Staff working across different care homes
(14/27, 52%) had a 3.0-fold (95% CI, 1.9–4.8;
P<0.001) higher risk of SARS-CoV-2 positivity
than staff working in single care homes
(39/227, 17%).
Ladhani 2020a Nosocomial Residents: 264
Staff members: 254
Not specified Unclear: 105/264 (53%) residents tested positive Infectious virus recovery in asymptomatic
staff and residents emphasises their
likely importance as silent reservoirs and
transmitters of infection and explains the
failure of infection control measures which
have been largely based on identification of
symptomatic individuals.
Laws 2020 Household 188 Not reported 55/188 (29.3%)
Laxminarayan 2020 Local
Household
Community
575,071 Not reported 10.7% (10.5 to 10.9%) for high-risk contacts
4.7% (4.6 to 4.8%) for low-risk contacts
79.3% (52.9 to 97.0%) for high-risk travel exposure
Lee 2020 Household 12 Not reported 0/12 (0%)
Lee 2020a Household 23 Not reported 1/23 (4.4%)
Lewis 2020 Household 188 Not reported RT-PCR: 55/188 (29%)
Serology: 8/52 (15%)
Li 2020 Household 5 19.66 to 26.16 4/5 (80%)
Li 2020a Household
Nosocomial
7 Not reported 7/7 (100%) During January 14–22, the authors report that
index patient had close contact with 7 persons
Li 2020b Household 14 Not reported 14/14 (100%)
Li 2020c Household Unclear Not reported Unclear In COFs, the transmission rates of respiratory
droplets in secondary and non-infected
patients were 11.9 % and 66.7 %, respectively,
while the transmission rates of respiratory
droplets with close contacts were 88.1 % and
33.3 %, respectively. In SOFs, the proportion
of respiratory droplet and respiratory droplet
transmission with close contacts was 40 % and
60 %, respectively
Li 2020d Household 392 Not reported 64/392 (16.3%)
Liu 2020 Household 7 Not reported 4/7 (57.1%)
Liu 2020a Nosocomial 30 Not reported N/A
Liu 2020b Household
Community
Nosocomial
11580 Not reported 515/11580 (4.4%)
Liu 2020c Unclear 1150 Not reported 47/1150 (4.1%) The 16 confirmed cases who had previously
been asymptomatic accounted for 236 close
contacts, with a second attack rate of 9.7%,
while the remaining 131 asymptomatic
carriers accounted for 914 close contacts, with
a second attack rate of 2.6% (p<0.001)
López 2020 Local
Household
285 Not reported Facility SAR: 22/101 (21.8%)
Overall SAR: 38/184 (20.7%)
Variation in hygiene procedures across 3
facilities. Facility A required daily temperature
and symptom screening for the 12 staff
members and children and more frequent
cleaning and disinfection; staff members
were required to wear masks. Facility B:
temperatures of the five staff members
and children were checked daily, and more
frequent cleaning was conducted; only staff
members were required to wear masks.
Facility C: 84 staff members and children
check their temperature and monitor their
symptoms daily; masks were not required for
staff members or children.
Lopez Bernal 2020 Household
Community
472 Not reported 37% (95% CI 31–43%)
Lucey 2020 Nosocomial Not specified N/A Not reported
Luo 2020 Community 243 Not reported 12/243 (4.9%) No viral genetic sequence data were available
from these cases to prove linkage; and some
of the secondary and tertiary cases could
have been exposed to unknown infections,
especially asymptomatic ones, before or after
the bus trips.
Luo 2020a Household
Community
Nosocomial
3410 Not reported 127/3410 (3.7%)
Lyngse 2020 Household 2226 Not reported 371/2226 (16.7%)
Ma 2020 Unclear 1665 Not reported 10/1/1665 (0.6%) Only close contacts who fell ill were tested
(n=10)
Macartney 2020 Local 633 Not reported 18/633 (1.2%)
Serologic attack rates: 8/171 (4.8%)
Malheiro 2020 Household 1627 Not reported Overall AR 154/1627 (9.5%)
Maltezou 2020 Household Unclear <25 (28.1%)
25–30 (26.8%)
>30 (45.1%)
Median attack rate 40% (range: 11.1%–100%)
per family.
Maltezou 2020a Household Unclear Not reported Median attack rate: 60% (range: 33.4%-100%) Adults were more likely to develop a severe
clinical course compared to children (8.8%
versus 0%, p-value=0.021)
Mao 2020 Household
Local
Unclear Not reported 6.10% Average attack rate was 8.54% (1.02–100%)
Martinez-Fierro 2020 Unclear 81 Not reported 34/81 (42%)
Serologic attack rates: 13/87 (14.9%)
16% of contact showed positive serology after
>2 weeks
Mponponsuo 2020 Nosocomial 38 N/A 0/38 (0%)
Ng 2020 Household
Local
Community
13026 Not reported 188/7770 (2.4%)
Household: 5·9%
Work contacts: 1.3%
Social contacts: 1.3%
Serology: 44/1150 (3.8%)
Serology results were positive for 29 (5·5%)
of 524 household contacts, six (2·9%) of 207
work contacts, and nine (2·1%) of 419 social
contacts.
Ning 2020 Household
Local
Community
Unclear Not reported Imported cases: 69/3435 (0.8%)
Local cases: 31/3666 (2.0%)
Njuguna 2020 Local 98 Not reported Attack rate 57% to 82%
Ogawa 2020 Nosocomial 30 PCR/serology 33.53 to 36.83 0/15 (0%) for both PCR and serology
Paireau 2020 Household
Local
Nosocomial
6028 Not reported 248/6028 (4.1%) Family contacts, index case was 60–74, or
older than 75 years old were significantly
associated with increased odds of
transmission. The proportion of nosocomial
transmission was significantly higher than in
contact tracing (14% vs 3%, p<0.001)
Park 2020 Local
Household
Community
328 17.7 to 35 22/328 (6.7%)
Park 2020a Household
Non-household
59,073 Not reported Household contacts: 11.8% (95% CI 11.2%–
12.4%)
Non-household contacts: 1.9% (95% CI
1.8%–2.0%)
Park 2020b Local
Household
441 Not reported Attack rate 43.5% (95% CI 36.9%–50.4%)
Secondary attack rate 16.2% (95% CI 11.6%–
22.0%)
Passarelli 2020 Nosocomial 6 Not reported 2/6 (33.3%)
Patel 2020 Household 185 Not reported 79/185 (43%) Contacts not reported as tested
Pavli 2020 Aircraft 891 Not reported 5/891 (0.6%)
Phiriyasart 2020 Household 471 Not reported 27/471 (5.7%)
Poletti 2020 Unclear 2484 Not reported 2824/5484 (51.5%)
Pung 2020 Local
Community
425 Not reported 36/425 (8.5%)
Pung 2020a Household Unclear Not reported 43/875 (4.9%)
Qian 2020 Local
Household
Community
Not reported Not reported Not reported Home‐based outbreaks were the dominant
category (254 of 318 outbreaks; 79.9%),
followed by transport‐based outbreaks (108;
34.0%)
Ravindran 2020 Local Not reported Not reported Attack rate 61% to 77% All attendees participated in activities resulting
in potential exposure, such as shaking hands,
kissing, dancing, sharing
drinks and sharing shisha (smoking water pipes).
Razvi 2020 Nosocomial 2521 Not reported Serologic attack rate 19.4%
Rosenberg 2020 Household 498 Not reported 286/498 (57%)
Roxby 2020 Nosocomial 142 Not reported Attack rate in 1st round: 5/142 (3.5%) One additional positive test result was
reported for an asymptomatic resident who
had negative test results on the first round.
Sang 2020 Household 6 Not reported 4/6 (66.7%)
Schumacher 2020 Local Quarantine phase: 757 tests
Match phase: 1167 tests
Unclear Quarantine phase AR: 3.6%
Match phase AR: 4.2%
Serology: 1.1%
Schwierzeck 2020 Nosocomial 48 16.03 to 32.98 9/48 (18.8%) Ct values of symptomatic cases were
significantly lower compared to asymptomatic
cases 22.55 vs 29.94, p<0.007 (approximately
200-fold higher viral load)
Shah 2020 Household 386 Not reported 34/386 (8.8%)
Shen 2020 Household
Community
480 Not reported Close contact: 2/7 (29%)
Casual contact: 3/473 (0.6%)
Sikkema 2020 Nosocomial 1796 Not specified. WGS for Ct <32 Attack rate 96/1796 (5%) 46 (92%) of 50 sequences from health-care
workers in the study were grouped in three
clusters. Ten (100%) of 10 sequences from
patients in the study grouped into the same
three clusters:
Son 2020 Household 3223 Not reported 8.2% (95% CI, 4.7 to 12.9)
Song 2020 Household 20 Not reported 16/20 (80%)
Speake 2020 Aircraft 111 Not reported 11/111 (9.9%)
Stein-Zamir 2020 Local 1312 Not reported Attack rate 178/1312 (13.6%)
Sugano 2020 Local 72 Not reported 23/72 (31.9%)
Sun 2020 Household Unclear Not reported 34.43%
Taylor 2020 Nosocomial 600 Not reported Resident attack rate: 137/259 (52.9%) 1st round
HCW Attack rate: 114/341 (33.4%)
Teherani 2020 Household 144 Not reported 67/144 (46.5%) Of the total number of household contacts, at
least 29 (20%) had known SARS-CoV2 testing.
Child-to-adult transmission was suspected in
7/67 cases (10.5%).
Thangaraj 2020 Community 26 Not reported 17/26 (65.4%)
Torres 2020 Community 1244 N/A Overall serologic attack rate: 139/1244 (11.2%)
Tshokey 2020 Local
Community
1618 Not reported 14/1618 (0.9%) SAR: High-risk contacts was 9.0% (7/75),
and that among the primary contacts was
0.6% (7/1,095), and none (0/448) among the
secondary contacts.
van der Hoek 2020 Household 174 25.1 to 35.1 47/174 (27%)
Serology on day 3 - family members: 43/148
(29.1%)
Wang 2020 Nosocomial
Household
43 Not reported 10/43 (23.3%)
Wang 2020a Household 155 Not reported 47/155 (30%)
Wang 2020b Household 335 Not reported 77/335 (23%)
Wee 2020 Nosocomial 298 Not reported 1/298 (0.3%)
Wendt 2020 Nosocomial 254 Not reported 0/254 (0%)
Serologic attack rates 0/23 (0%)
Wolf 2020 Household 4 Not reported 3/4 (75%) 7-month old female who was breastfed, was
asymptomatic throughout the observation
period and never developed fevers or any
other symptoms, despite continuous exposure
to her parents and siblings. She remained
SARS-CoV-2 PCR-negative in repeat testing of
pharyngeal swab and stool specimens over
the entire observation period.
Wong 2020 Nosocomial 76 tests were performed on 52
contacts
Not reported 0/52 (0%) Findings suggest that SARS-CoV-2 is not
spread by an airborne route. Ct value for
throat and tracheal aspirate of index case
were 22.8 and 26.1 respectively
Wood 2020 Household Not reporred Not reported Not reported
Wu 2020 Household
Local
Community
2994 Not reported 71/2994 (2.4%)
Wu 2020a Household 148 Not reported 48/148 (32.4%)
Xie 2020 Household 56 Not reported 0/56 (0%)
Xin 2020 Household 187 Not reported 19/187 (17.9%)
Yang 2020 Household
Local
1296 Not reported 0/1296 (0%)
Serologic attack rates: 0/20 (0%)
Viral culture of 4 specimens with Ct <30 were
negative
Yau 2020 Nosocomial 330 Not reported 22/330 (6.7%)
Ye 2020 Local
Community
1293 Not reported 39/1,293 (3.02%)
Yoon 2020 Local 190 N/A 0/190 (0%)
Yousaf 2020 Household 198 Not reported 47/198 (23.7%)
Yu 2020 Household 1587 Not reported 150/1587 (9.5%)
Yung 2020 Household 213 Not reported Attack rate 6.1%
Zhang 2020 Aircraft 4492 Not reported Attack rate 161/4492 (3.6%) The authors report attack rate of 0.14% based
on 94 flights (n=14 505); however, only 4492
people were screened
Zhang 2020a Household
Local
Community
369 Not reported 12/369 (3.3%, 95% CI 1.9%–5.6%)
Zhang 2020b Household 10 Not reported 0/10 (0%)
Serologic attack rates: 0/10 (0%)
Zhang 2020c Local
Household
93 Not reported 5/93 (5.4%)
Zhang 2020d Local 8437 Not reported 25/8437 (0.3%)
Zhuang 2020 Household
Community
8363 Not reported 239/8363 (2.9%)

Twenty-nine studies reported data on ARs using serology ( Table 6). The settings included educational (n=4), households (n=4) and healthcare (n=3). In eight studies, the frequency of attack was 0%. The frequency of attacks in the remaining 21 studies ranged from 0.7% to 75% ( Figure 3b). The frequency of attacks was highest in households but lower in educational settings - especially daycare centres.

Figure 3b. Primary attack rates of SARS-CoV-2 in close contacts (serology).

Figure 3b.

Frequency of SARS-CoV-2 secondary ARs

Overall, 126 studies (73.7%) reported data on secondary ARs ( Table 6). The studies reported the rates based on RT-PCR tests, except for one study (Angulo-Bazán 2020) that used serology. In 16 of these studies, the SAR was 0%. The secondary ARs in the remaining 110 studies ranged from 0.3 to 100% (see Figure 4). The highest frequencies of secondary ARs (75–100%) occurred in household or quarantine settings; similar findings were observed when studies with higher reporting quality were examined (57–75%). In the three studies of index or primary cases with recurrent infections, there was no positive case amongst the 1518 close contacts across the studies.

Figure 4. Frequency of secondary attack rates of SARS-CoV-2 with Close Contacts.

Figure 4.

Risk of infection

Forty-six studies (26.9%) reported results on the risk of infection ( Table 7). One study of airline passengers (Khanh 2020) showed that seating proximity was significantly associated with the risk of contracting SARS-CoV-2 (RR 7.3, 95% CI 1.2–46.2); a second study (Speake 2020) reported that not sitting by the window was associated with a significantly increased risk of infection (RR 5.2; 95% CI 1.6–16.4; p<0.007)). The results of five studies (Chen 2020b, Doung-ngern 2020, Hobbs 2020, Wang 2020b, Wu 2020) showed that use of face covering during close contact with infected cases was associated with significantly lower risks of infection compared with no face covering; findings from one of these studies (Doung-ngern 2020) showed that wearing masks all the time during contact was not significantly different from wearing masks sometimes. The result of one study (Rosenberg 2020) showed that the incidence of infection significantly increased with age (p<0.0001), while those from another study (Poletti 2020) showed that being 70 years or older was associated with a significantly increased risk of SARS-CoV-2-related death (p<0.001), while another study (Zhang 2020a) reported that elderly close contacts (≥60 years) had a higher SAR compared with younger age groups. Findings from five studies (Bi 2020, Hu 2020a, Islam 2020, Luo 2020a, Wu 2020, Zhang 2020a) showed that household contact settings had significantly higher risks of infection compared with other types of contact settings, e.g., social, healthcare, workplace and public transport. One study (Lewis 2020) showed that the risk of infection was significantly increased amongst household contacts who were immunocompromised (OR 15.9, 95% CI 2.4–106.9). Finally, three studies (Bi 2020a, Wu 2020, Zhang 2020a) showed that the more frequent contacts with an index case was significantly associated with an increased risk of infection.

Table 7. Risk of infection in close contacts.

Study ID Type of
transmission
Risk of infection
Abdulrahman 2020 Community Eid Alfitr: Pre-: 2990 (4.2%); Post-: 4987 (6.7%); p <0.001; Ashura: Pre-: 3571 (3.7%); Post-: 7803 (6.6%); p <0.001
Arnedo-Pena 2020 Household The health profession of index case was a significant protective factor (p<0.007). Older age of secondary cases, two household members, and
higher age of index case were significantly associated with elevated risk of infection: p<0.001 in each case
Bi 2020 Local
Household
Community
Household contact (OR 6·3; 95% CI 1·5–26·3) and travelling together (OR 7·1; 1·4–34·9) were significantly associated with infection. Reporting
contact that occurred often was also associated with increased risk of infection compared with moderate-frequency contact (OR 8·8; 95% CI
2·6–30·1)
Chen 2020b Nosocomial In multivariate analysis, there existed higher risk of seroconversion for close contacts with patient 2 (OR, 6.605, 95% CI, 1.123, 38.830) and
doctors exposed to their patient (OR, 346.837, 95% CI 8.924, 13479.434), while the lower risk of seroconversion was closely related to direct
contact with COVID-19 patients wearing face mask (OR, 0.127, 95% CI 0.017, 0.968).
Chen 2020c Local
Community
Household
Nosocomial
Infection rate is highest when living with the case (13.26%), followed by taking the same means of transportation (11.91%). After removing
the influence factors of the "super spreader" incident, the infection rate of vehicle contact dropped to 1.80%. The infection rate (7.18%)
of entertainment activities such as gatherings, meeting guests, and playing cards was also relatively high, as was short-term face-to-face
unprotected conversations or doing errands (6.02%).
There was a statistically significant difference in the infection rate among the four categories of life contact, transportation contact, medical
contact, and other contact (p<0.005).
participation in Buddhist gatherings caused transmission. A total of 28 people were diagnosed as confirmed cases of new coronavirus
pneumonia, 4 were asymptomatic infections, and the infection rate of close contacts reached 32.99% (32/97), which was much higher than the
average infection rate (6.15). %), the difference is statistically significant (p<0.005).
Cheng 2020 Household
Nosocomial
The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure
to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases
from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI,
0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family
contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%])
and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]).
Chu 2020a Household Five (10%) of 48 secondary cases compared with 130 (33%) of 398 non-case household contacts reported potential community exposures:
unadjusted OR 0.24 (95%CI 0.09 to 0.62), p=0.003
Dattner 2020 Household PCR: 44% of adults were infected compared to 25% of the children (n=3353: 1809 children and 1544 adults)
Serology: 34% of these children and 48% of the adults tested serologically positive (n=705: 417 children and 288 adults
Dimcheff 2020 Community
Nosocomial
Household
HCWs exposed to a known COVID-19 case outside work had a significantly higher seroprevalence at 14.8% (23 of 155) compared to those who
did not 3.7% (48 of 1,296; OR, 4.53; 95% CI, 2.67–7.68; P < 0.0001)
Doung-ngern 2020 Local Wearing masks all the time during contact was independently associated with lower risk of COVID-19 infection compared to not wearing
masks (aOR 0.23, 95% CI 0.09–45 0.60), while wearing masks sometimes during contact was not (aOR 0.87, 95% CI 0.41–1.84).
Maintaining at least 1m distance from a COVID patient (aOR 0.15, 95% CI 0.04–0.63) and duration of close contact ≤15 minutes versus longer
(aOR 0.24, 95% CI 0.07–0.90) were significantly associated with lower risk of infection transmission
Fateh-Moghadam 2020 Community Workplace exposure was associated with higher risk of becoming a case than cohabi_x0019_ng with a case or having a non-cohabiting family
member or friend who was a case.
The greatest risk of transmission to contacts was found for the 14 cases <15 years of age (22.4%); 8 of the 14, who ranged in age from <1
to 11 years) infected 11 of 49 contacts.
Fontanet 2020a Local No significant difference in attack rates across primary school pupils, teachers, non-teaching staff, parents, and relatives, respectively (p=0.29).
Helsingen 2020 Local 11 individuals in the training arm (0.8% of those tested) and 27 in the non-training arm (2.4% of those those tested) tested positive for SARS-
CoV-2 antibodies (p=0.001)
Hobbs 2020 Local
Household
Community
Case-patients were significantly more likely to have had close contact with a person with known COVID-19 than control participants (aOR = 3.2,
95% CI = 2.0–5.0)
Case-patients were significantly more likely to have attended gatherings with persons outside their household, including social functions (aOR
= 2.4, 95% CI = 1.1–5.5), activities with children (aOR = 3.3, 95% CI = 1.3–8.4), or to have had visitors at home (aOR = 1.9, 95% CI = 1.2–2.9)
during the 14 days before the SARS-CoV-2 test.
Parents of 64% of case-patients and 76% of control participants reported that their child and all staff members wore masks inside the facility
(aOR = 0.4, 95% CI = 0.2–0.8).
Hu 2020 Household
Community
Household contacts were associated with a significantly larger risk of SARS-CoV-2 infection than other types of contact (P<0.001).
The transmission risk in the first generation was significantly higher than the later generations (p<0.001), possibly due to improved case
isolation and contacts quarantine that deplete the number of susceptible individuals in the cluster.
Hua 2020 Household Incidence of infection in child close contacts was significantly lower than that in adult contacts: 13.2% vs 21.2%, p=0.004
Islam 2020 Household
Local
Community
Nosocomial
The secondary attack rate among household contacts was at the highest risk of attack (13.04%, 95% CI 9.67-16.41) followed by funeral
ceremonies (8.33%, 95% CI 3.99-12.66) and family contacts (6.52%, 95% CI 4.02-9.02). The attack rate was higher in age groups 50–59 (10.89%,
95% CI 7.05-14.66) and 60–69 (9.09%, 95% CI 5.08-13.09)
Kawasuji 2020 Nosocomial Among symptomatic patients (n =18), the estimated viral load at onset was higher in the index than in the non-index patients (median [95%
confidence interval]: 6.6 [5.2–8.2] vs. 3.1 [1.5–4.8]. In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial
sample collection was significantly higher in the index than in the non-index patients (p = 0.02)
Khanh 2020 Community Seating proximity was strongly associated with increased infection risk (RR 7.3, 95% CI 1.2–46.2).
Laws 2020 Household There were no significant differences in secondary infection rates between adult and pediatric contacts among all households (OR: 1.11; 95%
CI: 0.56 to 2.21) or among households with children (OR: 0.99; 95% CI: 0.51 to 1.90).
Laxminarayan 2020 Local
Household
Community
Secondary attack rate estimates ranged from 1.2% (0.0 to 5.1%) in health care settings to 2.6% (1.6 to 3.9%) in the community and 9.0% (7.5 to
10.5%) in the household.
Lewis 2020 Household Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes
mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4–106.9) and 7.1 (95% CI: 1.2–42.5).
Household contacts of a male primary patient were more likely to have secondary infection than those of a female primary patient (SIR, 36% vs
18%; OR, 2.4; 95% CI, 1.1–5.3).
Li 2020d Household The secondary attack rate to children (aged <18 years) was 4% compared with 20.5% for adult members (odds ratio [OR], .18; 95% confidence
interval [CI], .06–.54; P = .002). The secondary attack rate to the contacts in the household with index patients quarantined at home
immediately since onset of symptoms was 0% compared with 18.3% for the contacts in the households without index patients quarantined
during the period between initiation of symptoms and hospitalization (OR, 0; 95% CI, .00–.00; p=0.000).
The secondary transmission rate for individuals who were spouses of index cases was 27.8% compared with 17.3% for other members in the
households (OR, 2.27; 95% CI, 1.22–4.22; p=0.010).
Liu 2020b Household
Community
Nosocomial
Compared to young adults aged 20–29 years, the infected risk was higher in children (RR: 2.59, 95%CI: 1.79–3.76), and old people aged 60–69
years (RR: 5.29, 95%CI: 3.76–7.46). People having close relationship with index cases encountered higher infected risk (RR for spouse: 20.68,
95%CI: 14.28–29.95; RR for non-spouse family members: 9.55, 95%CI: 6.73–13.55; RR for close relatives: 5.90, 95%CI: 4.06–8.59). Moreover,
contacts exposed to index case in symptomatic period (RR: 2.15, 95%CI: 1.67–2.79), with critically severe symptoms (RR: 1.61, 95%CI: 1.00–2.57)
Lopez Bernal 2020 Household
Community
Secondary attack rates were highest where the primary case was aged <18 years with a significantly higher odds of secondary infection (OR
61, 95% CI 3.3-1133).
Where the primary case was admitted to hospital there was a significantly lower odds of secondary infection in the household (OR 0.5, 95% CI
0.2-0.8).
Secondary attack rates were lower in larger households.
Luo 2020a Household
Community
Nosocomial
Household contacts had a significantly higher risk for secondary infection than did persons who were exposed in health care settings (OR,
0.09, 95%CI 0.04 to 0.20) or those who were exposed on public transportation (OR, 0.01, 95%CI, 0.00 to 0.08).
Macartney 2020 Local The rate of staff member to child transmission was lower (1·5%) than staff to staff transmission (4·4%).
Malheiro 2020 Household Among the intervention cohort,16 of 132 closecontacts tested positive during the follow-up period (attack rate:12.1%, 95% confidence interval
[CI]: 7.1-18.9). In the control cohort,138 of 1495 participants tested positive (attack rate: 9.2%, 95% CI:7.8-10.8)
Park 2020a Household
Non-household
With index patients 30–39 years of age as reference, detection of COVID-19 contacts was significantly higher for index patients >40 years of
age in nonhousehold settings.
Phiriyasart 2020 Household Locally religious and household contacts of confirmed cases had significantly higher risks of SARS-CoV-2 infection than other community
members.
Poletti 2020 Unclear Individuals younger than 70 years were at a significantly lower risk of death after infection than older patients (p<0.001). The risk of death was
62% lower (95% CI: 31–80%; p<0.001) during the second phase of the epidemic.
Razvi 2020 Nosocomial HCWs in patient facing roles had a significantly higher frequency of positive COVID-19 antibody tests (295/1302 [22.7%]) than those in non-
patient facing roles (88/669 [13.2%]), p<0.0001)
Rosenberg 2020 Household Prevalence significantly increased with age, ranging from 23% among those aged <5 years to 68% among those 65 years or older (p<0.0001)
Speake 2020 Aircraft The risk for secondary infections among passengers seated in the mid cabin was significantly greater than for those seated in the aft cabin
(p<0.005). The SAR among mid-cabin passengers in window seats was significantly greater than among those not in window seats (RR 5.2; 95%
CI 1.6–16.4; p<0.007).
Sun 2020 Household The family recurrence rate of spouses who introduced cases from the family was 63.87%, which was higher than the recurrence rate of
children (30.53%), parents (28.37%) and other family members (20.93%), and the difference was statistically significant ( P <0.001) .
Torres 2020 Community Antibody positivity rates were 9.9% (95%CI: 8.2-11.8) for 1,009 students and 16.6% (95%CI: 12.1-21.9) for 235 staff. Among students, positivity
was significantly associated with history of contact with a confirmed case (p<0.0001).
The greater the number of contacts, the greater the probability that a child was antibody positive (p=0.05).
van der Hoek 2020 Household In families of a confirmed COVID-19 patient, children between 1 and 11 years were less often positive in PCR and serology than older children
and adults.
Wang 2020b Household Face mask use by the primary case and family contacts before the primary case developed symptoms was 79% effective in reducing
transmission (OR=0.21, 95% CI 0.06 to 0.79). Daily use of chlorine or ethanol based disinfectant in households was 77% effective (OR=0.23,
95% CI 0.07 to 0.84). Wearing a mask after illness onset of the primary case was not significantly protective. The risk of household transmission
was 18 times higher with frequent daily close contact with the primary case (OR=18.26, 95% CI 3.93 to 84.79), and four times higher if the
primary case had diarrhoea (OR=4.10, 95% CI 1.08 to 15.60). Household crowding was not significant.
Wood 2020 Household Households without children had a significantly lower rate of COVID-19: HR per child 0.89; 95% CI 0.84–0.95. Households with childen had
higher rates of COVID-19 tests (9.2% vs 6.1%)
Compared to those in households without children, the risk of COVID-19 requiring hospitalisation was lower in those with one child and lower
still in those with two or more children: HR 0.72 per child (95% CI 0.60-0.85, p<0.001); adjusted for age - HR 0.83 per child (95% CI 0.70-0.99)
Wu 2020 Household
Local
Community
Contacts living in the same household as the index case had significantly higher risk of infection vs those who had only had brief contact with
the index case: RR 41.7 (17.7–98.5), p<0.001).
Contacts who had visited, or had contact with the index case in a medical institution had significantly higher risk of acquiring infection vs brief
contact with the index case: RR 3.6 (1.42–8.98), p=0.004.
Family members who had contact with an index case had significantly higher risk of infection vs healthcare providers or other patients who
had been exposed to an index case: RR 31.6 (7.69–130.01), p<0.001.
Those who had contact with the index case through work, through study, or in a place of entertainment had a significantly higher risk of
infection vs those who had contact with the index case in a medical institution: RR 6.7 (1.34–33.25), p=0.01.
Those who had contact with the index case in or near his/her home had a significantly higher risk of infection vs those who had contact with
the index case in a medical institution: RR 17.3 (4.20–70.77), p<0.001.
The incidence rate among those who wore face masks was significantly lower than that among those who did not use protective measures
(0.3% vs. 4.7%, respectively, p<0.001).
The incidence rate of contacts with data collected by field investigation was significantly higher than that of contacts with data collected by big
data (5.35% versus 0.07%, p<0.001).
Wu 2020a Household Contacts with >72 hours of exposure (SIR, 41.7%; [95% CI: 26.8%–58.3%]) had a higher SIR compared with those without (SIR, 23.2%; [95% CI:
11.4%–41.5%]). One household-level factor was significantly associated with SIR: household members without protective measures after illness
onset of the index patient (odds ratio [OR], 4.43; [95% CI: 1.37–14.34]).
Xin 2020 Household Increasing risk of infection among household contacts with female index patients (adjusted hazard ratio [aHR] = 3.84, 95% CI = 1.07–13.78),
critical disease index patients (aHR = 7.58, 95% CI = 1.66–34.66), effective contact duration with index patients > 2 days (aHR = 4.21, 95% CI =
1.29–13.73), and effective contact duration > 11 days (aHR = 17.88, 95% CI = 3.26–98.01)
Yu 2020 Household Family members, colleagues/classmates/travel companions, and doctors-patients accounted for 88.1% (1398), 10.7% (170), and 0.3% (5),
respectively. Following this order, the infection rate was 10.2%, 1.8% and 40.0%, respectively.
Yung 2020 Household Young children <5 years old were at lowest risk of infection (1.3%). Children were most likely to be infected if the household index case was the
mother.
Zhang 2020a Household
Local
Community
SAR among household contacts was 16.1% vs 1.1% for social contacts, and 0% for workplace contacts.
Older close contacts had the highest SAR compared with other age groups; 8.0% in persons >60 years of age compared with 1.4%–5.6% in
persons <60 years of age.
Close contacts that lived with an index case-patient had 12 times the risk for infection and those who had frequent contact with an index case-
patient, >5 contacts during 2 days before the index case was confirmed, had 29 times the risk for infection.
Zhuang 2020 Household
Community
The main sources of secondary infection were family exposure (74.5%, 178 cases), transportation exposure accounted for 8.4% (20 cases),
friend/colleague meal exposure accounted for 5.9% (14 cases). Shopping malls, markets, pharmacies and other public place exposure
accounted for 5.0% (12 cases), workplace exposure accounted for 3.8% (9 cases), and community exposure accounted for 2.5% (6 cases).

Viral culture

Three studies (Ladhani 2020a, Speake 2020, Yang 2020) performed viral culture ( Table 8). All studies utilised Vero E6 cells for viral culture. In Ladhani 2020a (a study of elderly nursing home residents), positive samples with a Ct of <35 were incubated on Vero E6 cells and confirmed by cytopathic effect (CPE) up to 14 days post-inoculation. Positive culture results were obtained for symptomatic, post-symptomatic, pre-symptomatic and asymptomatic cases (21 residents and 12 staff); higher Ct values was significantly associated with decreasing ability to recover the virus (p<0.001). Among residents the virus was isolated 12 days before symptom onset and up to 13 days after and in staff up to 6 days before and 7 days after symptom onset. In Speake 2020, specimens were inoculated in Vero-E6 cells and inspected for CPE daily for up to 10 days with identity confirmed using “in-house” PCRs. The primary cases had boarded the flight from a cruise ship and had SARS-CoV-2 with the strain A2-Ruby Princess (A2-RP). Nine of 17 (53%) of PCR-positive samples grew SARS-CoV-2 in culture. Eight secondary cases who were in the same flight cabin with the infected travellers from the cruise ship all had viruses of the A2-RP strain (3 by full and 1 by partial sequence) ( Table 8). In the third study of index patients with recurrent infection swab specimens were also inoculated on Vero cells, and monitored for CPE daily for 10 days (Yang 2020). All four viral cultures were negative (0%).

Table 8. Results of viral cultures.

Study ID Types of participants Method used for viral culture Results of viral culture
Ladhani 2020a Staff and residents of 6 London
care homes
All SARS-CoV-2 positive samples with a Ct value of
>35 were incubated on Vero E6 mammalian cells
and virus detection was confirmed by cytopathic
effect (CPE) up to 14 days post-inoculation
87 samples with Ct values <35 were cultured and infectious virus
was recovered from all (21 residents and 12 staff).
Live virus was isolated up to 13 days after and 12 days before
symptom onset among residents and up to 6 days before and 7
days after symptom onset among staff.
Higher Ct values was significantly associated with decreasing ability
to recover infectious virus (p<0.001).
There were no significant differences in virus recovery rates
between symptomatic and asymptomatic residents (5/17 [29.4%] vs.
14/33 [42.4%]; P = 0.37) and staff (2/6 [33.3%] vs. 10/31 [32.3%]; P =
0.96) at the time of testing.
Speake 2020 241 airline passengers some
of whom had disembarked
from 1 of 3 cruise ships that
had recently docked in Sydney
Harbour. 6 primary cases
initially
Virus culture was attempted for primary samples .
Clinical specimens were inoculated in triplicate
wells with Vero-E6 cells at 80% confluency,
incubated at 37°C in 5% CO2, and inspected for
cytopathic effect daily for up to 10 days. Identity
was confirmed by in-house PCRs as described for
previous sequences.
9/17 of PCR positive samples grew SARS-CoV-2 on viral culture.
Sufficient viral RNA was available to generate an adequate sequence
for 25 of the 29 samples positive by PCR.
11 passengers had PCR-confirmed SARS-CoV-2 infection and
symptom onset within 48 hours of the flight. All 11 passengers had
been in the same cabin with symptomatic persons who had culture-
positive A2-RP virus strain.
Yang 2020 Home quarantine: 93 recurrent-
positive patients; 96 close
contacts and 1,200 candidate
contacts
Vero-E6 cells were used for virus isolation in a BSL-
3 laboratory.
Viral culture of 4 specimens with Ct <30 were negative

Genome sequencing (GS) and phylogenetic analysis

Ten studies (Böhmer 2020, Firestone 2020, Jiang 2020, Ladhani 2020a, Lucey 2020, Pung 2020, Sikkema 2020, Speake 2020, Taylor 2020, Wang 2020) performed GS and phylogenetic analysis ( Table 9). The studies were primarily conducted in outbreak clusters and methods used for performing these investigations were essentially similar across the studies. The completeness of genomic similarity ranged from 81–100% across six studies (Firestone 2020, Jiang 2020, Lucey 2020, Sikkema 2020, Speake 2020, Wang 2020). Transmission from one case to a contact was demonstrated by nonsynonymous nucleotide polymorphism in SARS-CoV-2 from these two cases onwards, but not in any cases detected prior to this instance (Böhmer 2020). In one study of skilled nursing home facilities (Taylor 2020), samples from 75 residents and five healthcare staff shared genetically related strains. In another study of care homes (Ladhani 2020a), reported nine separate introductions of SARS-CoV-2 into care homes by healthcare staff. In one study which used multiple settings (Pung 2020), the viral genomic sequences for four cases in one cluster shared identical sequences over the full genome length and shared a common base difference relative to the earlier sequences (see Table 8).

Table 9. GS and phylogenetic analysis.

Study ID Study Setting Method used for WGS Phylogenetic analysis Results
Böhmer 2020 Home, workplace Whole genome sequencing involved
Roche KAPA HyperPlus library preparation
and sequencing on Illumina NextSeq
and MiSeq instruments as well as RT-PCR
product sequencing on Oxford Nanopore
MinION using the primers described in
Corman and colleagues. Patient 1 was
sequenced on all three platforms; patients
2–7 were sequenced on Illumina NextSeq,
both with and without RT-PCR product
sequencing with primers as in Corman
and colleagues; and patients 8–11, 14, and
16 were sequenced on Oxford Nanopore
MinION. Sequencing of patient 15 was not
successful. Sequence gaps were filled by
Sanger sequencing.
Not reported Presymptomatic transmission from patient 4 to patient 5 was strongly
supported by virus sequence analysis: a nonsynonymous nucleotide
polymorphism (a G6446A substitution) was found in the virus from
patients 4 and 5 onwards but not in any cases detected before this point
(patients 1–3). Later cases with available specimens, all containing this
same substitution, were all traced back to patient 5. The possibility that
patient 4 could have been infected by patient 5 was excluded by detailed
sequence analysis: patient 4 had the novel G6446A virus detected in a
throat swab and the original 6446G virus detected in her sputum, whereas
patient 5 had a homogeneous virus population containing the novel
G6446A substitution in the throat swab.
Firestone 2020 Motorcycle rally WGS was conducted at the MDH Public
Health Laboratory on 38 specimens using
previously described methods.
Phylogenetic relationships,
including distinct clustering of
viral whole genome sequences,
were inferred based on
nucleotide differences via
IQ-TREE using general time
reversible substitution models
as a part of the Nextstrain
workflow.
38 (73%) specimens (23 [61%] from primary and 15 [39%] from secondary
and tertiary cases) were successfully sequenced, covering at least 98%
of the SARS-CoV-2 genome. Six genetically similar clusters with known
epidemiologic links were identified (i.e., cases in patients who were
close contacts or who had common exposures at the rally), five of which
demonstrated secondary or secondary and tertiary transmission.
Jiang 2020 Home Positive samples were sequenced directly
from the original specimens as previously
described.
*Reference virus genomes were obtained
from GenBank using Blastn with 2019-
nCoV as a query. The open reading frames
of the verified genome sequences were
predicted using Geneious (version 11.1.5)
and annotated using the Conserved
Domain Database. Pairwise sequence
identities were also calculated using
Geneious. Potential genetic recombination
was investigated using SimPlot software
and phylogenetic analysis.
The maximum likelihood
phylogenetic tree of the
complete genomes was
conducted by using RAxML
software with 1000 bootstrap
replicates, employing the
general time-reversible
nucleotide substitution model.
The full genome of 8 patients were >99.9% identical across the whole
genome. Phylogenetic analysis showed that viruses from patients were
clustered in the same clade and genetically similar to other
SARS-CoV-2 sequences reported in other countries.
Ladhani 2020a Care homes Whole genome sequencing (WGS) was
performed on all RT-PCR positive samples.
Viral amplicons were sequenced using
Illumina library preparation kits (Nextera)
and sequenced on Illumina short-read
sequencing machines. Raw sequence data
was trimmed and aligned against a SARS-
CoV-2 reference genome (NC_045512.2).
A consensus sequence representing
each genome base was derived from the
reference alignment.
Consensus sequences were
assessed for quality, aligned
using MAFFT (Multiple Alignment
using Fast Fourier Transform,
version 7.310), manually curated
and maximum likelihood
phylogenetic trees derived using
IQtree (version 2.04).
All 158 PCR positive samples underwent WGS analysis and 99 (68
residents, 31 staff) distributed across all the care homes yielded sequence
sufficient for WGS analysis. Phylogenetic analysis identified informal
clusters, with evidence for multiple introductions of the virus into care
home settings. All care home clusters of SARS-CoV-2 genomes included at
least one staff member, apart from care home B with no PCR positive staff
and high rates of staff self-isolation. Care home A exhibited three distinct
sequence clusters and six singletons, potentially representing up to nine
separate introductions. Genomic analysis did not identify any differences
between asymptomatic/symptomatic residents/staff. The 10 sequences
from residents who died were distributed across the lineages identified
and were closely matched to sequences derived from non-fatal cases in
the same care homes.
Lucey 2020 Hospital Complementary DNA was obtained from
isolated RNA through reverse transcription
and multiplex PCR according to the
protocol provided by the Artic Network
initiative. Libraries were prepared using
the NEBNext Ultra II kit (New England
Biolabs) and sequenced on an Illumina
MiSeq using 300-cycle v2 reagent kits
(Illumina). Bowtie 2 was used for aligning
the sequencing reads to the reference
genome for SARS-CoV-2 (GenBank
number, MN908947.3) and SAMtools for
manipulating the alignments.
SNPs were used to define
clusters and a median-joining
network was generated
including these data from this
study and an additional 1,000
strains collected from GISAID
available on May 22nd. Clade
annotation was included for the
Pangolin, GISAID and NextStrain
systems.
WvGS identified six clusters of nosocomial SARS-CoV-2 transmission. The
average sequence quality per samples was > 99% for 46 samples, and
between 92 and 94% for 4 samples. Phylogenetic analysis identified six
independent groups of which clusters 1–3 were related to 39 patients.
Pung 2020 Multiple:
Company
conference,
church, tour
group.
Strain names, GISAID EpiCoV accession
numbers used for genomic sequencing
Phylogenetic tree utilised the
Neighbor-Joining method and
confirmed using Maximum
Likelihood approaches. Replicate
trees with bootstrap used. All
ambiguous positions were
removed for each sequence
pair (pairwise deletion option).
Evolutionary analyses were
conducted in MEGA X. Strain
names, GISAID EpiCoV accession
numbers and collection dates
are shown, followed by the case
number if available.
Cluster A: Viral genomic sequences were available for four cases (AH1,
AH2, AH3, and AT1) and phylogenetic analysis confirmed their linkage, as
suggested by the epidemiological data.
Sikkema 2020 Hospital Samples were selected based on a Ct
<32. A SARS-CoV-2-specific multiplex
PCR for nanopore sequencing was done.
The resulting raw sequence data were
demultiplexed using qcat. Primers were
trimmed using cutadapt,17 after which a
reference-based alignment to the GISAID
(Global Initiative on Sharing All Influenza
Data) sequence EPI_ISL_412973 was done
using minimap2. The consensus genome
was extracted and positions with a
coverage less than 30 reads were replaced
with N using a custom script using
biopython software (version 1.74) and the
python module pysam (version 0.15.3).
Mutations in the genome were confirmed
by manually checking the alignment, and
homopolymeric regions were manually
checked and resolved, consulting the
reference genome. Genomes were
included when having greater than 90%
genome coverage.
All available full-length SARS-CoV-2
genomes were retrieved from GISAID20
on March 20, 2020 (appendix 1 pp 8–65),
and aligned with the newly obtained
SARS-CoV-2 sequences in this study
using the multiple sequence alignment
software MUSCLE (version 3.8.1551).
Sequences with more than 10% of N
position replacements were excluded.
The alignment was manually checked
for discrepancies, after which the
phylogenomic software IQ-TREE (version
1.6.8) was used to do a maximum-
likelihood phylogenetic analysis, with the
generalised time reversible substitution
model GTR+F+I+G4 as best predicted
model. The ultrafast bootstrap option was
used with 1000 replicates. Clusters were
ascertained based on visual clustering and
lineage designations.
The code to generate
the minimum spanning
phylogenetic tree was written in
the R programming language.
Ape24 and igraph software
packages were used to write
the code to generate the
minimum spanning tree, and the
visNetwork software package
was used to generate the
visualisation. Pairwise sequence
distance (used to generate
the network) was calculated
by adding up the absolute
nucleotide distance and indel-
block distance. Unambiguous
positions were dealt with in a
pairwise manner. Sequences
that were mistakenly identified
as identical, because of transient
connections with sequences
containing missing data, were
resolved.
46 (92%) of 50 sequences from health-care workers in the study were
grouped in three clusters. Ten (100%) of 10 sequences from patients in the
study grouped into the same three clusters:
Speake 2020 Aircraft Processed reads were mapped to the
SARS-CoV-2 reference genome (GenBank
accession no. MN908947). Primer-
clipped alignment files were imported
into Geneious Prime version 2020.1.1
for coverage analysis before consensus
calling, and consensus sequences were
generated by using iVar version 1.2.2.
Genome sequences of SARS-
CoV-2 from Western Australia
were assigned to lineages
by using the Phylogenetic
Assignment of Named Global
Outbreak LINeages (PANGOLIN)
tool ( https://github.com/cov-lineages/pangolinExternal Link).
On July 17, 2020, we retrieved
SARS-CoV-2 complete genomes
with corresponding metadata
from the GISAID database.
The final dataset contained
540 GISAID whole-genome
sequences that were aligned
with the sequences from
Western Australia generated
in this study by using MAFFT
version 7.467. Phylogenetic
trees were visualized in iTOL
(Interactive Tree Of Life, https://
itol.embl.deExternal Link) and
MEGA version 7.014.
100% coverage was obtained for 21 and partial coverage (81%–99%) for 4
samples. The phylogenetic tree for the 21 complete genomes belonged to
either the A.2 (n = 17) or B.1 (n = 4) sublineages of SARS-CoV-2
Taylor 2020 Skilled
nursing
facilities
WGS was conducted by MDH-PHL on
available specimens using previously
described methods.
Phylogenetic relationships,
including distinct clustering of
viral whole genome sequences,
were inferred based on
nucleotide differences via
IQ-TREE, using general time
reversible substitution models
Specimens from 18 (35%) residents and seven (18%) HCP at facility A
were sequenced - Strains from 17 residents and five HCP were genetically
similar. At facility B, 75 (66%) resident specimens and five (7%) HCP
specimens were sequenced, all of which were genetically similar.
Wang 2020 Home Full genomes were sequenced using the
BioelectronSeq 4000. WGS integrated
information from 60 published genomic
sequences of SARS-CoV-2. Full-length
genomes were combined with published
SARS-CoV-2 genomes and other
coronaviruses and aligned using the FFT-
NS-2 model by MAFFT.
Maximum-likelihood
phylogenies were inferred under
a generalised-time-reversal
(GTR)+ gamma substitution
model and bootstrapped 1000
times to assess confidence using
RAxML.
The phylogenetic tree of full-length genomes showed that SARS-CoV-2
strains form a monophyletic clade with a bootstrap support of 100%.
Sequences from six HCWs in the Department of Neurosurgery and one
family member were closely related in the phylogenetic tree.
33 family members of the HCWs were not secondarily infected, due to the
strict self-quarantine strategies taken by the HCWs immediately after their
onset of illness, including wearing a facial mask when they came home,
living alone in a separated room, never eating together with their families.

Discussion

Summary of main findings

We identified 171 primary studies assessing the role of close contact in transmission of SARS-CoV-2. The evidence from these observational studies suggest that the risk of transmission is significantly increased through close contact with an infected case - the greater the frequency of contact, the greater the risk. Household contact setting is significantly more likely to result in transmission of SARS-CoV-2 compared to other types of contact settings. This risk of transmission appears to decrease with use of face masks and in cases where the index or primary cases are in the paediatric age group. The risk of close contact transmission is significantly increased in the elderly. Enclosed environments and social gatherings appear to increase the likelihood of close contact transmission. Close contact with persons having recurrent infection with SARS-CoV-2 is unlikely to result in transmission of the virus. There is wide heterogeneity in study designs and methods and the overall quality of evidence from published primary studies is sub-optimal. The results of systematic reviews also suggest that household contact setting increases the risk of transmission and being elderly is also associated with increased risks of transmission and mortality.

The positive results of viral cultures observed in two studies support the results of PCR and serologic tests showing that close contact setting was associated with transmission of SARS-CoV-2. The failure to successfully isolate the virus in the third study supports the view that individuals who are re-infected are unlikely to transmit the virus in close contact settings. The positive findings from all 10 studies that performed GS and phylogenetic analysis with identical strains supports the hypothesis that close contact setting is associated with SARS-CoV-2 transmission through respiratory droplets or direct contact. The failure of the majority of studies to report Ct values casts doubts on the strengths of any reported associations because of the likelihood of false positives, as is the lack of (and variation in) reporting of the timelines for sample collections. The variations observed in the definitions of close contacts also cast further doubts on the validity of overall results.

Comparison with the existing literature

The results of our review are consistent with several guidelines suggesting that close contact with index cases can result in transmission of SARS-CoV-2 810 . Our findings are also consistent with those of a systematic review which concluded that face masks are effective for preventing transmission of respiratory viruses 11 . The results of our review also support those of a previous review which showed that the elderly are at increased risk of infection and mortality with coronavirus 12 . However, our review contains a greater number of studies compared to each of the included individual reviews and shows evidence demonstrating positive culture of virus as well as genomic evidence of close contact transmission. This differs from the findings from our reviews of fomite, orofecal and airborne transmission that failed to show evidence of either positive culture or genomic sequences demonstrating SARS-CoV-2 transmission 1315 .

Strengths and limitations

To our knowledge, this is the most comprehensive review to date investigating the role of close contact in the transmission of SARS-CoV-2. We extensively searched the literature for eligible studies, accounted for the quality of included studies and have reported outcomes (viral culture and GS) that were previously unreported in previous reviews. However, we recognize some limitations. We may not have identified all relevant studies examining the role of close contact in transmission - this is especially true for unpublished studies. We included results from non-peer reviewed studies which may affect the reliability of the review results. However, such studies could potentially be of research benefit because of the ongoing pandemic; in addition, we performed forward citation search of relevant studies.

Implications for research

Future studies should endeavour to include Ct values (or preferably convert the Ct values to number of genome copies using standard curves) when reporting research results and should describe the timing and methods of sample collection. Details surrounding the proximity, timing, and activities within the context of close contact need to be described. In studies of elderly subjects, more detailed description of baseline demographics should be reported. Further studies showing virus isolation in close contact settings should be conducted to strengthen the current evidence base; this could include performing serial cultures. Similarly, more research examining genomic sequences and phylogenetic trees in suspected close contact transmissions should be conducted - this should also extend to research examining other modes of transmission. The variation in methods and thresholds of the serological tests add to the confusion about diagnostic accuracy of testing; indeed, some authors have questioned the value of serological tests for diagnosing SARS-CoV-2 16 . To overcome the challenge of interpreting antibody responses, guidelines for better reporting of serological tests and results should be developed; this has previously been emphasized by other authors. Internationally recognized research dictionary of terms defining and describing close contact settings should be developed. Standardized guidelines for reporting research results should be a priority. Local, national, and international health organisations should promote good hygiene measures including advising against close contact with SARS-CoV-2 infected individuals; use of medical masks should be encouraged in circumstances where close contact with infected cases is likely. Activities in enclosed settings should be discouraged and social distancing in close contact settings should be encouraged.

Conclusion

The evidence from published observational studies and systematic reviews indicate that SARS-CoV-2 can be transmitted via close contact settings. Household contact and increased frequency of contact with infected cases significantly increase the risk of transmission. The quality of evidence from published studies is low-to moderate. Variations in study designs and methodology restrict the comparability of findings across studies. Standardized guidelines for the reporting of future research should be developed.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

Extended data

Figshare: Extended data: SARS-CoV-2 and the Role of Close Contact in Transmission: A Systematic Review, https://doi.org/10.6084/m9.figshare.14312630.v1 6 .

This project contains the following extended data:

  • Updated Protocol

  • Search Strategy

  • List of Excluded Studies

  • References to Included Studies

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgements

This work was commissioned and paid for by the World Health Organization (WHO). Copyright on the original work on which this article is based belongs to WHO. The authors have been given permission to publish this article. The author(s) alone is/are responsible for the views expressed in the publication. They do not necessarily represent views, decisions, or policies of the World Health Organization.

Funding Statement

The review was funded by the World Health Organization: Living rapid review on the modes of transmission of SARs-CoV-2 reference WHO registration No2020/1077093. CH and ES also receive funding support from the NIHR SPCR Evidence Synthesis Working Group project 390.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

[version 1; peer review: 1 approved with reservations

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F1000Res. 2022 Apr 5. doi: 10.5256/f1000research.55716.r123867

Reviewer response for version 1

Richard Wamai 1

I have read this manuscript with keen interest and over several weeks during which COVID-19 has continued to evolve with new studies coming out and policy changes across countries I have been traveling in (Kenya and US). This manuscript deals with the question of availability of evidence for role of close contact in COVID-19 transmission. This question seems obvious now given 2+ years of generalized policy around the world for physical or social distancing. A lay observation would be to say that there is unequivocal evidence that close proximity has a role in the transmission of COVID (after all we have been told to distance). The authors of the present manuscript deal with the question of availability of scientific evidence for this generalized policy.

Clearly, a lot (if not all) of the NPIs (non-pharmaceutical interventions) have been implemented without evidence whether they work (Halperin DT, Hearst N, Hodgins S, et al. (2021) 1 - I am a co-author in this study. The current manuscript shows just how murky the state of evidence of these NPIs is. Consider the state of evidence of mask-wearing; just the Bangladeshi study is the only RCT we have, and the evidence that masks work from this trial is not that great (Abaluck J, Kwong LH, Styczynski A, et al., 2022 2 )

In my view, assessment of the merits of this manuscript should center on two things. The first is whether the authors have identified all the evidence available as published in scientific literature. The second is whether the authors make good-faith representation of the studies they have reviewed. I say “good-faith” because there are questions raised by the existing reviews and comments of this manuscript. Additionally, “good-faith” means to me that the authors have not omitted results from the studies. On these two accounts I write my recommendation. A systematic/scoping review is a unique type of study because authors should be presenting in good faith the information from the studies reviewed.

1. Have the authors examined all of the available evidence (=published studies) on the question?

The authors both say they have and have documented and included the method of their search for the literature reviewed (Appendix 2). The only problem I see with this is that studies reviewed were only those published as of December 20, 2020. That was the first full year of the pandemic. Publications from 2021 are not included. One would presume that it is more likely that more studies on the effect of distancing could have been conducted in 2021. Those studies are not included in this manuscript, and that is a shortcoming. One – and at the minimum necessary – revision that could be made is to add the timeframe of the review in the Title of the manuscript. In my view, it is not necessary for the authors to begin including the studies from 2021 as that would require a full new search and a re-write of large potions of the manuscript.

2. Have the authors presented truthfully and good-faith the evidence from the studies?

This is the central question for this manuscript, and it appears more so the case given the extensive comments by the readers. In my view, all of the criticism is not warranted. Criticism is due where the authors have not presented results from the studies reviewed truthfully and in good-faith. Criticism is also due where gaps in evidence is not acknowledged or are pertaining. I do not think the readers present counter evidence, i.e., show that the authors have summarized results from a specific study or set of studies erroneously. In the same vein I am not convinced that readers demonstrate that the authors have misinterpreted results from the studies they have reviewed; such misinterpretation would be strong grounds for Not Approving this manuscript or calling for its revisions, of course. If the readers are presenting evidence to counter the evidence from the studies presented by the authors from other studies that is acceptable. But that should also be weighed against my point 1 above. For instance, could the initial search have missed such studies raised by the readers?

Also, I would not engage in some of the debates presented. For instance, I do not think the manuscript should be criticized because “these authors may lack key expertise in their team”. I have read through the contributors’ listed expertise. I do not think any special expertise above and beyond what the author team has is needed to conduct a systematic review or truthfully and in good-faith summarize the evidence from the reviewed studies. In addition, I do not think that simply because persons in the author team are members of a decision-making body like the WHO that disqualifies them from objectivity or removes their training in science and scholarship. On the contrary, I think there is great value when decision-makers also participate in science. The obvious problem, of course, is where there are conflicts of interests, or where such persons are compromised. However, we have to take the consideration that in a multi-authored manuscript not one of the authors influences the entire narrative of the manuscript or results presented. Persons whose employment or affiliation positions may – or may be perceived to – compromise any perspectives presented in a manuscript they have co-authored should of course declare the conflicts of interests. Declaration of conflicts of interests is a standard protocol required in journal standards.

Having said the above, I have a few other observations or questions of my own.

Q1: On table 5, many studies are of no assessed quality, i.e., miss the quality measures specified in this table. What if studies missing all (or even just 2) of these measures are excluded in the analysis? So, if only those applicable as judged in Fig 2 are included.

Q2: On page 46, “Risk of Infection”. Is not ‘risk of infection’ similar to AR (attack rate) in the sense that AR reports risk of infection? In this section too (with Fig 3a) we would expect AR and SAR results to indicate risk of infection. Where, correspondingly, ARs and SARs are higher than risk of infection is high. Thus, risk of infection analysis do not present different results. Is this not how this should be understood?

Q3: “Implications for Research”, page 58. The text, "Local, national, and international health organisations should promote good hygiene measures including advising against close contact with SARS-CoV-2 infected individuals; use of medical masks should be encouraged in circumstances where close contact with infected cases is likely. Activities in enclosed settings should be discouraged and social distancing in close contact settings should be encouraged." -  To me, and objectively assessing the timing of the pandemic where we are today (April 1 st 2022), this text is mostly ‘water under the bridge’ and should thus be updated – if this manuscript is to be indexed. See discussions, e.g., in Halperin DT, Hearst N, Hodgins S, et al. (2021) 1 .

Additionally, I am not convinced the authors have presented compelling evidence here to warrant prompting such measures this text I highlight here include. The authors should strictly adhere to the evidence of their manuscript; it is wrong for the authors to echo the chorus of songs we have heard about these NPIs when there is no or limited evidence they work. Thirdly, as a further reason to exclude this concluding text, in this manuscript there is no discussion about hygiene. Evidence presented does not show close contact be avoided whatever the case. For instance, relevant studies reviewed show no transmission from (index) persons with previous repeated infection. Given this and the fact that by now many (if not most) people will have been infected (i.e., generalized spread) even multiple times (e.g., CDC. Nov. 16, 2021. Estimated COVID-19 Burden, https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html), should we still be advocating for quarantine and masking? We argue for adherence to evidence (Halperin DT, Hearst N, Hodgins S, et al., 2021 1 .

Finally, there will be a few grammatical errors that should be checked.

I am grateful for the opportunity to read this manuscript and share my observations which I hope will help guide the authors in determining merit worthiness for indexing as well as contribute to continued discussions.

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes

Is the statistical analysis and its interpretation appropriate?

Not applicable

Are sufficient details of the methods and analysis provided to allow replication by others?

Yes

Are the conclusions drawn adequately supported by the results presented in the review?

Yes

Reviewer Expertise:

Global public health

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

References

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F1000Res. 2022 Jun 29.
IGHO ONAKPOYA 1

Peer reviewer's comment: I have read this manuscript with keen interest and over several weeks during which COVID-19 has continued to evolve with new studies coming out and policy changes across countries I have been traveling in (Kenya and US). This manuscript deals with the question of availability of evidence for role of close contact in COVID-19 transmission. This question seems obvious now given 2+ years of generalized policy around the world for physical or social distancing. A lay observation would be to say that there is unequivocal evidence that close proximity has a role in the transmission of COVID (after all we have been told to distance). The authors of the present manuscript deal with the question of availability of scientific evidence for this generalized policy.

Authors' response: Thank you.

Peer reviewer's comment: Clearly, a lot (if not all) of the NPIs (non-pharmaceutical interventions) have been implemented without evidence whether they work (Halperin DT, Hearst N, Hodgins S, et al. (2021) 1 - I am a co-author in this study. The current manuscript shows just how murky the state of evidence of these NPIs is. Consider the state of evidence of mask-wearing; just the Bangladeshi study is the only RCT we have, and the evidence that masks work from this trial is not that great (Abaluck J, Kwong LH, Styczynski A, et al., 2022 2)

Authors' response: Thank you for this observation. As at the time we conducted the initial review, the evidence base was poor.

Peer reviewer's comment: In my view, assessment of the merits of this manuscript should center on two things. The first is whether the authors have identified all the evidence available as published in scientific literature. The second is whether the authors make good-faith representation of the studies they have reviewed. I say “good-faith” because there are questions raised by the existing reviews and comments of this manuscript. Additionally, “good-faith” means to me that the authors have not omitted results from the studies. On these two accounts I write my recommendation. A systematic/scoping review is a unique type of study because authors should be presenting in good faith the information from the studies reviewed.

Authors' response: Thank you for focusing your peer review on the evidence as presented in the manuscript.

Peer reviewer's comment: 1. Have the authors examined all of the available evidence (=published studies) on the question?

The authors both say they have and have documented and included the method of their search for the literature reviewed (Appendix 2). The only problem I see with this is that studies reviewed were only those published as of December 20, 2020. That was the first full year of the pandemic. Publications from 2021 are not included. One would presume that it is more likely that more studies on the effect of distancing could have been conducted in 2021. Those studies are not included in this manuscript, and that is a shortcoming. One – and at the minimum necessary – revision that could be made is to add the timeframe of the review in the Title of the manuscript. In my view, it is not necessary for the authors to begin including the studies from 2021 as that would require a full new search and a re-write of large potions of the manuscript.

Authors' response: We have updated the electronic searches up till 30/04/2022 because of the comments from reviewer #1 and re-written several aspects of the manuscript to reflect this update.

Peer reviewer's comment: 2. Have the authors presented truthfully and good-faith the evidence from the studies?

This is the central question for this manuscript, and it appears more so the case given the extensive comments by the readers. In my view, all of the criticism is not warranted. Criticism is due where the authors have not presented results from the studies reviewed truthfully and in good-faith. Criticism is also due where gaps in evidence is not acknowledged or are pertaining. I do not think the readers present counter evidence, i.e., show that the authors have summarized results from a specific study or set of studies erroneously. In the same vein I am not convinced that readers demonstrate that the authors have misinterpreted results from the studies they have reviewed; such misinterpretation would be strong grounds for Not Approving this manuscript or calling for its revisions, of course. If the readers are presenting evidence to counter the evidence from the studies presented by the authors from other studies that is acceptable. But that should also be weighed against my point 1 above. For instance, could the initial search have missed such studies raised by the readers?

Authors' response: We thank the reviewer for making this point. We agree with you that the criticisms were not justified. We searched, identified, and analyzed the available evidence at that time point.

Peer reviewer's comment: Also, I would not engage in some of the debates presented. For instance, I do not think the manuscript should be criticized because “these authors may lack key expertise in their team”. I have read through the contributors’ listed expertise. I do not think any special expertise above and beyond what the author team has is needed to conduct a systematic review or truthfully and in good-faith summarize the evidence from the reviewed studies. In addition, I do not think that simply because persons in the author team are members of a decision-making body like the WHO that disqualifies them from objectivity or removes their training in science and scholarship. On the contrary, I think there is great value when decision-makers also participate in science. The obvious problem, of course, is where there are conflicts of interests, or where such persons are compromised. However, we have to take the consideration that in a multi-authored manuscript not one of the authors influences the entire narrative of the manuscript or results presented. Persons whose employment or affiliation positions may – or may be perceived to – compromise any perspectives presented in a manuscript they have co-authored should of course declare the conflicts of interests. Declaration of conflicts of interests is a standard protocol required in journal standards.

Authors' response: Again, we agree with the reviewer. We have enough expertise in our team and have co-authored hundreds of systematic reviews.

Peer reviewer's comment: Having said the above, I have a few other observations or questions of my own.

Authors' response: Thank you. We have responded to each observation.

Peer reviewer's comment:  Q1: On table 5, many studies are of no assessed quality, i.e., miss the quality measures specified in this table. What if studies missing all (or even just 2) of these measures are excluded in the analysis? So, if only those applicable as judged in Fig 2 are included.

Authors' response: If we removed studies missing all or even 2 domains, we think the overall quality would still be low to moderate. Only 9 studies adequately dealt with bias.

Peer reviewer's comment:  Q2: On page 46, “Risk of Infection”. Is not ‘risk of infection’ similar to AR (attack rate) in the sense that AR reports risk of infection? In this section too (with Fig 3a) we would expect AR and SAR results to indicate risk of infection. Where, correspondingly, ARs and SARs are higher than risk of infection is high. Thus, risk of infection analysis do not present different results. Is this not how this should be understood?

Authors' response: The AR is a crude measure of the rate of infection in a group. The risk of infection compares the rate of attacks between or across groups, based on other variables, e.g., seating proximity. (See Box 1).

Peer reviewer's comment:  Q3: “Implications for Research”, page 58. The text, "Local, national, and international health organisations should promote good hygiene measures including advising against close contact with SARS-CoV-2 infected individuals; use of medical masks should be encouraged in circumstances where close contact with infected cases is likely. Activities in enclosed settings should be discouraged and social distancing in close contact settings should be encouraged." -  To me, and objectively assessing the timing of the pandemic where we are today (April 1st 2022), this text is mostly ‘water under the bridge’ and should thus be updated – if this manuscript is to be indexed. See discussions, e.g., in Halperin DT, Hearst N, Hodgins S, et al. (2021) 1.

Authors' response: We understand the point the reviewer makes. These statements were based on our understanding at that time. We have revised this section with the updated evidence. We have included the suggested reference.

Peer reviewer's comment: Additionally, I am not convinced the authors have presented compelling evidence here to warrant prompting such measures this text I highlight here include. The authors should strictly adhere to the evidence of their manuscript; it is wrong for the authors to echo the chorus of songs we have heard about these NPIs when there is no or limited evidence they work. Thirdly, as a further reason to exclude this concluding text, in this manuscript there is no discussion about hygiene. Evidence presented does not show close contact be avoided whatever the case. For instance, relevant studies reviewed show no transmission from (index) persons with previous repeated infection. Given this and the fact that by now many (if not most) people will have been infected (i.e., generalized spread) even multiple times (e.g., CDC. Nov. 16, 2021. Estimated COVID-19 Burden, https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burden.html), should we still be advocating for quarantine and masking? We argue for adherence to evidence (Halperin DT, Hearst N, Hodgins S, et al., 2021 1.

Authors' response: Thank you for raising this issue and we agree that we should stay focused on the evidence found in our review. We have accordingly revised the text as above.

Peer reviewer's comment: Finally, there will be a few grammatical errors that should be checked.

Authors' response: Thanks. We have re-checked the manuscript for grammatical errors.

Peer reviewer's comment: I am grateful for the opportunity to read this manuscript and share my observations which I hope will help guide the authors in determining merit worthiness for indexing as well as contribute to continued discussions.

Authors' response: Thank you for your helpful feedback which we believe has helped to improve the quality of the manuscript.

F1000Res. 2022 Mar 7. doi: 10.5256/f1000research.55716.r121151

Reviewer response for version 1

Kevin Escandón 1, Angela K Ulrich 2,3

General comments

We commend the authors for attempting to conduct a systematic review on one of the most controversial topics related to the COVID-19 pandemic: SARS-CoV-2 transmission. This is an important effort that required much dedication and careful analysis. Unfortunately, we think this manuscript falls short of scientific quality and utility due to major methodologic and conceptual flaws.

First, this systematic review in its current version fails to provide an accurate and updated picture of the existing evidence. We reviewed this manuscript in February 2022, two years into the pandemic, and while SARS-CoV-2 transmission remains a topic of great relevance, the picture regarding the modes of transmission is much clearer now than one year ago due to numerous epidemiologic and lab-based studies. Given this evidence, the WHO and the general scientific community agree that SARS-CoV-2 can be transmitted via droplet, short-range aerosol, long-range aerosol, and less frequently via fomites. This systematic review should be updated to reflect the most recent evidence. 

Second, and most importantly, there are methodological flaws, conceptual concerns, and unsupported conclusions, as detailed below. Systematic reviews are designed to summarize evidence on specific questions or focused problems with pre-defined criteria to bring understanding and clarity through insightful analyses (even if no meta-analyses are conducted) of existing evidence. Close contact is not only poorly defined in most articles, but is actually addressed in less than a half of the articles included. Importantly, close contact is not a transmission mechanism itself, rather a feature of transmission mechanism(s). The authors erroneously conclude that studies that identified identical strains in close contacts using genome sequencing and phylogenetic analysis support transmission via respiratory droplets. The authors do not acknowledge that short-range aerosol transmission is also a possible (and a likely one) explanation.

Note that given the absence of line numbers, we are not providing numbered comments.

Introduction

  • The introduction should be updated as statistics are over one year old (March 2021).

  • The authors mention that the “spread of the virus appears to be slowing”. This statement is not necessarily true considering the recent, recurring, and constantly evolving waves of infection attributed to increasingly transmissible variants of SARS-CoV-2. Furthermore, no citation is provided for this statement.

  • "Current evidence from epidemiologic and virologic studies suggest SARS-CoV-2 is primarily transmitted via respiratory droplets and direct and indirect contact". This sentence is not properly supported by current data; the authors rather cited two WHO 2021 resources. The authors must acknowledge airborne transmission – a route of transmission accepted by both WHO and CDC. Note that respiratory transmission of inhalable particles is the dominant mode of transmission, especially short-range. Indirect droplet / contact / fomite transmission is estimated to be minor.
    • Recommended references: Zhang & Duchaine 2020 1 and Leung 2021 2 .
  • The aim of this study is to assess the evidence from primary studies and existing systematic reviews investigating the role of close contact on SARS-CoV-2 transmission. This is aligned with the manuscript title ("SARS-CoV-2 and the role of close contact in transmission..."), the introduction, the methods, and figure and table titles. However, one major challenge is that the "close contact" framework is neither clearly defined in the literature nor is it often standardized in methods of primary studies. Authors address several aspects of transmission, from settings to distance, populations, testing/lab methods (PCR, serology, viral culture, GS and phylogenetic analysis), attack rates, risk of infection, etc. We agree that all of these are variables that influence or describe transmission. But close contact is only defined in 46.8% of included studies which causes concern over the use of consistently applied inclusion criteria. This systematic review seems to evaluate different aims and ends providing general descriptions of different subtopics related to transmission, not only to close contact. It is not appropriate for this study on the role of close contact to make such inference on the interaction between an infector and an infectee if not explicitly stated in the primary study.

Terminology

  • The authors seem to be using the CDC criteria but this is not clarified in the box definition and the citation link seems to be inadequate.

  • It should be "2 days prior to positive test" instead of "2 days prior to test specimen collection".

  • Some of the references are textbooks or web resources not easy to navigate or links are not active. Authors are encouraged to use the most relevant scientific articles on COVID-19 wherever possible.

  • Synonyms often used to close contact are close/short range and close proximity. The latter could be more beneficial since the word “contact” is often understood as physical and conspicuous encounters.

  • While it's understandable that definitions are needed to assess evidence, it is equally important to mention their limitations from the outset. For example, close contact is arbitrary for purposes of contact tracing—we know that the definition results in missing cases of exposure and infection at longer ranges.

Methods

  • The inclusion of articles identified via preprint servers is justifiable if the search criteria include very recent dates in an attempt to capture the most recent research. However, this systematic review only includes articles up to December 20th 2020 – if the authors choose to use this date or a recent one, articles on preprint servers should not be included.

  • The search strategy is not reproducible and more detail is required. For example, a detailed search strategy for the WHO COVID-19 database, LitCovid, medRxiv, and Google Scholar are not included in the Appendix 2. Nor is it clear exactly which keywords were used in the PubMed search, for example, were other terms used to capture the concept of duration and proximity of exposure?

  • It is not clear if authors defined “close contact” for inclusion in their systematic review.

Analyses of primary studies

  • Although authors have included extended data containing the protocol and references to included and excluded studies, this remains outdated (March 2021). Several features are discussed and while some of them could suggest close contact transmission, there is quite a bit of heterogeneity in how these studies of transmission inform the role of close contact.

  • While we agree that close-contact transmission is a dominant feature of SARS-CoV-2 transmission through the inhalation of respiratory particles, this systematic review does not help advance the aim mentioned - understanding the role of close contact. The authors could revise this work so it separately addresses features of transmission using standardized or limited definitions for each one. Attribution of such analyses to close contact (i.e., its potential role) should result from the interpretation of such findings altogether rather than from "direct assessment of the impact of close contact in transmission" since most studies do not define or measure close contact systematically.

Analyses of reviews

  • The authors included 10 systematic reviews allegedly investigating close-contact SARS-CoV-2 transmission. Some concerns make questionable the inclusion of such heterogeneous publications for an analysis that at best describes these almost individually without advancing the understanding of the role of close contact in SARS-CoV-2 transmission, which is the ultimate purpose of the authors' systematic review. It is expected that studies included in such publications are primarily observational, since randomized designs are complex and it remains unclear how research should ideally address gaps in our understanding of transmission. Findings of some of the included reviews (Li, Ludvigsson, Zhu) are not described with regard to close contact, but only to population groups; others are only mentioned with regard to asymptomatic infection or attack rates. We find this analysis in general unhelpful.

  • The authors analyze features different from close contact in the sections following "Primary studies". All these analyses are related to primary studies, so this should be reorganized for clarity. Again, there is a detailed description of studies that do not address close contact, e.g., "The result of one study (Rosenberg 2020) showed that the incidence of infection significantly increased with age (p<0.0001), while those from another study (Poletti 2020) showed that being 70 years or older was associated with a significantly increased risk of SARS-CoV-2-related death (p<0.001),"

Discussion

  • Authors should be careful in interpreting what their systematic review found, for instance that many studies report household transmission suggests that transmission occurs in indoor environments with higher exposure. Exposure results from concentration and time of contact with infectious respiratory particles. It, therefore, depends on a mix of frequency of contacts, range of contact, and infectiousness of index cases. But household transmission may perfectly encompass risk of infection beyond 3 m, 6 m, or any other definition of close contact. We do expect that the risk of infection is greatest with the longest contact, though, but the definition of a close contact remains nebulous and the associated risk could vary depending on the environmental conditions that favor transmission. Because the purpose of this systematic review is to address transmission, the authors must discuss at least generally the interplay of these factors. SARS-CoV-2 transmission is a complex phenomenon that depends on the interaction between viral properties (infectious dose and infectivity correlates), the host and their features (breathing rate, respiratory tract morphology, target tissues, receptor distribution, host barriers, immune responses), and the environment (temperature, humidity, salinity, pH, the medium or materials of the contaminated objects or surfaces, ventilation/airflow, ultraviolet radiation). Authors also should acknowledge that existing evidence suggests that transmission in close-contact settings is likely to be dominated by short-range respiratory inhalation of infectious virions.

  • The authors superficially mention the role of face masks in decreasing the risk of transmission from the pediatric population. This is a dangerous misinterpretation of evidence of two things that should be analyzed separately, i.e., 1) the efficacy of respiratory protection and 2) the risk of transmissibility from different populations. Certainly, this review was not designed to assess either of these aspects as a research question. As for respiratory protection, not all masks (or respirators) are expected to provide the same degree of protection. And if not correctly/consistently worn, they may not reduce risk. As for the usually overclaimed risk of children to transmit SARS-CoV-2, many potential confounders easily make this group appear highly contagious but it is unlikely this is due to intrinsic features of that population. Therefore, claims about it should be carefully framed to avoid stigmatization or unfair focalization and perceived efficacy of preventive strategies.

  • Discussion unrelated to close contact is seen, e.g., "being elderly is also associated with increased risks of transmission and mortality".

  • "The positive results of viral cultures observed in two studies support the results of PCR and serologic tests showing that close contact setting was associated with transmission of SARS-CoV-2".
    • We are unsure how this manuscript supports this conclusion. Similarly, this conclusion is not supported by the data "The positive findings from all 10 studies that performed GS and phylogenetic analysis with identical strains supports the hypothesis that close contact setting is associated with SARS-CoV-2 transmission through respiratory droplets or direct contact."
  • We agree with the authors on the high heterogeneity of existing studies and that "The variations observed in the definitions of close contacts also cast further doubts on the validity of overall results."

  • "The results of our review are consistent with several guidelines suggesting that close contact with index cases can result in transmission of SARS-CoV-2"
    • The authors acknowledge that the evidence for close contact transmission is only low-to-moderate quality, thus, it is a stretch to say that close contact is consistently demonstrated as a risk factor. Guidelines have been evolving throughout the pandemic and while close contact may be associated with increased risk of transmission, this study could provide much stronger evidence if transmission properties were assessed in a clearly defined, systematic, and reproducible way.
  • "Our findings are also consistent with those of a systematic review which concluded that face masks are effective for preventing transmission of respiratory viruses."
    • It is unclear how this systematic review regarding the role of close contract on transmission events contributes to the discussion regarding the role of face masks – more description is needed to make this link explicit. Furthermore, the efficacy of face masks is a complex topic and confounded by a number of factors.

Necessary updates

  • Several of the preprints included in the systematic review and/or cited in the manuscript have been published; given that this manuscript is outdated and an update is needed, authors should take that opportunity to update preprints that have been published and make sure their findings remain unchanged and adjust accordingly. Some of the preprints now published are:

    Helsingen 2020 3  

    Paireau 2020 4

    Kuwelker 2020 5  

    Lyngse 2020 6  

    Jones 2020 7  

    Chen 2020 8  

    Fontanet 2020 9

    Armann 2020 10  

    Charlotte 2020 11  

    Angulo-Bazan 2020 12  

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Partly

Is the statistical analysis and its interpretation appropriate?

Partly

Are sufficient details of the methods and analysis provided to allow replication by others?

No

Are the conclusions drawn adequately supported by the results presented in the review?

No

Reviewer Expertise:

Infectious diseases epidemiology, virology, public health.

We confirm that we have read this submission and believe that we have an appropriate level of expertise to state that we do not consider it to be of an acceptable scientific standard, for reasons outlined above.

References

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F1000Res. 2022 Jun 29.
IGHO ONAKPOYA 1

Peer reviewers, comment: We commend the authors for attempting to conduct a systematic review on one of the most controversial topics related to the COVID-19 pandemic: SARS-CoV-2 transmission. This is an important effort that required much dedication and careful analysis. Unfortunately, we think this manuscript falls short of scientific quality and utility due to major methodologic and conceptual flaws.

Authors' response: We thank the reviewers for their positive comments and constructive criticisms. We have extensively revised the manuscript to address their concerns.

Peer reviewers' comment: First, this systematic review in its current version fails to provide an accurate and updated picture of the existing evidence. We reviewed this manuscript in February 2022, two years into the pandemic, and while SARS-CoV-2 transmission remains a topic of great relevance, the picture regarding the modes of transmission is much clearer now than one year ago due to numerous epidemiologic and lab-based studies. Given this evidence, the WHO and the general scientific community agree that SARS-CoV-2 can be transmitted via droplet, short-range aerosol, long-range aerosol, and less frequently via fomites. This systematic review should be updated to reflect the most recent evidence.

Authors' response: The review was submitted in March last year at the start of the pandemic; however, it took a long time before undergoing peer review. We have now updated the review to reflect the most recent evidence focused on the transmission associated with close contact. We updated our searches up till 30/04/2022.

Peer reviewers' comment: Second, and most importantly, there are methodological flaws, conceptual concerns, and unsupported conclusions, as detailed below. Systematic reviews are designed to summarize evidence on specific questions or focused problems with pre-defined criteria to bring understanding and clarity through insightful analyses (even if no meta-analyses are conducted) of existing evidence. Close contact is not only poorly defined in most articles, but is actually addressed in less than a half of the articles included. Importantly, close contact is not a transmission mechanism itself, rather a feature of transmission mechanism(s). The authors erroneously conclude that studies that identified identical strains in close contacts using genome sequencing and phylogenetic analysis support transmission via respiratory droplets. The authors do not acknowledge that short-range aerosol transmission is also a possible (and a likely one) explanation.

Authors' response: We used the term “close contact settings” for our review, and we acknowledge variations in the definitions of close contact across the studies included in our review (see Table 3). We do not make any claims that close contact is a transmission mechanism but is associated with transmission from any of a number of mechanisms. We have added (with reference) that short-range aerosol transmission is a possible explanation for the identified identical strains in close contacts.

Peer reviewers' comment: Note that given the absence of line numbers, we are not providing numbered comments.

Authors' response: OK

Introduction

Peer reviewers' comment: 

  • The introduction should be updated as statistics are over one year old (March 2021).

The authors mention that the “spread of the virus appears to be slowing”. This statement is not necessarily true considering the recent, recurring, and constantly evolving waves of infection attributed to increasingly transmissible variants of SARS-CoV-2. Furthermore, no citation is provided for this statement.

Authors' response: We have updated the searches to April 2022.

We have provided a citation to show that the infection rate is decreasing ( https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19/latestinsights), and have also noted that the virus continues to evolve.

Peer reviewers' comment: 

  • "Current evidence from epidemiologic and virologic studies suggest SARS-CoV-2 is primarily transmitted via respiratory droplets and direct and indirect contact". This sentence is not properly supported by current data; the authors rather cited two WHO 2021 resources. The authors must acknowledge airborne transmission – a route of transmission accepted by both WHO and CDC. Note that respiratory transmission of inhalable particles is the dominant mode of transmission, especially short-range. Indirect droplet / contact / fomite transmission is estimated to be minor.
    • Recommended references: Zhang & Duchaine 2020 1 and Leung 2021 2.

Authors' response: We wish to thank the reviewer for this comment. We have updated the information and referenced the CDC and the WHO. The CDC statement suggests that exposure with infection occurs in 3 principal ways including inhalation of fine respiratory droplets, deposition of respiratory droplets and particles on exposed mucous membranes, splashes and sprays ‘and touching mucous membranes with hands soiled by virus contained in respiratory fluids” ( Scientific Brief: SARS-CoV-2 Transmission | CDC). They openly acknowledge the relative contributions of the modes of transmission outlined are unquantified and difficult to establish. We have revised the statement to state that the virus is primarily transmitted through exposure to infectious respiratory fluids such as fine aerosols, respiratory droplets, and added a further reference ( https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/sars-cov-2-transmission.html). The WHO states “available evidence continues to suggest that SARS-CoV-2 can spread from an infected person’s mouth or nose in small liquid particles when the person coughs, sneezes, sings, breathes or talks, by inhalation or inoculation through the mouth, nose or eyes. These liquid particles are different sizes, ranging from larger ‘respiratory droplets’ to smaller ‘aerosols." Current evidence suggests that the virus spreads mainly between people who are in close contact with each other, typically within 1 metre, They also indicate that “the virus can also spread to others through aerosols at longer (beyond the typical 1 metre distance) distances. The risk of long-distance aerosol transmission is higher in poorly ventilated and/or crowded indoor settings” and further discuss transmission through fomites but acknowledge data is limited. Similar to the CDC they indicate the many challenges in working out the presence and transmission of infectious viruses. Rather than state the respiratory transmission of inhalable particles is the dominant mode of transmission we would prefer a more cautious scientifically based response and acknowledge the gap in knowledge in this area. Infection prevention and control during health care when coronavirus disease (‎COVID-19)‎ is suspected or confirmed (who.int)

Peer reviewers' comment: 

  • The aim of this study is to assess the evidence from primary studies and existing systematic reviews investigating the role of close contact on SARS-CoV-2 transmission. This is aligned with the manuscript title ("SARS-CoV-2 and the role of close contact in transmission..."), the introduction, the methods, and figure and table titles. However, one major challenge is that the "close contact" framework is neither clearly defined in the literature nor is it often standardized in methods of primary studies. Authors address several aspects of transmission, from settings to distance, populations, testing/lab methods (PCR, serology, viral culture, GS and phylogenetic analysis), attack rates, risk of infection, etc. We agree that all of these are variables that influence or describe transmission. But close contact is only defined in 46.8% of included studies which causes concern over the use of consistently applied inclusion criteria. This systematic review seems to evaluate different aims and ends providing general descriptions of different subtopics related to transmission, not only to close contact. It is not appropriate for this study on the role of close contact to make such inference on the interaction between an infector and an infectee if not explicitly stated in the primary study.

Authors' response: We thank the reviewer for this comment to which we have thought a great deal. We can respond by stating that although only 46.8% (now 39.1%) defined close contact, the authors in the other included studies reported within their studies that they were investigating close contact. We acknowledge that not all studies provided precise definitions and that is a limitation. We set out to summarize the evidence from published studies that assess the association with close contact transmission in COVID-19.

As stated earlier, we have used the term “close contact settings” for our review.

Terminology

Peer reviewers' comment: 

  • The authors seem to be using the CDC criteria but this is not clarified in the box definition and the citation link seems to be inadequate.

Authors' response: Thanks. We have revised the definition.

Peer reviewers' comment: It should be "2 days prior to positive test" instead of "2 days prior to test specimen collection"

Authors' response: Thanks. We have revised the text accordingly.

Peer reviewers' comment: Some of the references are textbooks or web resources not easy to navigate or links are not active. Authors are encouraged to use the most relevant scientific articles on COVID-19 wherever possible

Authors' response: We have used the updated citations for the relevant articles.

Peer reviewers' comment: Synonyms often used to close contact are close/short range and close proximity. The latter could be more beneficial since the word “contact” is often understood as physical and conspicuous encounters.

Authors' response: We have broadly used “close contact setting” to allow us to capture the range of studies assessing transmission characteristics of SARS-CoV-2. We appreciate the reviewers’ suggestions of close proximity/range. However, these may be more useful for more focused review questions as they also have their limitations, e.g., direct contact would not be covered by these; however, direct contact has been described as a subset of close contact in some studies.

Peer reviewers' comment: 

  • While it's understandable that definitions are needed to assess evidence, it is equally important to mention their limitations from the outset. For example, close contact is arbitrary for purposes of contact tracing—we know that the definition results in missing cases of exposure and infection at longer ranges.

Authors' response: Thank you for this suggestion. We have noted this in the limitations section.

Peer reviewers' comment: 

  • The inclusion of articles identified via preprint servers is justifiable if the search criteria include very recent dates in an attempt to capture the most recent research. However, this systematic review only includes articles up to December 20th 2020 – if the authors choose to use this date or a recent one, articles on preprint servers should not be included.

Authors' response: We have updated the searches and used the most up-to-date citations for the included studies.

Peer reviewers' comment: The search strategy is not reproducible and more detail is required. For example, a detailed search strategy for the WHO COVID-19 database, LitCovid, medRxiv, and Google Scholar are not included in the Appendix 2. Nor is it clear exactly which keywords were used in the PubMed search, for example, were other terms used to capture the concept of duration and proximity of exposure?

Authors' response: Thank you. We have included the full search strategy.

Peer reviewers' comment: 

  • It is not clear if authors defined “close contact” for inclusion in their systematic review.

Authors' response: We used the CDC and WHO definitions (see Box 1).

Peer reviewers' comment: Additional detail is required to explain how the QUADAS-2 tool was adapted for this study and if or how it was validated for this purpose. https://figshare.com/articles/figure/Extended_data_SARS-CoV-2_and_the_Role_of_Close_Contact_in_Transmission_A_Systematic_Review/14312630/1?file=27243050

Authors' response: We did not use all the domains in QUADAS-2 and have clarified this in the manuscript methods section. We did not validate the checklist, and have noted this in our limitations.

Peer reviewers' comment: 

  • The QUADAS-2 tool was designed for studies primarily designed as diagnostic accuracy studies and its use is likely to fall short to assess the quality of studies for this systematic review.

Authors' response: QUADAS-2 is used to assess reporting quality in diagnostic reviews. See https://www.bristol.ac.uk/media-library/sites/quadas/migrated/documents/quadas2reportv4.pdf. As noted in our methods, we adapted the checklist for the review.

Analyses of primary studies

Peer reviewers' comment: 

  • Although authors have included extended data containing the protocol and references to included and excluded studies, this remains outdated (March 2021). Several features are discussed and while some of them could suggest close contact transmission, there is quite a bit of heterogeneity in how these studies of transmission inform the role of close contact.

Authors' response: We have updated the searches and included the most up-to-date citations.

Peer reviewers' comment: 

  • While we agree that close-contact transmission is a dominant feature of SARS-CoV-2 transmission through the inhalation of respiratory particles, this systematic review does not help advance the aim mentioned - understanding the role of close contact. The authors could revise this work so it separately addresses features of transmission using standardized or limited definitions for each one. Attribution of such analyses to close contact (i.e., its potential role) should result from the interpretation of such findings altogether rather than from "direct assessment of the impact of close contact in transmission" since most studies do not define or measure close contact systematically.

Authors' response: We included a table showing how the included studies defined close contact. Our objective was to identify, appraise and summarise the evidence from studies investigating transmission in close contact settings. It is equally possible that with close contact there may be transmission via large respiratory droplets and direct physical contact as well as the possibility of short-range fine aerosol and in all fairness, it should be stated as such and not that inhalation is the dominant route as this reviewer contends. It is best to be consistent with all possibilities as suggested by the CDC and WHO and many other publications.

Analyses of reviews

Peer reviewers' comment: 

  • The authors included 10 systematic reviews allegedly investigating close-contact SARS-CoV-2 transmission. Some concerns make questionable the inclusion of such heterogeneous publications for an analysis that at best describes these almost individually without advancing the understanding of the role of close contact in SARS-CoV-2 transmission, which is the ultimate purpose of the authors' systematic review. It is expected that studies included in such publications are primarily observational, since randomized designs are complex and it remains unclear how research should ideally address gaps in our understanding of transmission. Findings of some of the included reviews (Li, Ludvigsson, Zhu) are not described with regard to close contact, but only to population groups; others are only mentioned with regard to asymptomatic infection or attack rates. We find this analysis in general unhelpful.

Authors' response: Thanks for this comment. The included systematic reviews are considered appropriate since they do fit the definition of close contact based on our original protocol - this relates to structural and population settings. We can discuss the limitations of these reviews and the included studies. Li, Ludvigsson and Zhu fit the definitions. See https://www.ecdc.europa.eu/en/covid-19/surveillance/surveillance-definitions. Some of the findings from the reviews are helpful. Indeed at least 2 reviews included only studies with high reporting quality.

Peer reviewers' comment: 

  • The authors analyze features different from close contact in the sections following "Primary studies". All these analyses are related to primary studies, so this should be reorganized for clarity. Again, there is a detailed description of studies that do not address close contact, e.g., "The result of one study (Rosenberg 2020) showed that the incidence of infection significantly increased with age (p<0.0001), while those from another study (Poletti 2020) showed that being 70 years or older was associated with a significantly increased risk of SARS-CoV-2-related death (p<0.001),"

Authors' response: Thank you for pointing this out and we have revised the section on primary studies. We have enumerated the definitions of close contacts in the included studies in Table 3 and reported that several studies did not report a definition). Several studies showed that being elderly was significantly associated with increased risk of infection. Rosenberg 2020 included household contacts. We have revised the statement.

Discussion

Peer reviewers' comment: 

  • Authors should be careful in interpreting what their systematic review found, for instance that many studies report household transmission suggests that transmission occurs in indoor environments with higher exposure. Exposure results from concentration and time of contact with infectious respiratory particles. It, therefore, depends on a mix of frequency of contacts, range of contact, and infectiousness of index cases. But household transmission may perfectly encompass risk of infection beyond 3 m, 6 m, or any other definition of close contact. We do expect that the risk of infection is greatest with the longest contact, though, but the definition of a close contact remains nebulous and the associated risk could vary depending on the environmental conditions that favor transmission. Because the purpose of this systematic review is to address transmission, the authors must discuss at least generally the interplay of these factors. SARS-CoV-2 transmission is a complex phenomenon that depends on the interaction between viral properties (infectious dose and infectivity correlates), the host and their features (breathing rate, respiratory tract morphology, target tissues, receptor distribution, host barriers, immune responses), and the environment (temperature, humidity, salinity, pH, the medium or materials of the contaminated objects or surfaces, ventilation/airflow, ultraviolet radiation). Authors also should acknowledge that existing evidence suggests that transmission in close-contact settings is likely to be dominated by short-range respiratory inhalation of infectious virions.

Authors' response: Thank you. We have enumerated the complex range of factors at play and the epidemiologic associations in relation to close contact transmission (with references) and have acknowledged the various potential modes of transmission. We agree that transmission is a complex phenomenon and indeed is poorly understood. Musing about issues surrounding the biology of virus particles is beyond the scope of our review which focuses on epidemiologic associations.

Peer reviewers' comment: The authors superficially mention the role of face masks in decreasing the risk of transmission from the pediatric population. This is a dangerous misinterpretation of evidence of two things that should be analyzed separately, i.e., 1) the efficacy of respiratory protection and 2) the risk of transmissibility from different populations. Certainly, this review was not designed to assess either of these aspects as a research question. As for respiratory protection, not all masks (or respirators) are expected to provide the same degree of protection. And if not correctly/consistently worn, they may not reduce risk. As for the usually overclaimed risk of children to transmit SARS-CoV-2, many potential confounders easily make this group appear highly contagious but it is unlikely this is due to intrinsic features of that population. Therefore, claims about it should be carefully framed to avoid stigmatization or unfair focalization and perceived efficacy of preventive strategies.

Authors' response: We do not believe we are being superficial but rather trying to stay true to the findings. Our statements regarding the effectiveness of face masks are based on the findings from the included studies and we need to stay focused on the findings and avoid making speculative statements. We have added a caveat that there is uncertainty about the extent to which the different types of masks influence the risk of transmission.

Peer reviewers' comment: Discussion unrelated to close contact is seen, e.g., "being elderly is also associated with increased risks of transmission and mortality".

Authors' response: Thank you for pointing this out. We have removed the statement.

Peer reviewers' comment: 

  • The positive results of viral cultures observed in two studies support the results of PCR and serologic tests showing that close contact setting was associated with transmission of SARS-CoV-2".
    • We are unsure how this manuscript supports this conclusion. Similarly, this conclusion is not supported by the data "The positive findings from all 10 studies that performed GS and phylogenetic analysis with identical strains supports the hypothesis that close contact setting is associated with SARS-CoV-2 transmission through respiratory droplets or direct contact."

Authors' response: We have revised the statement to indicate that transmission can occur in close contact settings.

Peer reviewers' comment: We agree with the authors on the high heterogeneity of existing studies and that "The variations observed in the definitions of close contacts also cast further doubts on the validity of overall results."

Authors' response: Thank you.

Peer reviewers' comment: 

  • "The results of our review are consistent with several guidelines suggesting that close contact with index cases can result in transmission of SARS-CoV-2"
    • The authors acknowledge that the evidence for close contact transmission is only low-to-moderate quality, thus, it is a stretch to say that close contact is consistently demonstrated as a risk factor. Guidelines have been evolving throughout the pandemic and while close contact may be associated with increased risk of transmission, this study could provide much stronger evidence if transmission properties were assessed in a clearly defined, systematic, and reproducible way.

Authors' response: Thank you for this comment. We have revised the sentence to discuss the “association” with transmission as opposed to "can result in transmission”. We have added a caveat to note that guidelines keep evolving based on emerging evidence.

Peer reviewers' comment: 

  • "Our findings are also consistent with those of a systematic review which concluded that face masks are effective for preventing transmission of respiratory viruses."

It is unclear how this systematic review regarding the role of close contract on transmission events contributes to the discussion regarding the role of face masks – more description is needed to make this link explicit. Furthermore, the efficacy of face masks is a complex topic and confounded by a number of factors.

Authors' response: We have revised the statements. We have deleted the texts relating to mortality in the elderly.

Peer reviewers' comment:  Necessary updates

  • Several of the preprints included in the systematic review and/or cited in the manuscript have been published; given that this manuscript is outdated and an update is needed, authors should take that opportunity to update preprints that have been published and make sure their findings remain unchanged and adjust accordingly. Some of the preprints now published are:

    Helsingen 2020 3

    Paireau 2020 4

    Kuwelker 2020 5

    Lyngse 2020 6

    Jones 2020 7

    Chen 2020 8

    Fontanet 2020 9

    Armann 2020 10

    Charlotte 2020 11

    Angulo-Bazan 2020 12

Authors' response: Thank you. We have now updated the citations for the references.

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Data Availability Statement

    Underlying data

    All data underlying the results are available as part of the article and no additional source data are required.

    Extended data

    Figshare: Extended data: SARS-CoV-2 and the Role of Close Contact in Transmission: A Systematic Review, https://doi.org/10.6084/m9.figshare.14312630.v1 6 .

    This project contains the following extended data:

    • Updated Protocol

    • Search Strategy

    • List of Excluded Studies

    • References to Included Studies

    Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).


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