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PLOS One logoLink to PLOS One
. 2024 Mar 11;19(3):e0271848. doi: 10.1371/journal.pone.0271848

COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?

Jakob Schumacher 1,2,*, Lisa Kühne 3, Sophia Brüssermann 3, Benjamin Geisler 4, Sonja Jäckle 4
Editor: Emanuele Crisostomi5
PMCID: PMC10927113  PMID: 38466677

Abstract

Isolating COVID-19 cases and quarantining their close contacts can prevent COVID-19 transmissions but also inflict harm. We analysed isolation and quarantine orders by the local public health agency in Berlin-Reinickendorf (Germany) and their dependence on the recommendations by the Robert Koch Institute, the national public health institute. Between 3 March 2020 and 18 December 2021 the local public health agency ordered 24 603 isolations (9.2 per 100 inhabitants) and 45 014 quarantines (17 per 100 inhabitants) in a population of 266 123. The mean contacts per case was 1.9. More days of quarantine per 100 inhabitants were ordered for children than for adults: 4.1 for children aged 0-6, 5.2 for children aged 7-17, 0.9 for adults aged 18-64 and 0.3 for senior citizens aged 65-110. The mean duration for isolation orders was 10.2 and for quarantine orders 8.2 days. We calculated a delay of 4 days between contact and quarantine order. 3484 contact persons were in quarantine when they developed an infection. This represents 8% of all individuals in quarantine and 14% of those in isolation. Our study quantifies isolation and quarantine orders, shows that children had been ordered to quarantine more than adults and that there were fewer school days lost to isolation or quarantine as compared to school closures. Our results indicate that the recommendations of the Robert Koch Institute had an influence on isolation and quarantine duration as well as contact identification and that the local public health agency was not able to provide rigorous contact tracing, as the mean number of contacts was lower than the mean number of contacts per person known from literature. Additionally, a considerable portion of the population underwent isolation or quarantine, with a notable number of cases emerging during the quarantine period.

Introduction

Separation orders for cases (isolation) and for contacts (quarantine) are public health interventions to slow down the spread of COVID-19. Both are recommended by the WHO [1] and both are serving as an integral part of the COVID-19 response [2]. While isolation and quarantine orders are critical in controlling the spread of COVID-19, they are not without adverse effects. These measures involve restricting individuals’ freedom, often leading to psychological distress, social isolation, and broader socio-economic challenges [35]. It is essential to weigh these drawbacks against the benefits in the overall strategy against COVID-19. Other important measures where school closures, that were mandated by the federal states. In Berlin, schools were closed for 124 days, spanning from March 13 to May 29, 2020, and January 6 to February 22, 2021.

COVID-19 is caused by SARS-CoV-2, a virus that emerged in 2019 in China, likely by a zoonotic spillover [6]. Since then it has spread all over the world and caused a pandemic. The disease is spread from human to human. It is a respiratory disease with a pathway via the ACE-2-receptor, that can range from asymptomatic cases to severe respiratory infections and death [7]. Vaccines have been developed and proven successful in inducing seroconversion [8], preventing severe disease and death [9], but vaccine hesitancy hinders the effectiveness [10]. Novel drugs have been developed, some of which are useful, especially for individuals with a high risk [11].

The legal framework in Germany for isolation and quarantine orders is outlined in § 28–30 of the infection protection act. The national institute for public health, the Robert Koch Institute, recommends a duration for the isolation and quarantine period and provides a definition for contact persons [12, 13]. The 16 federal states of Germany have legal frameworks for contact tracing that usually follow the recommendations of the Robert Koch Institute. There are 378 local public health agencies that execute the isolation and quarantine orders for cases and contacts, respectively. Some local public health agencies, including Berlin-Reinickendorf, issued a general decree for isolation and quarantine, following the national and federal state laws. The local public health agency of Berlin-Reinickendorf established an internal guideline document (“Reinickendorfer Coronavirus Update”) that harmonised the work of the staff and specified the aforementioned law documents.

The local public health agency Berlin-Reinickendorf is responsible for a district of Berlin with about 1/4 million inhabitants. Before the COVID-19 pandemic, the infectious disease unit of the agency consisted of 9 persons. During the pandemic, up to 140 persons were working on contact tracing and case isolation at a time. The additional staff consisted mainly of staff from district and state agencies, containment scouts from an initiative by the Robert Koch Institute and soldiers from the German military force. The incidence of COVID-19 in Berlin-Reinickendorf followed the wave pattern for Germany as a whole. Due to the high work load the agency was not able to uphold contact tracing starting from December 2021. The local public health agencies of Berlin were working in close collaboration: throughout most of the time, the local public health agency of Berlin-Reinickendorf managed all contacts from Berlin, that resulted from cases in Berlin-Reinickendorf, but when a contact turned positive, the case was managed in the district where the person was living.

Available literature that directly analyse field work on isolation and quarantine orders are scarce. In the United States of America, two studies analysed a student initiative that traced 953 contacts of 536 COVID-19 cases around Pennsylvania [14, 15] and Sachdev et al. analysed the tracing of 1214 contacts of 1633 cases in San Francisco [16]. Shi et al. analysed 183 cases and their 1983 close contacts in Whanzou, China in much detail [17] and Jian et al. reported on the Taiwanese digital system TRACE analysing 487 cases and 8051 contact persons [18]. Public health implications of these systems included surveillance of travel history [19] and ensuring an adequate quantity of personal protective equipment [20]. Mossong et al. traced 2721 contacts of 424 cases in schools in Luxemburg, resulting in an average quarantine duration of 4.3 days for pupils. The proportion of quarantined persons that turned out to be secondary cases depended on the setting where the transmission took place. Within schools, 2.2% of pupils and 1.1% of teachers got infected after contact to a case, while transmission within families occurred for 14% of contacts [21]. According to existing literature, the average person in Germany typically has about 7.95 contacts per day [22].

The goal of this work is to quantify and analyse isolation and quarantine orders from a local public health agency in Germany to assess differences among age groups, mean number of contacts, timeliness of quarantine orders, the number of contained or non-contained cases and to estimate the impact of the contact person tracing. In addition, we evaluate the influence of the recommendations of the Robert Koch Institute on the number and duration of isolation and quarantine orders. The results are intended to support decisions by health authorities regarding the revisions of recommendations for current and future outbreaks. To the best of our knowledge, this is the first study in Germany that analyses field work on isolation and quarantine orders and the largest analysis worldwide that covers nearly two years of the pandemic.

Methods

Contact tracing and quarantine strategy

After the notification of a case the staff of the local public health agency contacted the case and identified individuals who had been in close contact with the case, where the definition of “close contact” was taken from the recommendations of the Robert-Koch-Institute. Once identified, these contacts were placed under quarantine. During the quarantine period the individuals were instructed to regularly check and report symptoms indicative of COVID-19. To optimize the use of testing resources for conducting PCR tests, the staff employed a scoring system, termed ‘Abstrichscore.’ This system prioritized individuals based on several criteria, with contact persons typically receiving the highest scores, especially when exhibiting symptoms. Consequently, during the study persiod nearly all contact persons were selected for testing.

Data retrieval and cleaning, inclusion and exclusion criteria and handling of missing data

The population under study consisted of all people residing in Berlin Reinickendorf and had a separation order in the study period. The study period ranged from the time of notification of the first case, the 3 March 2020, until the 18 December 2021, when the local public health agency was unable to continue recording contacts due to the high number of cases. Our data on isolation and quarantine orders were retrieved on 10 February 2022 from the database of separation orders of the reporting software of the agency. (SurvN et@RKI [23]). The following variables were extracted from the list of isolation orders as well as the quarantine orders: beginning of separation order, end of separation order, reporting date, age group (0–6, 7–17, 18–59, 60–110 years). We generated a person ID in Microsoft Excel consisting of name, surname, date of birth and the address directly after the export. Personal data and the links to the person ID were subsequently deleted and the—now anonymous—person ID and the remaining data was exported to be used in the programming language R [24]. Entries with missing values in one of the date variables for separation orders were not included. We defined a separation order as a record in the study period with an anonymous person ID that indicate an existing person. Entries with presumed typing errors in one of the date variables were removed. A typing error was assumed in case 1) any date was not between 3 March 2020 and 1 January 2022 (the end of the study period plus 14 days), 2) the separation order was longer than 30 days or less than one day or, 3) the beginning of the separation order was more than 182 days (half a year) before the reporting date or more than 182 days after the reporting date. We merged double entries when a person was assumed to have two overlapping isolation periods or two overlapping quarantine periods. In this case, the beginning of the combined period was set to the earlier date of the two start dates and the end of the combined period was set to the later of the two end dates. The non-merged entry was removed as a duplicate. If a quarantine period had an overlap with an isolation period, we set the end of a quarantine period to the date of the beginning of the isolation period.

We retrieved demographic data from the Open Data Portal Berlin. We used the latest available data from the year 2020 [25]. We retrieved the total number (Nall), as well as the number of kindergarten children aged 0 to 6 (N0–6), school children aged 7 to 17 (N7–17), adults aged 18 to 64 (N18–64) and senior citizens aged 65 to 110 (N64–110).

Analysis of recommendations

We analysed relevant changes in the definition of contact persons [13] (contact person definition period or C), changes in the recommended duration of isolation (isolation duration period or I) and changes in the recommended duration of quarantine (quarantine duration period or Q) [12] during the study period. The data were retrieved from the website of the Robert Koch Institute, the archives of the website of the Robert Koch Institute on the Waybackmachine and the internal guideline document (“Reinickendorfer Coronavirus Update”). We considered changes as relevant when they were mentioned in the guidelines of the local public health agency or were deemed as important by the staff thereof.

Statistical measures

We calculated the following measurements

  • Quantity of isolation and quarantine orders: The total number of isolation ni and quarantine nq orders (in total, by age group and by contact person definition period). The number of isolation orders per 100 inhabitants ni-p100 and quarantine orders per 100 inhabitants nq-p100 (in total and by age group). We counted how many separation orders were given for an individual nper-individual.

  • Duration of isolation and quarantine orders: The mean (d˜i) and median (di) duration and the interquartile range of isolation and quarantine orders (d˜q, dq, respectively) in total, by age group and by isolation duration or quarantine duration. We also calculated the number of days spent in isolation or quarantine order per inhabitant (ndi-pi or ndq-pi) in total and by age group. We calculated the duration as the difference between the end of the separation order and the beginning of the separation order plus one day, because the separation order included the last day.

  • Ratio of quarantines to isolation orders: We divided the number of quarantine orders by the number of isolation orders rqi in total or by period of recommendation for the definition of contact persons. For this calculation, we used only entries where the beginning of the separation order was after the 24 May 2020, because contact persons were not recorded in SurvNet prior to that date. Note that we were not able to link a contact person directly to the case with whom she or he was in contact, as the agency did not record these links in the software.

  • Number of quarantine orders that had a following isolation order: For separation orders issued after May 24, 2020, we categorized cases into three scenarios: 1) Isolation orders immediately following quarantine, termed ‘contained cases’ ncc e.g. a person that developed COVID-19 while being in quarantine—2) Isolation orders within 7 days post-quarantine, labeled ‘non-contained cases’—we refer to this as a non-contained case nncc, e.g. a person that was in quarantine, got out of quarantine and then developed COVID-19 within 7 days. We chose the cut-off value of 7 because it marks half of the incubation period or 3) persons with no isolation order in the seven days following a quarantine order, retrospectively unnecessary quarantines. We calculated these numbers overall and stratified by age group, contact person definition period and quarantine duration periods.

  • Timeliness of isolation and quarantine orders: For periods with a recommended quarantine duration of 14 days we approximated the time delay between the last day of contact and the beginning of the quarantine order d˜delay. We subtracted the length of the quarantine order from 14 days.
    d˜delay=14-d˜q (1)

    The ‘last contact’ refers to the date when an individual was last at risk of infection, as determined by the local public health staff. In houshold situations, this was marked by the date when the health agency staff advised the individual to start separating from the infected person.

Reproducibility, ethics statement and data protection

The corresponding script as well as the anonymous data set are available on Github [26]. This work was conducted as part of the surveillance work of the local public health agency. Institutional review board approval and informed consent were not required. Data protection approval was given by the local agency data protection unit.

Results

Results of data retrieval and cleaning

We extracted 109 087 database entries from SurvNet. We removed several entries that did not fulfil the case definition. These included 11 215 entries with missing dates, 108 entries with an invalid ID and 24 030 entries where the separation order did not begin within the study period. We also removed 377 entries because they had a presumed typing error in one of the dates as well as 30 duplicated isolation orders and 2498 duplicated quarantine orders. We analysed 70 829 entries. For a graphical overview see S1 Fig. For 3484 quarantines we reduced the length by the overlap with a following isolation period. In the demographic data we found 266 123 inhabitants registered in Berlin-Reinickendorf.

Results of the analysis of recommendations

We analysed changes in case definitions, isolation and quarantine duration both in the recommendations given by the Robert Koch Institute and the internal guidelines of the local public health agency Berlin-Reinickendorf during the study period. We identified three periods with relevant differences in isolation duration (denoted as I1–3), four periods with relevant differences in quarantine duration (denoted as Q1–4) and three periods with relevant differences in contact person definition (denoted as C1–3). The internal guideline document closely followed the recommendations of the Robert Koch Institute, except for one change in contact person definition regarding schools and kindergartens. Main differences for isolation and quarantine duration included the length of the recommended time period and whether a negative test could be used to end the isolation or quarantine early, either with an antigen or a PCR test. The main differences in the contact person definition were the length of the face-to-face contact that led to a separation order, the way of regarding children in large groups as contact persons (group quarantine, e.g., the whole class was ordered to quarantine or individual quarantine, e.g., only the persons with a direct contact were ordered to quarantine) and if vaccinated or recovered persons were given a separation order. An overview of the time periods is shown in Table 1 and with more detail and with an excerpt from the original source and corresponding links in the S1 Table.

Table 1. Time periods of relevant recommendations of the Robert Koch Institute for isolation duration, quarantine duration and contact person definition.

Isolation duration period
from until recommended duration
I1 03.03.2020 01.07.2020 14 days
I2 02.07.2020 30.03.2021 10 days (with PoC)
I3 31.03.2021 18.12.2021 14 days
Quarantine duration period
from until recommended duration
Q1 03.03.2020 30.11.2020 14 days
Q2 01.12.2022 15.02.2021 10 days (with PoC)
Q3 16.02.2021 08.09.2021 14 days
Q4 09.09.2021 18.12.2021 7 days (with PoC); 5 days (with PCR/children with PoC)
Contact person definition period
from until time definition + Group/individual + Vacc. status
C1 03.03.2020 30.03.2021 15 min. + children with GQ
C2 31.03.2021 19.05.2021 10 min. + children with GQ + not vacc.
C3 20.05.2021 18.12.2021 10 min. + children with IQ + not vacc.

PoC = Point of care or antigen test, PCR = Polymerase-chain-reaction test, GQ = group quarantine, where usually a complete group of children was ordered to quarantine, IQ = individual quarantine where usually individual children with direct contact were ordered to quarantine, not vacc. = vaccinated or recovered persons were not ordered to quarantine.

Results of statistical measures

Analysis of quantity of isolation and quarantine orders

The local public health agency ordered ni = 24 433 isolations and nq = 45 335 quarantines (ni-p100 = 9.2 isolation orders and nq-p100 = 17 quarantine orders per 100 inhabitants). The distribution over time is shown in Fig 1. The number of isolation and quarantine orders by age group and contact person definition period can bee seen in Table 2. The number of quarantines per 100 inhabitants nq-p100 was 50.6 for kindergarten children and 64.9 for school children as compared to 10.5 in adults and 3.2 in the senior citizens group. Thus school children were 20.3 times more likely to have been in quarantine than senior citizens. 46 817 (81.5%) persons had one separation order (either isolation or quarantine), 9 061 (15.8%) had two separation orders, 1 359 (2.4%) had three separation orders, 163 (0.3%) had four separation orders and 20 had five separation orders—which was the maximum number of separation orders per person.

Fig 1. Distribution of 24 433 COVID-19 isolation orders (in red) and 45 335 quarantine orders (in blue) over time in Berlin-Reinickendorf, Germany from March 2020 until December 2021.

Fig 1

Recommendation period for contact person definition: C1 = 03 March 2020 to 30 March 2021, C2 = 31 March 2021 to 19 May 2021, C3 = 20 May 2021 to 18 December 2021. The distribution of isolation and quarantine orders over time shows the COVID-19 waves.

Table 2. Analysis of 24 433 COVID-19 isolation and 45 335 quarantine orders by age and by period of contact person definition in Berlin-Reinickendorf, Germany from March 2020 to December 2021.
N ni nq d˜i d˜q ndi-pi ndq-pi ncc ncc (%) nncc nncc (%) nncc/ni ni/nq
total 266123 24433 45335 10.2 8.3 0.9 1.4 3484 7.7% 535 1.2% 0.02 0.54
0—6 18084 1383 9149 11.2 8.2 0.9 4.1 434 4.7% 97 1.1% 0.07 0.15
7—17 27001 3983 17528 11.1 7.9 1.6 5.2 867 4.9% 194 1.1% 0.05 0.23
18—64 158199 16041 16678 10.1 8.7 1 0.9 1838 11% 210 1.3% 0.01 0.96
65—110 62839 3026 1980 9.4 8.4 0.5 0.3 345 17.4% 34 1.7% 0.01 1.5
C1 266123 10876 29973 8.3 8.9 0.3 1 1802 6% 205 0.7% 0.02 0.36
C2 266123 2446 4791 11.4 9.5 0.1 0.2 658 14% 52 1.1% 0.02 0.51
C3 266123 11111 10571 11.8 5.9 0.5 0.2 1024 10% 278 2.6% 0.03 1.05
N ni nq d˜i d˜q ndi-pi ndq-pi ncc ncc (%) nncc nncc (%) nncc/ni ni/nq
total 266123 24433 45335 10.2 8.3 0.9 1.4 3484 7.7% 535 1.2% 0.02 0.54
0—6 18084 1383 9149 11.2 8.2 0.9 4.1 434 4.7% 97 1.1% 0.07 0.15
7—17 27001 3983 17528 11.1 7.9 1.6 5.2 867 4.9% 194 1.1% 0.05 0.23
18—64 158199 16041 16678 10.1 8.7 1 0.9 1838 11% 210 1.3% 0.01 0.96
65—110 62839 3026 1980 9.4 8.4 0.5 0.3 345 17.4% 34 1.7% 0.01 1.5
C1 266123 10876 29973 8.3 8.9 0.3 1 1802 6% 205 0.7% 0.02 0.36
C2 266123 2446 4791 11.4 9.5 0.1 0.2 658 14% 52 1.1% 0.02 0.51
C3 266123 11111 10571 11.8 5.9 0.5 0.2 1024 10% 278 2.6% 0.03 1.05

N = number of inhabitants of Berlin-Reinickendorf in the specific group, ni = number of isolation orders, nq = number of quarantine orders, d˜i = mean duration of isolation orders, d˜q = mean duration of quarantine orders, ndi-pi = number of days in isolation per inhabitant, ndq-pi = number of days in quarantine per inhabitant, ncc = contained cases, quarantines that had a directly following isolation period, ncc (%) = ncc in percent of all quarantine orders, nncc = non-contained cases, quarantine periods that had a following isolation period during day 1–7 after the quarantine period nncc (%) = nncc in percent of all quarantine orders. C1–3 = period of contact person definition

Analysis of the duration of isolation and quarantines

Overall, the public health agency ordered 684 years of isolation and 1 031 years of quarantine or 1 714 years separation in total. The median duration for isolation orders was di = 10 days (interquartile range 8—13). The duration changed between different periods of recommendations: the median of the duration during the recommendation periods were: 14 days for I1, 8 days for I2 and 12 days for I3. The overall median duration for quarantines was dq = 8 days (interquartile range 6—11). The median duration differed between periods of different recommendations and age groups: the median of the duration during the recommendation periods were 9 days for Q1, 9 days for Q2, 10 days for Q3 and 4 days for Q4. See Fig 2 for the distribution of age groups and recommended duration periods.

Fig 2. Duration of isolation and quarantine orders by age group and recommendation period for COVID-19 between 3 March 2020 and 18 December 2021 in Berlin-Reinickendorf.

Fig 2

The recommended period of separation Q1 from 3 March 2020 to 30 November 2020 was 14 days, in period Q2 from 1 December 2020 to 15 February 2021 also 14 days, but allowed for testing at day 10, in period Q3 from 16 February 2021 to 8 September 2021 again 14 days, in period Q4 from 9 September 2021 to 18 December 2021 10 days, but allowed for testing at day 5 (children) or 7 (adults). The recommended period I1 from 3 March 2020 to 1 July 2020 was 14 days, in period I2 from 2 July 2020 to 30 March 2021 10 days, in period I3 from 31 March 2021 to 18 December 2021 again 14 days.

Analysis of the ratio of contact persons per case

In the time period after the 24 May 2020 (the first date, when contact persons were recorded in the software), the overall ratio of contact persons was rqi = 1.89. (2.88 in the contact person definition period no. 1, 1.96 in period no. 2 and 0.95 in period no. 3).

Analysis of isolation orders following quarantine orders

In the time period after the 24 May 2020, 3 483 of 45 272 quarantine orders had a directly following isolation order (contained case) and 535 had a following isolation order during the 1 to 7 days after the quarantine order (non-contained case). The 3483 contained cases represent 14% of the 24433 isolation orders. There was a difference between the different periods of recommendations see Fig 3. During the recommendation periods for the duration of quarantine Q1–3, the percentage of non-contained cases was 1%; in Q4 the percentage of non-contained cases was 3%.

Fig 3. Analysis of isolation orders following quarantine orders and vice versa.

Fig 3

Isolation orders that were preceded by a quarantine order in percent of all isolation orders and quarantine orders that were followed by an isolation order in percent of all quarantine orders. Analysis by age group and recommendation period of contact person definition (C1 = 03 March 2020 to 30 March 2021, C2 = 31 March 2021 to 19 May 2021, C3 = 20 May 2021 to 18 December 2021.) between March 2020 and December 2021 in Berlin-Reinickendorf, Germany.

Analysis of timeliness

There were two periods in which a duration of 14 days of quarantine was recommended (Q1 and Q3). During these periods, our approximation of the median time period between the last contact and the beginning of the quarantine order was ddelay = 4 (interquartile range 1—6). The mean was 4.3 and 4 days for Q1 and Q3, respectively.

Discussion

Our analysis of the approximately 45 000 contact persons and 25 000 COVID-19 cases in Berlin-Reinickendorf quantifies the burden of isolation and quarantine orders for individuals infected with or exposed to COVID-19 with a total of 0.9 days of isolation and 1.4 days of quarantine per inhabitant. We showed that children were affected by quarantine orders to a larger extent than adults and that the local public health agency adapted the way of ordering separations when the Robert Koch Institute changed their recommendations. Our study found 3484 contained cases—15% of the total number of cases.

Differences between children, adults and senior citizens

The local public health agency issued more quarantine orders per 100 inhabitants for children than for adults under 65 or for senior citizens. The same can be observed for isolation orders, but to a lesser degree, see Table 2. The Number of days in quarantine per inhabitant was roughly 20 times higher for school children than for senior citizens. The differences between the age groups can also be observed during different periods of recommendation. The higher number of isolation orders reflects the incidence of the age groups [27]. Our finding of the higher quarantine numbers could be due to the fact that children have more contacts than adults and even more than senior citizens (assortative contact patterns) [22]. Persons with a higher number of contacts have a higher probability of being a contact person of a COVID-19 case. Thus, our differences in age groups might reflect only the higher number of contacts among children. Apart from a legitimate difference in quarantine orders per 100 inhabitants based on assortative contact patterns, our finding could also be due to the workflow of the agency. The local public health agency needs to know about the contact and their address to order a quarantine. These preconditions are much more likely to be met amongst school and kindergarten children. It is easier to identify a child as a contact person than an adult. This would reinforce the feeling that children had to bear an unjustly high burden of the intervention, as it has been expressed widely throughout the media [28].

Comparison of isolation and quarantine orders with school closures

Several studies, including large reviews, found that school closures reduce the transmission of the disease [2931]. In the setting of Germany, Erhard et al. did not identify a significant increase of transmission after school openings in the state of Baden-Württemberg [32], whereas Sorg et al. calculated a decrease of 24% of expected cases during lockdown restrictions in Germany [33]. Compared to school closures, the intervention of isolation and quarantine orders was less costly in terms of school days lost. In Berlin, schools were closed for 124 days (from 13 March 2020 to 29 May 2020 and from 06 January 2021 to 22 February 2021). In this study, we found that the local public health agency ordered 6.8 days of separation order per schoolchild, which would be 1/18 of the number of school days lost from school closures. However, for the individual affected by isolation and quarantine the individual separation order is probably perceived as a harsher measurement than school closure, because a school closure does not confine a person to their apartment. For future pandemics, decision makers have to carefully weigh the costs and benefits in terms of lost school and working days for each intervention.

Average number of contact persons

Overall, the local public health agency identified less than two contacts per case. This is comparable with studies from the United States of America. Koetter et al. describes a student imitative that found 953 contacts for 536 cases which results in 1.8 contacts per case. Sachdev et al identified 0.7 contacts per case in the San Francisco Area. Shi et al. found 10.8 contacts per COVID-19 cases in China [17]. During the first outbreak in Germany 241 contacts from 17 cases were identified [34]. The mean number of contacts found in this study is much lower than the usual mean number of contacts per day (not contacts of COVID-19 cases) that Mossong et al. reported (7.95 mean contacts for Germany) [22]. The discrepancy between the usual number of contacts and the mean number of contacts found by us is even greater when it is taken into account that the contact definition used by the local health department includes aerosol contact, which would increase the average number of contacts compared to the study by Mossong et al. who studied face-to-face and skin-contact. During the pandemic, the contact monitor of the COVID-19 mobility project analysed telephone data and found 12.2 mean contacts per person (again not contacts of COVID-19 cases) and a decrease of the number of contacts at the beginning of the pandemic [35]. Our comparably low number of mean contacts can be considered to be a desired direct effect of the recommendation by the authorities to cut down contacts. But the identification of contacts is highly dependent on the workload of the agency and the rigour of contact tracing. So our low number of mean contacts per COVID-19 case could also indicate that not all contacts could be identified by the local public health agency or that cases were reluctant to give information about contacts.

Effect of the contact tracing on the transmission of COVID-19

Contact tracing, which includes some sort of quarantine orders, has been implemented by 183 of 187 countries as measured by the Oxford COVID-19 Government Response Tracker [36]. It is considered to be one of the cornerstones of the response [37] and is also recommended by the WHO [1]. Pozo-Martin et al. found that there is evidence regarding the incremental effectiveness of both manual and digital contact tracing for COVID-19 epidemic control [38].

Isolation orders of infectious individuals and quarantine orders of contacts decrease the disease burden for the population, which has been shown in an epidemiological model by Agusto et al [39]. Nussbaumer-Streit et al. found a strong influence of quarantine (alone or in combination with isolation) on the reproductive number in a rapid review including 29 studies for the WHO [2]. On the other hand, empirical studies that compared several non-pharmaceutical interventions did not find an effect of quarantine on the spread of disease [29, 30]. The work of the local public health agency resulted in 3484 contained cases who were taken out of the transmission chain (persons that had an isolation period directly following a quarantine). We likely underestimated the number of contained cases, as our records included contact persons but not cases residing outside Berlin-Reinickendorf. Unlike contact persons, cases outside Berlin-Reinickendorf were managed by their respective local agencies, leading to potential underrepresentation in our data. Some of the contained cases might have spread the disease before they were ordered to quarantine (see the paragraph on timeliness) or during their quarantine order, because they did not adhere to the intervention.

Influence of contact person definition

Our data show that during times with a sensitive contact person definition (Contact person definition period C1) the mean number of contacts per COVID-19 case was higher than during times with a less sensitive contact person definition (Contact person definition period C2–3). Consequently, during times with a sensitive definition, the percentage of contained cases was lower and the number of cases that were previously identified as contact persons was higher. This is consistent across all age groups as illustrated in Fig 3. It seems plausible that a change in the recommended definition results in a different number of identified contact persons, however our evidence must be considered as weak, see limitation section. The right balance between specificity and sensitivity for the contact person definition depends on the strategy of the government.

Effect of the recommendations of the Robert Koch Institute on duration of isolation and quarantine orders

The results show that the duration of isolation and quarantine orders changes along with the recommended period, which indicates that the local public health agency adhered to the recommendations by the Robert Koch Institute. Fig 2 shows a clear pattern of the duration that correlates with the recommendations as given in Table 1. This result indicates that the recommendations caused the change in duration of isolation and quarantine orders.

Timeliness of contact tracing

The calculated median duration of quarantine orders was lower than the recommended time by the Robert Koch Institute which is due to the fact that there is a delay between the date of contact and the identification and subsequent quarantine order by the local public health agency. The following steps take place between the contact to the index case and the quarantine order: The index case conducts a test, the test result is reported and processed, the agency reaches out to the index case to identify the contact persons and contacts them. The median delay of approximately 4 days in contact tracing, as identified in our study, represents a shortcoming in the containment efforts for COVID-19. Prompt detection of contact persons is crucial to effectively prevent the transmission of the virus [40].

Effect of the duration of quarantines on the number of contained cases

During the course of the pandemic, the recommended time period for the isolation and quarantine period was changed several times. A reduction in the duration of quarantine increases the risk of having non contained cases (contact persons that turned into cases not directly but one to seven days after their quarantine order). Chinese authors suggest a quarantine duration for longer than 14 days—which was the maximum in Germany—based on a calculated 9% of total cases that had symptoms or other events beyond 14 days [41]. In Europe, Ashcroft et al. suggested that a reduction of the quarantine period from 10 to 7 days combined with testing strategies can be a feasible method to reduce the burden of quarantine for contacts and returning travellers [42]. The recommendations of the Robert Koch Institute on the duration of quarantine (Q4) proposed a reduction of the quarantine duration similar to what Ashcroft et al. suggested—the main exception being a possibility for children to end the quarantine after 5 days with a negative test. Comparing the time period for quarantine duration before and after this change (Q1–3 vs. Q4), we found an increase in the number of non contained cases from 1% to 3%. For the measurement of this analysis our data is limited—see limitation section.

Limitations of this work

Our data has several limitations. Firstly, the primary aim of the local public health agency is not to acquire data for for scientific purposes but to prevent the spread of the disease. Thus, data was not collected with the scientific scrutiny. Secondly, the data correctness depends on the number and experience of the staff. The staff had a high turnover during the pandemic and the workload changed several times during the pandemic. Other factors, however, favour the correctness of data collection: the local public health agency is required by law to do contact tracing [43], persons usually need a document stating that they are placed in isolation or quarantine—to generate this document the isolation or quarantine order needs to be entered into the reporting software. We made efforts to minimise the error due to work overload by reducing our analysis to the time period without excessive work overload. Thirdly, there are severe limitations in the time dependent analysis, e.g., the evaluation of the effect of different recommendations, since we are not able to disentangle the different effects on our measured variables due to the many number of parameters that changed during the course of the pandemic. Besides the different recommendations on isolation and quarantine duration and the definition of contact persons, confounding variables include: vaccination status, variants of the virus, work load, number of staff, experience of staff, different contact pattern of cases, testing behaviour, contact person behaviour. Fourth, for the analysis that involved a comparison of isolation and quarantine orders, we could not directly link a case to a contact person (thus we could not calculate secondary attack rates by type of contact or other useful measures like direct number of contacts per person). Fifth, contact persons that turned into a case were sent to another local public health agency if they resided outside of Berlin-Reinickendorf. A sixth limitation is that our data reflects only the direct work of the local public health agency and cannot measure the indirect effects: inhabitants of Berlin-Reinickendorf may have been isolating or quarantining themselves or on the basis of the law of the federal state or the district decree without giving a notification to the local public health agency. Seventh, the true number of cases is not known and so impact of the public health agency is underestimated.

Conclusion

Isolation of COVID-19 infected individuals and quarantine of contacts is one important tool to slow down the pandemic. However, separation orders cause health hazards, such as mental health impacts. Our study concludes the following for Berlin-Reinickendorf: the local public health agency ordered 1.4 days of quarantine and 0.9 days of isolation per inhabitant. The local public health agency contained 3484 cases. Contact tracing places a burden on the population, but the number of days lost due to isolation or quarantine are much fewer than the days lost to school closures or work closures. The local public health agency found 1.9 contacts per case—clearly lower than Chinese agencies or the investigations during the first outbreak in Germany or the usual mean number of contacts (in the absence of COVID-19). This indicates that the agency was not able to provide rigorous contact tracing. Children were quarantined to a much higher degree than adults or senior citizens. Our data indicate that the recommendations by the Robert Koch Institute had an influence on the work of the local public health agency. With limitations, we found a delay of 4 days between the date of contact and the date the contact person was ordered to quarantine.

Supporting information

S1 Table. Detailed table of time periods of relevant recommendations of the Robert Koch Institute for isolation duration, quarantine duration and contact person definition.

(PDF)

pone.0271848.s001.pdf (67.5KB, pdf)
S1 Fig. Exclusion of data entries.

(PDF)

pone.0271848.s002.pdf (22.9KB, pdf)

Acknowledgments

We thank Patrick Larscheid for his organisational support and the staff of the local public health agency for their work in protecting the people of Berlin-Reinickendorf. Many thanks to Maria Helmrich for her help with the wording.

Data Availability

All code and data-files are available from the github repository https://github.com/jakobschumacher/quarantine-isolation-analysis.

Funding Statement

Jakob Schumacher received no specific funding for this work. Lisa Kühne, Sophia Brüssermann, Benjamin Geisler and Sonja Jäckle were funded by the German Federal Ministry of Education and Research (BMBF, Project EsteR, Funding Code: 13GW0542).

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Decision Letter 0

Srikanth Umakanthan

19 Aug 2022

PONE-D-22-19240COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?PLOS ONE

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1. Introduction on COVID-19 with emphasis on its origin and transmission (refer and cite: doi: 10.1136/postgradmedj-2020-138234).

2. Include the role of vaccination (refer and cite: doi: 10.3390/vaccines91010640

3. Include the role of protective medications in individuals with high risk of COVID-19 (refer and cite: doi: 10.1186/s41231-021-00102-4).

4. Include a comparison of support programs in Germany with that of other regions (refer and cite: doi: 10.3389/fpubh.2022.844333)

5. Role of predictors for vaccine hesitancy in Germany. (refer and cite: doi: 10.1136/postgradmedj-2021-141365.

6. where there any inclusion and exclusion criteria among the selected populations?

7. Where there any missing records? Kindly mention in your methodology.

8. Mention if any limitations were identified in your study and also mention the follow up steps for further analysis.

Reviewer #2: Well written manuscript and I endorse it for publication. The authors have well versed the materials, methods and statistical analysis. The results are well described and illustrated in the figures and tables.

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PLoS One. 2024 Mar 11;19(3):e0271848. doi: 10.1371/journal.pone.0271848.r002

Author response to Decision Letter 0


2 Nov 2022

Dear ladies and gentlemen,

thank you for your review of the manuscript. Please find our changes in the manuscript. I hope that I corrected all you points and got the latex and naming conventions right.

Best regards

Jakob Schumacher and the coauthors

Points raised by Reviewer No. 1

1. Introduction on COVID-19 with emphasis on its origin and transmission (refer and cite: doi: 10.1136/postgradmedj-2020-138234).

2. Include the role of vaccination (refer and cite: doi: 10.3390/vaccines91010640)

3. Include the role of protective medications in individuals with high risk of COVID-19 (refer and cite: doi: 10.1186/s41231-021-00102-4).

4. Include a comparison of support programs in Germany with that of other regions (refer and cite: doi: 10.3389/fpubh.2022.844333)

5. Role of predictors for vaccine hesitancy in Germany. (refer and cite: doi:10.1136/postgradmedj-2021-141365.

6. where there any inclusion and exclusion criteria among the selected populations?

7. Where there any missing records? Kindly mention in your methodology.

8. Mention if any limitations were identified in your study and also mention the follow up steps for further analysis.

Answers to Reviewer No. 1

Thank you for your contributions, please find our responses to your points beneath

Answer to point 1-3 and 5

We included a short introduction to COVID-19 including its origin, pathogenesis and transmission

as well as the role of vaccination, vaccine hesitancy and protective medications. We tried to keep it

short to not waste the time of the reader. Please see the revised manuscript.

1. Holmes EC, Goldstein SA, Rasmussen AL, Robertson DL, Crits-Christoph A, Wertheim JO,

et al. The origins of SARS-CoV-2: A critical review. Cell. 2021;184(19):4848–4856.

doi:10.1016/j.cell.2021.08.017.

2. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nature

Reviews Microbiology. 2021;19(3):141–154. doi:10.1038/s41579-020-00459-7.

3. Fiolet T, Kherabi Y, MacDonald CJ, Ghosn J, Peiffer-Smadja N. Comparing COVID-19

vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants

of concern: a narrative review. Clinical Microbiology and Infection. 2022;28(2):202–221.

doi:10.1016/j.cmi.2021.10.005.

4. Pires C., Global Predictors of COVID-19 Vaccine Hesitancy: A Systematic Review. Vaccines.

2022;10(8):1349. doi:10.3390/vaccines10081349.

Answer to point 4

Support programs are an important part in the response to COIVD-19. We feel that the

comparison of support programs with different regions would merit its own publication. We decided

to not include such a comparison to not extend the scope of our publication.

Answer to point 6 and point 7

Thank you for your point. We have not been clear enough in displaying our population, which we

addressed in our revised manuscript. In our opinion we have already addressed inclusion and

exclusion criteria as well as our handling of missings by stating that we took all the entries in our

database (from the study period) on separation orders. Then we described which of those orders we

took (all with a valid person ID with no missing data in the variables ”separation from” and

”separation until”. We then proceeded to remove all entries that we regarded as a typing error and

then combining overlapping order double entries of separation orders. However we might not have

been clear enough in our description so we addressed that point to make it more understandable.

Answer to point 8

Agreed, limitations are an important part in every publication. We have identified five limitations

that we feel important: 1) Aim of data collection, 2) Overload of work that alters data collection 3)

changes over time 4) No direct linking of cases and their contact persons and 5) indirect effects. We

also wrote what we think limits the influence of these limitations. We included a paragraph on

those five limitations. Also when we feel that on of our conclusions had a limitation that addressed

it directly we tried to make that clear directly beside that point. We revised the section on

limitations to make it more understandable and to better show their importance.

Points raised by Reviewer No. 2

The authors have well versed the materials, methods and statistical analysis. The results are well described and illustrated in the figures and tables. We included the following additional citations

Answers to Reviewer No. 2

Thank you for you positive feedback

Attachment

Submitted filename: rebuttal_letter.pdf

pone.0271848.s003.pdf (74.6KB, pdf)

Decision Letter 1

Srikanth Umakanthan

6 Jan 2023

PONE-D-22-19240R1COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?PLOS ONE

Dear Dr. Jakob,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Academic Editor

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PLoS One. 2024 Mar 11;19(3):e0271848. doi: 10.1371/journal.pone.0271848.r004

Author response to Decision Letter 1


24 Feb 2023

Please find the latest E-Mail regarding the Reviewprocess with the latest E-Mail being:

Dear Dr. Schumacher,

Apologies for the delay in getting back to you. I've consulted with our internal team and want to let you know that you do not need to cite the papers requested by Reviewer 1. You are welcome to resubmit your manuscript at any time.

We will follow up internally regarding your concerns about this review. If you have any further questions, please feel free to reach out.

Kind regards,

Sabine Henderson

Attachment

Submitted filename: rebuttal_letter.pdf

pone.0271848.s004.pdf (74.6KB, pdf)

Decision Letter 2

Emanuele Crisostomi

5 Dec 2023

PONE-D-22-19240R2COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?PLOS ONE

Dear Dr. Schumacher,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 19 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Emanuele Crisostomi, PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

This Academic Editor received the assignment of this manuscript only three weeks ago, and realized that the manuscript had a past long history with unsuccessful attempts to finding appropriate reviewers, since the original ones were not available for a second round of reviews.

The new reviews are overall positive, and a minor review is recommended. In particular, one Reviewer provides a number of punctual constructive comments for improving the manuscript.

The next round of reviews will be faster and a final decision will be taken.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

Reviewer #5: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Partly

Reviewer #4: Yes

Reviewer #5: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: (No Response)

Reviewer #4: Yes

Reviewer #5: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Overall this is an interesting account of the work of a health department during the COVID-19 pandemic, including counts of isolation and quarantine orders as well as intervals e.g. between contact and beginning of quarantine. A few amendments might make the paper more informative. Reading the manuscript by a native speaker may be advisable.

Abstract:

-The intro could be strengthened (the harm infliction is not a great part of the paper, is it?), and please add what the aim of the paper is.

-not sure if the analysis on the “dependence on the recommendations by the Robert Koch Institute” is that informative for the readers, I suggest to de-emphasize this part throughout.

-“delay of 4 days between contact and quarantine order”: what is meant: “last contact”? what did you do with family members as there was no point contact, but usually continuous contact? (perhaps address in Methods (were they excluded for that purpose?))

-“3484 of contacts were in quarantine…”: relate to the number of cases (1/18) and to the number of quarantines, and eliminate the word “of”. If you are able to quantify the number of human resources (man-hours or something like that) you could relate to that measure, too.

-I suggest to add here the proportion of the population that received at least one isolation or quarantine order, for simplicity sake you could assume that all isolation and quarantine orders were different persons

-the claim that fewer days were lost due to isolation or quarantine orders is not quantified.

-I would change the conclusions. (1)the part with the Robert KochInstitute I would leave out, (2)the conclusion that the mean number of contacts is less than expected comes out of the blue as you have not said what you expected. For example: you could say that a substantial proportion of the population had been separated, that the efforts saved the children from school closures, and that a substantial number of cases occurred when in quarantine.

Methods

-perhaps start with how you did the routine work and the contact tracing, how you monitored quarantined persons if they became a case (self monitoring / health department monitoring, symptom monitoring, mandatory testing?, …)

-line 73: what was the unit of observation in that database? an order for isolation, or an order to quarantine? either?

-what you could do and would be quite cool is to quantify the cases by the day they were removed from the public, e.g. x1 number of cases on day -2 before symptom onset (because they were in quarantine), x2 number of cases from day -1 before symptom onset, x3 number of cases on the day when they had symptom onset, etc. I think that should be feasible and would be quite good information for modelers.

-paragraph on “Number of quarantine orders…”: please give examples. Line 130: “other cases”: not clear what is meant here.

-please explain here how you dealt with household contacts from the point of view “last contact”. Did you exclude household contacts because they usually had no fixed, identifiable single contact?

Results

-Line 149: there are two “??”, please complete manuscript

-Fig.1: Since this is a paper that gives detailed account of the efforts of a health department I suggest to overlay the number of persons that were involved with contact tracing (by week or month, if possible) to show the amount of work and resources that has gone into this effort.

- can you give also the number of cases reported, please?, perhaps also in Table 2 and/or Fig.1

- please describe / point out the most important things in the figure/table (don’t leave the reader alone with it)

- Table 2, footnotes: add what N means

-Line 192: the number of contacts per case is quite small. given that these include also cases in schools with likely substantially more contacts it suggests that mainly the household contacts were traced. Please add in the Limitations that this low number of contacts traced may be a reason that the percentage of contained cases of all isolation orders is not more than 14%. At any rate: could you please give a break-down of the type of contacts, e.g. household, work, school, other, or something like that? In fact, I would consider restricting the analysis of contacts to household contacts as I assume that the vast majority of contacts are household contacts. This would strengthen the paper.

- could you add in the table the ratio of contained cases per quarantined persons (ncc/nq) or ni/nq (isolations per quarantined persons)

- I think the ratio of isolations in the 1-7 days after end of quarantine : isolations during quarantine is a useful measure that should be provided.

- Lines 199/200: what do you mean by “non-contained cases”? please give raw numbers here, too.

-perhaps provide also the percentage of the population with isolation order or quarantine order?

Discussion

-Limitations are usually at the end of the paper unless the editors wish something else

-I think another limitation is that there are also cases that were never known to the health department, which is of course not the fault of the health department, however, since you do not know the true number of cases (including those never diagnosed who still contribute to transmission) you underestimate the impact of the health department

-Line 232: does that mean you could not calculate secondary attack rates, e.g. by type of contact (household, work, etc.) or age of contact, or an average number of cases by source case (e.g. to identify super-spreaders)?

-Line 240: I cannot extract that or at least not easily from Table 2, please be more precise?

-Line 283: … or a reluctance of cases to give information about contacts

-Line 295: an update has been published, however, a lot of the evidence stems from SARS and MERS; there is other publications with a focus on C-19, such as Pozo-Martin (EJE, 2023, "Comparative effectiveness..."), Craig (JMIR 2021, "Effectiveness of contact tracing...") and Fetzer (PNAS, 2021, "Measuring the scientific effectiveness...")

-Line 299: I dont understand what is meant here

-Line 327: “The rough estimate for the median delay of 4 days that we found must be considered as a flaw in the contact tracing. For COVID-19, an early detection of contact persons is key to hinder transmission of the disease” – please check English (particularly “flaw” and “hinder” ??)

-but did adherence increase and/or administrative feasibility improve?

-Line 357: for modellers that is good information. however, again, most informative would be the proportion of cases that were isolated by day in relation to symptom onset (see above).

- The authors calculated the number of contacts per case. I think it would be more instructive to stratify by those cases who were not previously in the system as contact person and those who were. The latter will likely have very few contacts, the first might have a number of contacts. In addition it would be nice to stratify by age (of the case; very broadly, say <18 and 18+ year old), because children should have quite a bit more contacts than adults.

Reviewer #4: This is a nicely conducted and well-written paper that provides detailed descriptives on the COVID-19 isolation and quarantine orders by age groups and time periods in the Berlin-Reinickendorf area in Germany. Overall, I think the manuscript is well-structured and the analyses are appropriate in answering the research questions. The authors have also responded to the previous review comments sufficiently.

I only have few minor comments for consideration before publication:

- It will help the readers understand the context better if the authors can also state in the Abstract the total number of individuals analyzed.

- In Table 2, it will be helpful to mark the percentages as “%”, and provide SD for mean values. The abbreviations are also a bit hard to understand at first glance (for example it is not intuitive to me how “ncc” refers to “quarantines that had a directly following isolation period”). As these abbreviations are used only once in Table 2, the authors can consider write them out in words or improve the labels, if possible.

- It is generally recommended to avoid using the term “elderly”. I suggest changing it to “older adults”, “older persons”, or similar throughout the manuscript.

Reviewer #5: This is an intriguing study that provides valuable insights into policies regarding isolation and quarantine for COVID-19. The methodology is robust, and the contents are well-written. The results not only capture a specific time during the COVID-19 era but also offer potential implications for future pandemics or emerging diseases. I have only a few minor comments:

1. I noticed that reference 21 was not cited in the manuscript. Additionally, please renumber the references in the order they appear in the manuscript. As an example, references 36-38 currently appear in the first paragraph of the Introduction, which requires revision for proper numbering.

2. Line 11-12: "Vaccines have been developed and proven successful in preventing severe disease and death [40], ...." → I suggest change this sentence to "Vaccines have been developed and proven successful in inducing seroconversion (cite the following reference 1), preventing severe disease and death [40], ...."

Reference:

[1] Safety and Seroconversion of Immunotherapies against SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis of Clinical Trials. Pathogens. 2021 Nov 24;10(12):1537. doi: 10.3390/pathogens10121537. PMID: 34959492; PMCID: PMC8706687.

3. Line 51-52: "Jian et al. reported on the Taiwanese digital system TRACE analysing 487 cases and 8051 contact persons [12]." → To emphasize the public health implications of these particular systems, I suggest change this sentence to: "Jian et al. reported on the Taiwanese digital system TRACE, analyzing 487 cases and 8051 contact persons [12]. Public health implications of these systems included surveillance of travel history (cite the following reference 1) and ensuring an adequate quantity of personal protective equipment (cite the following reference 2)."

References:

[1] Integrating travel history via big data analytics under universal healthcare framework for disease control and prevention in the COVID-19 pandemic. J Clin Epidemiol. 2021 Feb;130:147-148. doi: 10.1016/j.jclinepi.2020.08.016

[2] Big Data-driven personal protective equipment stockpiling framework under Universal Healthcare for Disease Control and Prevention in the COVID-19 Era. Int J Surg. 2020 Jul;79:290-291. doi: 10.1016/j.ijsu.2020.05.091

I look forward to reviewing a revised version of this work based on my feedback!

**********

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Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

**********

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PLoS One. 2024 Mar 11;19(3):e0271848. doi: 10.1371/journal.pone.0271848.r006

Author response to Decision Letter 2


21 Dec 2023

Points raised by Reviewer No. 3

======================

Thank you for your thorough feedback and the time you spend on improving the

paper.

1. The intro could be strengthened (the harm infliction is not a great part of the paper, is it?),

and please add what the aim of the paper is.

The introduction aims to provide a comprehensive overview, including potential

negative impacts of isolation and quarantine measures. The publication is not

about what adverse effects are done by quarantine and isolation but to measure

the quantity of isolations and quarantines. In my eyes the aim is quite cleary

covered with: The goal of this work is to quantify and analyse isolation and

quarantine orders from a local public health agency in Germany to assess

differences among age groups, mean number of contacts, timeliness of quarantine

orders, the number of contained or non-contained cases and to estimate the

impact of the contact person tracing. I updated the intro to improve the part

about the adverse effects.

2. not sure if the analysis on the “dependence on the recommendations by the Robert Koch

Institute” is that informative for the readers, I suggest to deemphasize this part throughout.

Thank you for your input regarding the analysis on the dependence on the

Robert Koch Institute’s recommendations. I believe this aspect is crucial as it

highlights the significance of these recommendations in guiding public health

responses. I think it is important to know for future pandemics if local agencies

follow or dont follow national recommendations. This analysis reflects the impact

of these guidelines and shows that the national institute plays a key role.

Therefore, I suggest not to deemphasize this part.

3. “delay of 4 days between contact and quarantine order”: what is meant: “last contact”? what

did you do with family members as there was no point contact, but usually continuous

contact? (perhaps address in Methods (were they excluded for that purpose?))

Thank you for your point regarding the ’delay of 4 days between contact and

quarantine order’ and the definition of ’last contact’, especially in the context of

family members. To clarify, I have added a paragraph in the Methods section

explaining ’last contact’ in the paragraph explaining the timeliness.

4. “3484 of contacts were in quarantine. . . ”: relate to the number of cases (1/18) and to the

number of quarantines, and eliminate the word “of”. If you are able to quantify the number of

human resources (man-hours or something like that) you could relate to that measure, too.

Point taken. I changed the sentence in the introduction to relate to the number

of cases and quarantines. Unfortunately we were not able to quantify the number

of human resources, although I agree that this would be a valuable addition

5. I suggest to add here the proportion of the population that received at least one isolation or

quarantine order, for simplicity sake you could assume that all isolation and quarantine orders

were different persons

Thank you for your point. I added the proportion of the population as you

suggested.

6. the claim that fewer days were lost due to isolation or quarantine orders is not quantified.

I would argue that I did quantify this aspect with the sentence in the discussion:

Compared to school closures, the intervention of isolation and quarantine orders

was less costly in terms of school days lost. In Berlin, schools were closed for

124 days (from 13 March 2020 to 29 May 2020 and from 06 January 2021 to 22

February 2021). In this study, we found that the local public health agency

ordered 6.8 days of separation order per schoolchild, which would be 1/18 of the

number of school days lost from school closures. To clarify I moved bits of this

into the introduction, which is probably the better position for this sentence.

7. I would change the conclusions. (1)the part with the Robert KochInstitute I would leave out,

(2)the conclusion that the mean number of contacts is less than expected comes out of the

blue as you have not said what you expected. For example: you could say that a substantial

proportion of the population had been separated, that the efforts saved the children from

school closures, and that a substantial number of cases occurred when in quarantine.

As stated above I think the part with the recommendations of the RKI is

important, so I would suggest to leave it in. In the paper we compared our

findings to the literature that calculates around 8 contacts per day. I updated the

abstract and the introduction to better clarify that point. I included your

suggestions for further conclusions.

8. Methods: perhaps start with how you did the routine work and the contact tracing, how you

monitored quarantined persons if they became a case (self monitoring / health department

monitoring, symptom monitoring, mandatory testing?, . . . )

Agreed, this information is missing. I added a paragraph that includes this.

9. line 73: what was the unit of observation in that database? an order for isolation, or an order

to quarantine? either?

That was indeed unclear. I clarified that I meant both.

10. what you could do and would be quite cool is to quantify the cases by the day they were

removed from the public, e.g. x1 number of cases on day -2 before symptom onset (because

they were in quarantine), x2 number of cases from day -1 before symptom onset, x3 number

of cases on the day when they had symptom onset, etc. I think that should be feasible and

would be quite good information for modelers.

Thank you for your interesting suggestion. While this approach should indeed

offer valuable insights for epidemiological modelling the information on the onset

of disease is not available in the current data.

11. paragraph on “Number of quarantine orders. . . ”: please give examples. Line 130: “other

cases”: not clear what is meant here.

I have revised the paragraph with the aim of enhancing its readability.

12. please explain here how you dealt with household contacts from the point of view “last

contact”. Did you exclude household contacts because they usually had no fixed, identifiable

single contact?

Thank you for your point. I added a sentence to explain our management in

household situations

13. Line 149: there are two “??”, please complete manuscript

There was a latex-problem that is hopefully solved now

14. Fig.1: Since this is a paper that gives detailed account of the efforts of a health department I

suggest to overlay the number of persons that were involved with contact tracing (by week or

month, if possible) to show the amount of work and resources that has gone into this effort.

That would indeed be great if we had the numbers on that. Unfortunately we did

not track the number of persons involved with contact tracing sufficiently

15. can you give also the number of cases reported, please?, perhaps also in Table 2 and or Fig 1

Added this missing information

16. please describe point out the most important things in the figure/table (don’t leave the reader

alone with it)

We previously had a discussion in the team whether to show this graph because it

does not directly lead to any conclusions. In the end we felt that it has merit to

give the reader a sense about the distribution of the cases and contacts over time.

I added a sentence to include this information.

17. Table 2, footnotes: add what N means

This was indeed missing

18. Line 192: the number of contacts per case is quite small. given that these include also cases in

schools with likely substantially more contacts it suggests that mainly the household contacts

were traced. Please add in the Limitations that this low number of contacts traced may be a

reason that the percentage of contained cases of all isolation orders is not more than 14%. At

any rate: could you please give a break-down of the type of contacts, e.g. household, work,

school, other, or something like that? In fact, I would consider restricting the analysis of

contacts to household contacts as I assume that the vast majority of contacts are household

contacts. This would strengthen the paper.

For me personally this is one of the most important findings of our study. We

expect to have usually around 8 contacts per person per day (Mossong et al.) and

for the contact definition we were looking for up to 14 days of potential contacts.

So we should have a lot more than 2 contacts per case. Although one could argue

that people cut down their contacts during the pandemic. Chinese papers

reported around 10 contacts per case which is maybe why they managed to

reduce the number of cases close to zero. So if we have another pandemic where

we want to follow a zero-strategy we should consider stepping up the search for

contacts. The other point - breaking down by type of contact - would be a

valuable addition. But this information was not recorded in the software. You

can see in the later parts of the publication the breakdown by age which gives an

indication for the difference between schools and household. Interestingly the

percentage of contained cases goes up if you have lower numbers of contacts per

case - probably because you get the most important contacts only. But the

absolute number of contained cases would rise the more contacts are found.

19. could you add in the table the ratio of contained cases per quarantined persons (ncc/nq) or

ni/nq (isolations per quarantined persons)

The ratio of contained cases per quarantined persons is already present as a

percentage in the colum ncc-p. I added the % symbol to make it clearer. I added

the ni/nq (isolations per quarantined persons).

20. I think the ratio of isolations in the 1-7 days after end of quarantine : isolations during

quarantine is a useful measure that should be provided.

I added the ratio in the column nncc/ni

21. Lines 199/200: what do you mean by “non-contained cases”? please give raw numbers here,

too.

What we mean with non-contained case is explained in the methods and in the

mentioned paragraph two sentences earlier. We wanted to avoid writing had a

following isolation order during the 1 to 7 days after the quarantine order several

time.

22. perhaps provide also the percentage of the population with isolation order or quarantine

order?

We have: The local public health agency ordered ni = 24 433 isolations and nq =

45 335 quarantines (ni-p100 = 9.2 isolation orders and nq-p100 = 17 quarantine

orders per 100 inhabitants). We hope that this gives adequate information.

Discussion

23. Limitations are usually at the end of the paper unless the editors wish something else

Thanks for the clarification: I moved it to the end

24. I think another limitation is that there are also cases that were never known to the health

department, which is of course not the fault of the health department, however, since you do

not know the true number of cases (including those never diagnosed who still contribute to

transmission) you underestimate the impact of the health department

I added the limitation.

25. Line 232: does that mean you could not calculate secondary attack rates, e.g. by type of

contact (household, work, etc.) or age of contact, or an average number of cases by source

case (e.g. to identify super-spreaders)?

Yes, we would have loved to calculate secondary attack rate by type of contact,

but that is not possible. Also not the other parameters. I have incorporated that

information into the text.

26. Line 240: I cannot extract that or at least not easily from Table 2, please be more precise?

I changed the sentence and included the calculations for the number: ”20 times”

higher in the result section under Analysis of quantity of isolation and

quarantine orders

27. Line 283: . . . or a reluctance of cases to give information about contacts

Thank you for the good addition.

28. Line 295: an update has been published, however, a lot of the evidence stems from SARS and

MERS; there is other publications with a focus on C-19, such as Pozo-Martin (EJE, 2023,

”Comparative effectiveness...”), Craig (JMIR 2021, ”Effectiveness of contact tracing...”) and

Fetzer (PNAS, 2021, ”Measuring the scientific effectiveness...”)

Thank you for the update. I included the Review bei Pozo-Martin.

29. Line 299: I dont understand what is meant here

I updated the sentence, and also the corresponding part in the limitation section.

30. Line 327: “The rough estimate for the median delay of 4 days that we found must be

considered as a flaw in the contact tracing. For COVID-19, an early detection of contact

persons is key to hinder transmission of the disease” – please check English (particularly

“flaw” and “hinder” ??)

Changed the two sentence - hopefully for the better

but did adherence increase and/or administrative feasibility improve?

Our study was not meant to measure adherence. We see that the number of non

contained cases goes up the shorter the quarantine period. For measuring

adherence we would needed to question cases and contacts after the order. I

would have loved to do that - also to see how the agency could have improved its

work. This would be something for another study.

32. Line 357: for modellers that is good information. however, again, most informative would be

the proportion of cases that were isolated by day in relation to symptom onset (see above).

I agree, but we dont have the symptom onset in our dataset.

33. The authors calculated the number of contacts per case. I think it would be more instructive

to stratify by those cases who were not previously in the system as contact person and those

who were. The latter will likely have very few contacts, the first might have a number of

contacts. In addition it would be nice to stratify by age (of the case; very broadly, say ¡18 and

18+ year old), because children should have quite a bit more contacts than adults.

You are perfectly right, this would be valuable information. But as stated in the

limitation section we cannot directly link a contact person to a case, because this

is information was not reliably stored in the software. We get a hint by the high

number of contact persons within the group of children, which is very likely due

to school.

Points raised by Reviewer No. 4

===============================================

Thank you for your valuable feedback

1. It will help the readers understand the context better if the authors can also state in the

Abstract the total number of individuals analyzed.

Agreed. Added the figure of the total population

2. In Table 2, it will be helpful to mark the percentages as “%”, and provide SD for mean values.

The abbreviations are also a bit hard to understand at first glance (for example it is not

intuitive to me how “ncc” refers to “quarantines that had a directly following isolation

period”). As these abbreviations are used only once in Table 2, the authors can consider write

them out in words or improve the labels, if possible.

Thanks for the feedback. I Added the % and explained that ”ncc” means

non-contained case, which was indeed not intuitive. The table is to wide to fit the

page. I dont feel that the sd for the mean values are more important than the

other given values.

3. It is generally recommended to avoid using the term “elderly”. I suggest changing it to “older

adults”, “older persons”, or similar throughout the manuscript.

Thanks for the correction. I changed it to senior citizens

Points raised by Reviewer No. 5

=================================

1. I noticed that reference 21 was not cited in the manuscript. Additionally, please renumber the

references in the order they appear in the manuscript. As an example, references 36-38

currently appear in the first paragraph of the Introduction, which requires revision for proper

numbering.

Thank you for pointing that out. I changed the reference order

5/62. Line 11-12: ”Vaccines have been developed and proven successful in preventing severe disease

and death [40], ....” → I suggest change this sentence to ”Vaccines have been developed and

proven successful in inducing seroconversion (cite the following reference 1), preventing severe

disease and death [40], ....” Reference: [1] Safety and Seroconversion of Immunotherapies

against SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis of Clinical Trials.

Pathogens. 2021 Nov 24;10(12):1537. doi: 10.3390/pathogens10121537. PMID: 34959492;

PMCID: PMC8706687.

Added the publication from Kevin Sheng-Kai Ma, as you suggested, although I

am not quite sure if it adds value.

3. Line 51-52: ”Jian et al. reported on the Taiwanese digital system TRACE analysing 487 cases

and 8051 contact persons [12].” → To emphasize the public health implications of these

particular systems, I suggest change this sentence to: ”Jian et al. reported on the Taiwanese

digital system TRACE, analyzing 487 cases and 8051 contact persons [12]. Public health

implications of these systems included surveillance of travel history (cite the following

reference 1) and ensuring an adequate quantity of personal protective equipment (cite the

following reference 2).” References: [1] Integrating travel history via big data analytics under

universal healthcare framework for disease control and prevention in the COVID-19 pandemic.

J Clin Epidemiol. 2021 Feb;130:147-148. doi: 10.1016/j.jclinepi.2020.08.016 [2] Big

Data-driven personal protective equipment stockpiling framework under Universal Healthcare

for Disease Control and Prevention in the COVID-19 Era. Int J Surg. 2020 Jul;79:290-291.

doi: 10.1016/j.ijsu.2020.05.091

Added the two publications from Kevin Sheng-Kai Ma. But as above I dont see

an added value.

Attachment

Submitted filename: rebuttalletter.pdf

pone.0271848.s005.pdf (104.2KB, pdf)

Decision Letter 3

Emanuele Crisostomi

9 Feb 2024

COVID-19 isolation and quarantine orders in Berlin-Reinickendorf (Germany): How many, how long and to whom?

PONE-D-22-19240R3

Dear Dr. Schumacher,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Reviewer #3: In the point-by-point answer to the reviewers the authors have not inserted in their answer the updated text including – using the track changes mode – the indication of what has changed. If you just say for example “we incorporated the suggestion of the reviewer” the reviewer has to look for it himself or herself. Even though there is a version of the total manuscript with tracked changes this means double work for the reviewer because he/she has to search again for the position in the text and identify what has changed. Please, when you write a paper next time and get a review, always include in your point-to-point answer not only your answer but also the respective passage in the text of the manuscript.

Overall the paper has improved since the modification.

I still have a few comments:

I think you need to rethink the structure of the paper somewhat. It is unclear what the objective was, “quantification and analysis” cannot be a goal, it is a method, that is used for a purpose. You say in your response that you think it is important to know “if local agencies follow or dont follow national recommendations”. Why don’t you use that as a goal? something like “During the pandemic the burden of work for local health departments was enormous and the federal public health agency (the Robert Koch Institute) adapted its recommendation several times. We aim to investigate if a local health department was capable to follow the recommendations of the Robert Koch Institute.” With that goal in mind you need to add something in that regard in the abstract and come to a conclusion. To do that you can use a lot of the results that are already in the main part of the paper. A second goal is the estimation of the impact of the efforts of the health department.

I say something to both goals:

If you want to compare the number of RKI-recommended days of isolation or days of quarantine with the number of isolation / quarantine days per person I suggest to put both together in one graph, e.g. as a modification of figure 2 (for example the number of recommended days in a different colour or as a horizontal line), otherwise the reader has to pull it together from several locations (Table 1 and Figure 2) in the paper which is bothersome for the reader.

Regarding the impact I suggest to add to measures/indicators:

(1) the ratio of ncc : nncc which is roughly 4:1 in children and 10:1 in adults, or, the proportion of cases arising from known contacts that were contained (ncc/(ncc+nncc), which is about 80% in children and about 90% for adults.

(2) Another indicator for impact would be ncc/ni, which is the proportion of all cases (with isolation order) who were contained. This is roughly 28% in young children and goes down to 11% in adults.

(3) And a third indicator would be the estimation of the proportion of all infectious days in the population that you had prevented. That indicator combines data of quarantine and isolation. How can you do it:

Step 1: you estimate the number of infectious days (inf-days) in the population which is: ni*inf-days. You have to make an assumption about the infectious period, say day of illness onset -2 until day of illness onset + 5 or so (see e.g. Ke, Nature Microbiology, 2022, or: National Institute for Infectious Disease in Japan (“Active epidemiological investigation on SARS-CoV-2 infection…”). (Nota bene: there is very scarce literature on the shedding kinetic of virus that can be isolated, whereas shedding of virus that can be detected via PCR is abundant, but much different. What you need is the shedding of virus that can be isolated in cell culture)). But you could say you assume illness onset + 5 days (or something else). At any rate this is your denominator.

Step 2: You estimate the number of inf-days prevented. Because ni=ncc + rest, you have to calculate the number of prevented days first for the ncc and then for the “rest” (=ni-ncc). For the ncc the number of prevented inf-days is simply = ncc*inf-days.

For the rest (ni-ncc) the number of prevented inf-days you can calculate as follows:

you calculate the average day after symptom onset when you placed the isolation order. For example it is day 2 after symptom onset. Then the average number of prevented inf-days per person would be 3 days. Then the number of prevented inf-days is: (ni-ncc)*3 days.

Now you have to add the two numbers of prevented inf-days: ncc*inf-days + (ni-ncc)*3 days. This is the numerator.

Step 3: put both in relation: number of prevented inf-days = numerator / denominator.

(This calculation assumes that non-isolated cases would continue to meet their contacts as before their infection; that is a limitation)

I think you said that the day of symptom onset is not part of the database, but you should be able to link it with the cases-database where you have the names and the date of symptom onset. If you cannot link the isolation/quarantine database with the cases database for some reason you can still either take a best guess from your co-workers (“Delphi method”), and/or pull the files of say 100 cases, and look it up. Then you calculate what you need based on these 100 cases.

- I suggest you rephrase your title, for example: “Adherence and impact estimation of COVID-19 isolation and quarantine orders in Berlin-Rheinickendorf, Germany, 2020-2022”

- another small point: Although 2 contacts per case is probably too low Reference 22 (Mossong) is in my eyes not a good comparator for the number of contacts because for sure the population changed their behavior for an extended period of time during 2020-2021.

- Table 2 is doubled.

Reviewer #4: I would like to thank the authors for their thoughtful response to my previous comments. The paper is much improved, and I have no further questions.

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Reviewer #3: No

Reviewer #4: No

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Acceptance letter

Emanuele Crisostomi

27 Feb 2024

PONE-D-22-19240R3

PLOS ONE

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Associated Data

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

    Supplementary Materials

    S1 Table. Detailed table of time periods of relevant recommendations of the Robert Koch Institute for isolation duration, quarantine duration and contact person definition.

    (PDF)

    pone.0271848.s001.pdf (67.5KB, pdf)
    S1 Fig. Exclusion of data entries.

    (PDF)

    pone.0271848.s002.pdf (22.9KB, pdf)
    Attachment

    Submitted filename: rebuttal_letter.pdf

    pone.0271848.s003.pdf (74.6KB, pdf)
    Attachment

    Submitted filename: rebuttal_letter.pdf

    pone.0271848.s004.pdf (74.6KB, pdf)
    Attachment

    Submitted filename: rebuttalletter.pdf

    pone.0271848.s005.pdf (104.2KB, pdf)

    Data Availability Statement

    All code and data-files are available from the github repository https://github.com/jakobschumacher/quarantine-isolation-analysis.


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