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. 2020 Jun 29;148:e130. doi: 10.1017/S0950268820001430

Epidemiological characteristics of COVID-19: a systematic review and meta-analysis

Malahat Khalili 1,2,*, Mohammad Karamouzian 1,3,*, Naser Nasiri 1,2, Sara Javadi 2,4, Ali Mirzazadeh 1,5, Hamid Sharifi 1,2,✉
PMCID: PMC7343974  PMID: 32594937

Abstract

Our understanding of the Coronavirus disease 2019 (COVID-19) continues to evolve and there are many unknowns about its epidemiology. This study aims to synthesise case fatality rate (CFR) among confirmed COVID-19 patients, incubation period and time from onset of COVID-19 symptoms to first medical visit, intensive care unit (ICU) admission, recovery, and death. We searched MEDLINE, Embase, Google Scholar, and bibliographies of relevant articles from 01 December 2019 to 11 March 2020 without any language restrictions. Quantitative studies that recruited people with confirmed COVID-19 diagnosis were included. Two independent reviewers extracted the data. Out of 1675 non-duplicate studies, 43 were included in the meta-analysis. The pooled mean incubation period was 5.68 (99% confidence interval [CI]: 4.78, 6.59) days. The pooled mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.92 (95% CI: 3.95, 5.90), ICU admission was 9.84 (95% CI: 8.78, 10.90), recovery was 18.55 (95% CI: 13.69, 23.41), and death was 15.93 (95% CI: 13.07, 18.79). Pooled CFR among confirmed COVID-19 patients was 0.02 (95% CI: 0.02, 0.03). We found that the incubation period and lag between the onset of symptoms and first clinical visit for COVID-19 are longer than other respiratory viral infections including Middle East respiratory syndrome and severe acute respiratory syndrome; however, the current policy of 14 days of mandatory quarantine for everyone potentially exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be too conservative. Longer quarantine periods might be more justified for extreme cases.

Key words: Coronavirus, COVID-19, epidemiology, pandemic

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in a few unusual pneumonia patients linked to the Wuhan seafood wholesale market in China in December 2019 [1]. However, it soon grew out of China and the Coronavirus disease 2019 (COVID-19) was declared a pandemic on 11 March 2020, and has been reported in 216 countries, areas, or territories [2]. While the epidemic has slowed down in China due to the strict quarantine and preventive regulations, the numbers of COVID-19 patients (i.e. 10021401 as of 28 June, 2020) and confirmed deaths (i.e. 499913 as of 28 June, 2020) are rapidly increasing [2] and have surpassed that of other viruses in the coronavirus family with similar genomes to SARS-CoV-2. For example, SARS which emerged in 2003, infected 8098 patients and caused 774 deaths across 29 countries. The Middle East respiratory syndrome (MERS) which appeared in 2012, led to 2494 patients and 858 deaths across 27 countries [3–6]. The healthcare systems in many countries such as the USA, Spain, Italy, France, UK, Turkey and Iran have been overwhelmed and struggling with the soaring number of patients [7].

Although our understanding of COVID-19's epidemiology is evolving, it is assumed that SARS-CoV-2 is mainly transmitted via droplets and close contacts with people carrying the virus [2]. However, recent reports have also proposed the possibility of the virus being contracted via various surfaces, gastrointestinal transmission [8] and potentially airborne exposures [2, 9]. Based on the existing evidence, elderly population, those with suppressed immune systems and underlying metabolic, cardiovascular or respiratory diseases are at an increased risk for adverse outcomes; however, recent reports from outside China, point to a considerable risk of severe outcomes among the general adult population (i.e. <65 years old) [10, 11].

As we continue to learn more about COVID-19 and its characteristics, there are many unknowns about its epidemiology such as hospitalisation and recovery-related outcomes that are critical for healthcare system preparedness [12, 13]. For example, the mean number of incubation days for COVID-19 varies greatly across the existing literature ranging from 2.5 [14] to >20 days [15, 16]. Our understanding of time from contracting the disease to recovery or death is even more limited. In this systematic review and meta-analysis, we tried to identify the studies that recruited patients diagnosed with COVID-19 and calculate pooled estimates for several epidemiological and clinical outcomes to help provide an overall picture of the epidemiological characteristics of COVID-19. Findings of this study could help inform the ongoing public health and public policy practices across the world.

Methods

The details of inclusion criteria and our analytical approach were designed a priori and are documented in Open Science Framework (https://osf.io/a3k94/).

Literature search

Following the Systematic Reviews and Meta-Analyses (PRISMA) checklist (see Supplementary Table S1) and the Peer Review of Electronic Search Strategies (PRESS) guideline [17, 18], we searched PubMed, Embase and Google Scholar from 1 December 2019 to 11 March 2020 for studies that measured and reported several characteristics of COVID-19 (e.g. incubation period, hospitalisation, death). Search terms were combined using appropriate Boolean operators and included subject heading terms/keywords relevant to COVID-19 (e.g. novel coronavirus, sars-cov2, coronavirus disease). Please see Supplementary Table S2 for our sample search strategy.

Inclusion criteria

Quantitative studies were included in the review if they reported incubation period of of SARS-CoV-2 as well as time from onset of the symptoms to first medical visit, intensive care unit (ICU) admission, recovery (as defined by studies' authors) or death. Studies were also included if they reported the number of deaths among patients with a confirmed COVID-19 diagnosis. Studies were included in the meta-analysis if they provided data on the above-mentioned outcomes along with their standard error and sample size. Case-reports with a sample size of one were removed from the meta-analysis as they did not provide any dispersion estimate. Studies were not excluded based on language, location or measurement method. Given that this study used secondary data and involved no interaction with humans, no ethics approval was required.

Study selection

Two authors (SJ and NN) completed the abstract and full-text screening, independently. The full-texts of citations that met our inclusion criteria or were unclear were screened by two independent reviewers (SJ and NN). Disagreements over the inclusion of studies were resolved through discussion or by arbitration with the senior author (HS). Duplicate records were excluded.

Data extraction

Data were extracted independently by the two authors (SJ and NN) and discrepancies were resolved through discussion or by arbitration with the senior author (HS). Data were extracted on publication date, study type (e.g. cross-sectional, case-series, cohort), location, sample size, as well as patients' age and sex. We also extracted data on exposure history, X-ray and computed tomography scan findings, symptoms and underlying conditions in addition to the main outcomes of interests including the number of deaths among confirmed COVID-19 patients (i.e. case fatality rate [CFR]), incubation period and time from onset of COVID-19 symptoms to first medical visit, ICU admission, recovery, and death.

Statistical analysis

Meta-analysis was performed using STATA's (V.15.1) metan (for numerical variables) and metaprop (for binary variables) commands. The 95% confidence intervals (CI) for binary variables were computed using the exact binomial method. Heterogeneity between the studies was assessed using both the I2 statistic with a cut-off of 50% and the χ2 test with P-value <0.10 [19]. As all results turned out to be significantly heterogeneous, we used random-effects models to calculate the pooled point estimate and 95% CI for the CFR, mean time from onset of COVID-19 symptoms to first medical visit, ICU admission, recovery, and death. For the mean incubation period, we estimated 99% CI. We also conducted a random-effects meta-regression using STATA's metareg command to identify the sources of heterogeneity and explored the effect of study-level covariates where data were available (Supplementary Table S3). Meta-regression was considered when there were at least 10 studies included in the meta-analysis [20]. A two-sided P-value <0.05 was considered as statistically significant.

Results

Participants and study characteristics

We found a total of 1675 non-duplicate studies, 57 of which were included in the qualitative synthesis and 43 were included in the meta-analysis (Fig. 1). A description of the main characteristics of the included studies is provided in Table 1. The 57 studies included 27 cross-sectional, one case-control, one retrospective cohort and 28 case series/case report studies with sample sizes ranging greatly from one in case-reports to 58 182 for a study in the Hubei province [21]. Inclusion criteria varied greatly across the studies but most study participants were hospitalised patients living or travelling from various provinces in China. Median (range) age of the participants was 46.2 (range: 17 days to 78.5 years) and about 60% were male. Most studies were conducted between January and February 2020. Clinical and epidemiological characteristics of the patients included in the study are presented in Table 2. Among studies that reported exposure history among their participants, most patients were directly or indirectly traced back to the city Wuhan (e.g. lived in Wuhan or had recently travelled to Wuhan) and the Huanan seafood market in Hubei province, China. Several cases of contracting SARS-CoV-2 through close contacts with family members were also reported across the studies. Frequent CT or X-ray findings included thickened texture of the lungs, bilateral focal consolidation, lobar consolidation, ground-glass opacity, patchy consolidation, and unilateral/bilateral pneumonia. Common symptoms reported across the studies included fever, cough, shortness of breath, and fatigue/weakness. Only 15 studies reported some information about the pre-existing conditions of the patients; most of whom had metabolic and cardiovascular underlying conditions.

Fig. 1.

Fig. 1.

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PRISMA flowchart of screened and included studies.

Table 1.

Characteristics of the included studies in the systematic review

First author Publication date (DD-MM-YY) Study setting/location Study type Sample size Age; mean/range Male proportion
Chan [22] 24-Jan-20 China, Shenzhen Case series 6 46.17 0.50
Li [23] 29-Jan-20 China, Wuhan Cross-sectional 425 55.5 0.56
Chen [1] 30-Jan-20 China, Wuhan Cross-sectional 99 55.5 0.68
Holshue [24] 31-Jan-20 USA, Washington Case-reporta 1 35 1.00
Wu [25] 3-Feb-20 China, Wuhan Case-report 1 41 1.00
Kim [26] 3-Feb-20 South Korea, Incheon Case-report 1 35 0.00
Cai [27] 4-Feb-20 China, Shanghai Case-reportb 2 7 0.67
Lin [28] 4-Feb-20 China, Jiangxi province Case-report 2 37 1.00
Backer [29] 6-Feb-20 China, Wuhan Cross-sectional 88 2 to 72 0.65
Ki [30] 9-Feb-20 South Korea Cross-sectional 28 42.1 0.54
Jiang [31] 24-Feb-20 China Cross-sectional 50 NR NR
Chen [32] 11-Feb-20 China, Wuhan Case-report 1 1 1.00
Thompson [33] 11-Feb-20 China Cross-sectional 47 47 0.63
Zhang [34] 11-Feb-20 China, Xiaogan Case-report 1 0.25 (3 months) 0.00
Duan [35] 12-Feb-20 China, Wuhan Case-report 1 46 0.00
Stoecklin [36] 13-Feb-20 France, Bordeaux Case-report 3 36.3 0.67
Huang [37] 15-Feb-20 China, Wuhan Cross-sectional 41 49.34 0.73
Zhang [14] 15-Feb-20 China, Beijing Case series 9 35.3 0.56
Lim [38] 17-Feb-20 South Korea, Goyang Case-report 1 54 1.00
Linton [39] 17-Feb-20 China, multiple cities Cross-sectional 276 30–59 (>50%) 0.58
COVID-19 Response Team [40] 17-Feb-20 China, multiple cities Cross-sectional 44 672 30–69 (77.8%) 0.51
Zeng [41] 17-Feb-20 China, Wuhan Case-report 1 0.046 (17 days) 1.00
Yu [42] 18-Feb-20 China, Shanghai Case-report 4 74.25 0.50
Xu [43] 18-Feb-20 China, Beijing Case-report 1 50 1.00
Fang [44] 19-Feb-20 China, Chengdu Case-report 1 47 1.00
Wang [45] 20-Feb-20 China, Wuhan Cross-sectional 138 55.3 0.54
Zhu [46] 20-Feb-20 China, Wuhan Case-report 3 47.33 0.67
Bai [47] 21-Feb-20 China, Anyang Case series 6 34.75 0.17
Hao [48] 21-Feb-20 China, Shaanxi Case-report 1 58 1.00
Shi [49] 24-Feb-20 China, Wuhan Cross-sectional 81 49.5 0.52
Cheng [50] 26-Feb-20 Taiwan, Taoyuan Case-report 1 55 0.00
Li [51] 26-Feb-20 China, Mainland China Cross-sectional 44 653 NR NR
26-Feb-20 China, Hubei Cross-sectional 33 366 NR NR
Yang [52] 26-Feb-20 China, Wenzhou Cohort 149 45.11 0.54
Shrestha [53] 27-Feb-20 Nepal, Kathmandu Case-report 1 32 1.00
Tian [54] 27-Feb-20 China, Beijing Cross-sectional 262 47.5 0.48
Guan [55] 28-Feb-20 China, 30 provinces Cross-sectional 1099 46.7 0.58
Lillie [56] 28-Feb-20 UK Case-report 2 36.5 0.50
Wu [57] 29-Feb-20 China, Jiangsu province Cross-sectional 80 46.1 0.49
Song [58] 1-Mar-20 China Cross-sectional 11 791 NR NR
Cheng [59] 2-Mar-20 China, Henan province Cross-sectional 1079 46.6 0.53
Peng [60] 2-Mar-20 China, Wuhan Cross-sectional 112 61.3 0.47
Dey [21] 3-Mar-20 China, Hubei province Cross-sectional 58 182 NR NR
China, Other provinces Cross-sectional 12 264 NR NR
Outside of China Cross-sectional 425 NR NR
Ruan [61] 3-Mar-20 China, Wuhan Case control 66 45–75 (>50%) NR
Young [62] 3-Mar-20 Singapore Cross-sectional 18 49.5 0.50
Chen [63] 5-Mar-20 China, Guangdong Case-report 1 46 0.00
Cheng [64] 5-Mar-20 China, Hong Kong Cross-sectional 42 57.8 0.48
Qiu [65] 5-Mar-20 China, Zhengzhou Case series 8 25.9 0.50
Rothe [66] 5-Mar-20 Germany, Munich Case series 5 NR NR
Spiteri [67] 5-Mar-20 WHO European Region Cross-sectional 38 41.75 0.66
Wang [68] 5-Mar-20 China, Wuhan Case-report 2 78.5 0.50
Wang [69] 5-Mar-20 China, Zhengzhou Cross-sectional 18 41 0.56
Wu [70] 5-Mar-20 China, Tianjin Cross-sectional 40 44.0 0.33
Yang [71] 5-Mar-20 China Cross-sectional 325 8 months to 90 years 0.49
Lauer [72] 10-Mar-20 China, outside Hubei province Cross-sectional 181 44.67 0.60
Outside mainland China Cross-sectional 108 NR NR
Tong [73] 17-May-20c China, Zhoushan Case-report 3 33 1.00
Arashiro [74] 17-Jun-20c Japan, Cruise ship Case-report 2 31 0.50
Liu [75] 17-Jun-20c China, Shenzhen Cross-sectional 365 46.2 0.50
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a

Studies with a sample size less than or equal to four patients were labelled as case-reports [76].

b

A 7-year-old-boy and his parents.

c

Studies are in press and will be published in future issues of the respective journals.

Table 2.

Medical and epidemiological characteristics of the studies included in the systematic review

First author Exposure history X-ray/CT findings Symptoms Underlying conditions Incubation perioda Time to first clinical visitb Time to ICU admission Time to recovery Time to death Death
Chan [22] Family cluster;
History of travel to Wuhan; No contact with animals; Huanan seafood wholesale market in Wuhan.		 14.3% Ground-glass lung opacities; 85.7% Pulmonary infiltrates and multifocal patchy ground-glass opacities, especially around the peripheral parts of the lungs 71.4% Fever; 57.1% Cough; 42.9% Generalised weakness;
14.3% Nasal congestion; 14.3%
Sneezing; 14.3% Rhinorrhoea; 14.3% Sore throat; 14.3% Pleuritic chest pain; 28.6% Diarrhoea		 28.6% Hypertension;
14.3% Benign intracranial tumour; 14.3% Chronic sinusitis; 14.3% Diabetes		 4.5 (0.64) 7.8 (0.74) NR NR NR NR
Li [23] 11.8% Huanan Seafood Wholesale Market;
4.0% Other wet market but not Huanan Seafood Wholesale Market; 15.3% Contact with another person with respiratory symptoms;
49.9% No exposure to either market or person with respiratory symptoms		 NR NR NR 5.2 (0.74) 9.7 (0.22) NR NR NR NR
Chen [1] 49% Huanan seafood market 25% Unilateral pneumonia; 74% Bilateral pneumonia; 14% Multiple mottling and ground-glass opacity 83% Fever; 82% Cough;
31% Shortness of breath; 11% Muscle pain; 9% Confusion; 8% Headache; 5% Sore throat; 4% Rhinorrhoea; 2% Chest pain; 2% Diarrhoea; 1% Nausea and vomiting; 90% More than one sign or symptom; 15% Fever, cough and shortness of breath		 51% Chronic medical illness; 40% Cardiovascular and cerebrovascular diseases;
11% Digestive system disease;
13% Endocrine system disease;
1% Malignant tumour; 1% Nervous system disease; 1% Respiratory system disease		 NR NR NR NR NR 11
Holshue [24] History of travel to Wuhan Illness day 4: No thoracic abnormalities;
Illness day 9: Increasing left basilar opacity		 Cough; Fever; Nausea and vomiting Hypertriglyceridemia NR 3 (0.0) NR 15 (0.0) NR NR
Wu [25] Worked at a local indoor seafood market X-ray: Illness day 6: Abnormal with air-space shadowing such as ground-glass opacities, focal consolidation and patchy consolidation in both lungs;
Illness day 11: Bilateral diffuse patchy and fuzzy shadow;
CT: Illness day 6: Bilateral focal consolidation; Lobar consolidation and patchy consolidation, especially in the lower lung		 Fever; Cough; Sputum production; Dizzy; Weakness; Chest tightness; Dyspnoea No NR 6 (0.0) 9 (0.0) NR NR NR
Kim [26] Living in Wuhan Initial X-ray: No infiltrations;
Illness day 8: Chest infiltrates in the right lower lung field;
CT: Illness day 4: Multiple ground-glass opacities in both subpleural spaces		 Fever; Chill; Myalgia; Nasal Congestion; Cough; Sputum; Pleuritic chest discomfort; Watery Diarrhoea Obese (body mass index, 33.4 kg/m2) NR 1 (0.0) NR 13 (0.0) NR NR
Cai [27] History of travel to Wuhan;
Familial contacts		 X-ray in child: Thickened texture of both lungs; Blurred right inner lung zone and left posterior region of the heart; Without obvious patch shadows Fever; Cough; Nasal secretions.
Mother of the child: Asymptomatic		 NR NR 2.5 (1.0) NR 7 (0.0) NR NR
Lin [28] History of travel to Wuhan; Close contact CT: Patient 1: Multiple regions of patchy consolidation and ground-glass opacities with indistinct border in both lungs;
Distributed lesions along the bronchial bundles or within the subpleural lung regions.
Patient 2: Focal consolidation along broncho-vascular bundles in right lower lung lobe; Ground-glass opacities in subpleural regions of a left lower lung lobe		 Fever; Cough; Throat discomfort No NR 2.5 (0.5) NR NR NR NR
Backer [29] NR NR NR NR 6.4 (0.54) NR NR NR NR NR
Ki [30] 34.6% Arrived from Wuhan; 46.2% Close contact; 3.9% History of travel to Japan; 3.9% History of travel to Thailand; 7.7% Attended a conference in Singapore NR Mostly fever; Sore throat; Cough; Chill; Fatigue; Muscle pain NR 3.9 (0.47)
Range: 3–15		 NR NR 13 (0.31) NR NR
Jiang [31] NR NR NR NR 4.9 (0.28) NR NR NR NR NR
Chen [32] Exposed to infection during the consultation X-ray: Illness day 2: Large blurred images of right upper and lower right lungs;
Illness day 7: Partial absorption of right lower lobe pneumonia, right upper lobe atelectasis;
CT: Illness day 2: Enhanced texture of lungs; Large consolidating shadows in right lung; Ground glass shadows		 Intermittent Diarrhoea; Vomiting; Fever; Shortness of breath; Poor mental response; Lethargy; Poor appetite NR NR 1 (0.0) 6 (0.0) 17 (0.0) NR NR
Thompson [33] NR NR NR NR NR 2.15 (0.43) NR NR NR NR
Zhang [34] Unknown X-ray: Illness day 1: thickened texture of lungs; a small patch-like shadow in the lower right lung field;
CT: Illness day 6: Enlarged lung texture		 Fever; Cough; Foaming NR NR 0 (0.0) NR 14 (0.0) NR NR
Duan [35] NR CT: Bilateral and peripheral ground-glass opacities in the superior segments of both lower lobes; Without sparing of subpleural regions. Fever NR NR 7 (0.0) NR 20 (0.0) NR NR
Stoecklin [36] Arrived from Wuhan NR 100% Fever; 33.4% Headaches; 100% Cough; 66.7% Fatigue; 33.4% Conjunctivitis; 66.7% Chills NR NR 4.34 (1.8) 10 (0.0) 22 (2.0) NR NR
Huang [37] 66% Direct exposure to Huanan seafood market 98% Bilateral involvement;
CT in ICU patients on admission: Bilateral multiple lobular; Subsegmental areas of consolidation		 98% Fever; 76% Cough; 44% Myalgia or Fatigue; 28% Sputum production; 8% Headache; 5% Haemoptysis; 3% Diarrhoea; 55% Dyspnoea 20% Diabetes; 5% Hypertension; 15% Cardiovascular disease;
2% Chronic obstructive pulmonary disease; 2% Malignancy; 2% Chronic liver disease		 NR 7 (0.15) 10.5 (0.35) NR NR 6
Zhang [14] 66.7% History of travel to Wuhan; 11.1% History of travel to Xiaogan, Hubei; 11.1% Clinician at 3 hospitals in Beijing;
11.1% Familial transmission		 X-ray: 22.2% A little exudation of lung;
CT: 77.8% Multiple ground glass shadows in the lungs; 33.4% Accompanied by consolidation on the basis of ground glass shadows		 88.9% Fever; 55.6% Cough; 44.5% Sore throat; 44.5% Fatigue; 11.1% Nasal congestion; 11.1% Tonsil enlargement; 11.1% Rhinorrhoea 11.12% Diabetes 2.5 (0.65) 4.6 (0.85) NR NR NR NR
Lim [38] Living in Wuhan CT: Small consolidation in the right upper lobe and ground-glass opacities in both lower lobes Fever; Dry cough; Loose stool; Chilling; Myalgia; Muscle pain No NR 3 (0.0) NR 19 (0.0) NR NR
Linton [39] Direct or indirect exposure to Wuhan and Hubei Province NR NR NR 5.6 (0.33) 6.2 (0.71) NR NR 14.5 (1.14) 39
COVID-19 Response Team [40] 68.6% living or going to Wuhan or in close contact with Wuhan patients NR NR NR NR NR NR NR NR 1023
Zeng [41] Family transmission X-ray: A little right upper lung opacities;
CT: No increase in hilar shadows; Enhanced texture of both lungs, and even distribution		 Sneezing; Intermittent vomiting; Decreased mental reaction; Milk intake No NR 7 (0.0) NR 13 (0.0) NR NR
Yu [42] Arrived from Wuhan;
Family transmission		 CT: Patient 1: Interstitial hyperplasia with infection in both of lungs; Chronic bronchitis; Emphysema; Pulmonary bullae of a lingual segment of the left lung; Pulmonary hypertension in both lungs; Increased heart shadow; Calcification of the aorta and aortic wall.
Patient 2: 2 Ground-glass opacities on the inferior lobe of the right lung		 100% Fever; 25% Poor appetite; 25% Dry cough; 25% Chills Patient 1: Hypertension, Heart disease; Chronic obstructive pulmonary disease NR 0.5 (2.9) 1 (0.0) NR 5 (0.0) 1
Xu [43] History of travel to Wuhan X-ray: Illness day 8: Multiple patchy shadows in both lungs;
Illness day 12: Progressive infiltrate; Diffuse gridding shadow in both lungs		 Fever; Chills; Cough; Fatigue; Shortness of breath NR NR 7 (0.0) NR NR 14 (0.0) 1
Fang [44] Family transmission CT: Ground-glass opacities; Consolidation; or Both in bilateral lungs; ‘Halo sign’ in the basal segment of the lower lobe of the right lung Cough; Sputum production; Sore throat; Throbbing headache NR NR 3 (0.0) NR NR NR NR
Wang [45] 8.7% were exposed to Huanan Seafood Wholesale Market CT: 100% Bilateral involvement 98.6% Fever; 69.6% Fatigue; 59.4% Dry cough; 39.9% Anorexia; 34.8% Myalgia; 31.2% Dyspnoea; 26.8% Expectoration; 17.4% Pharyngalgia; 10.1% Diarrhoea; 10.1% Nausea; 9.4% Dizziness; 6.5% Headache; 3.6% Vomiting; 2.2% Abdominal pain 31.2% Hypertension; 14.5% Cardiovascular disease; 10.1% Diabetes;
7.2% Malignancy; 5.1% Cerebrovascular disease; 2.9% COPD; 2.9% Chronic kidney disease; 2.9% Chronic liver disease; 1.4% HIV infection		 NR NR NR NR NR 6
Zhu [46] Frequently exposed to Huanan Seafood Wholesale Market CT: Illness day 8: Bilateral fluffy opacities; Illness day 11: Bilateral fluffy opacities in both images, with increased in density, profusion and confluence Fever; Cough; Chest discomfort NR NR 5.5 (1.5) NR 26.5 (1.5) 14 (0.0) 1
Bai [47] An asymptomatic carrier arrived from Wuhan;
Family transmission		 CT: Multifocal ground-glass opacities; Subsegmental areas of consolidation and fibrosis 16% Asymptomatic; Fever; Respiratory symptoms; Sore throat NR 12.17 (2.06) NR NR NR NR NR
Hao [48] Arrived from Wuhan CT: At admission: Multiple patchy; Cloud-like high-density shadows in the dorsal segment of the right lower lobe;
4 days after admission: Large ground glass-like high-density shadows on the dorsal segment of the right lung; Patchy cloud-like high-density shadows and consolidation shadows on the left lung		 Fever; Sore throat; Fatigue NR 4 (0.0) 1 (0.0) NR NR NR NR
Shi [49] 38% Direct exposure to Huanan seafood market;
19% Healthcare workers having close contact with patients; 9% Familial transmission;
35% Without any obvious history of exposure		 All patients with abnormal CT imaging features; All lung segments can be involved, and 27% predilection for the right lower lobe;
mean number of segments involved: 10.5		 73% Fever; 42% Dyspnoea; 22% Chest tightness; 59% Cough; 19% Sputum; 26% Rhinorrhoea; 1% Anorexia; 9% Weakness; 5% Vomiting; 6% Headache; 2% Dizziness; 4% Diarrhoea 11% Chronic pulmonary disease; 12% Diabetes; 15% Hypertension; 4% Chronic renal failure; 10% Cardiovascular disease; 7% Cerebrovascular disease; 5% Malignancy; 9% Hepatitis or Liver cirrhosis NR NR NR 23.2 (0.67) 18.7 (5.7) 3
Cheng [50] Arrived from Wuhan X-ray: Progression of prominent bilateral perihilar infiltration; Patchy opacities at bilateral lungs;
CT: Persistent multifocal ground-glass opacities with or without superimposed reticulation; Mild fibrotic change at bilateral lungs, including peripheral subpleural regions of both lower lobes;
Small irregular opacities		 Sore throat; Dry cough; Fatigue; Fever Hypothyroidism NR 9 (0.0) NR 28 (0.0) NR NR
Li [51] NR NR NR NR NR NR NR NR NR 1113
NR NR NR NR NR NR NR NR NR 1068
Yang [52] 53.7% Stayed in Wuhan;
3.4% Stay in Hubei province except for Wuhan;
32.9% Contact with people from Hubei province;
10.1% No relation with Hubei province		 CT: 3 Involved pulmonary lobes; 6 Involved segments in each patient;
Segment 6 and 10 most involved;
2.1% Segments presented ground-glass opacities; 26.8% Segments presented mixed opacity; 7.2% Segments presented consolidation;
More localised lesions in the periphery rather than the centre of the lung; More patchy lesions than oval lesions		 76.5% Fever; 58.4% Cough; 32.2% Expectoration; 1.3% Dyspnoea; 3.4% Muscle pain; 8.7% Headache; 14.1% Sore throat; 3.4% Snotty; 3.4% Chest pain; 10.7% Chest tightness; 14.1% Chill; 7.4% Diarrhoea; 1.3% Nausea and Vomiting 18.8% Cardio-cerebrovascular disease; 5.4% Digestive system disease; 6.1% Endocrine diseases; 1.3% Malignant tumour; 0.7% Respiratory system diseases; 2.7% Others NR 6.8 (5.0)
Median (IQR)		 NR NR NR 0
Shrestha [53] Arrived from Wuhan NR Fever NR NR 10 (0.0) NR 14 (0.0) NR NR
Tian [54] 40.5% Arrived from; 49.2% Contact with a symptomatic case in the previous 14 days;
67.2% Cluster case		 NR 82.1% Fever; 45.8% Cough; 26.3% Fatigue; 6.9% Dyspnoea; 6.5% Headache. NR 6.7 (5.2)
Median (IQR)		 4.5 (3.7)
Median (IQR)		 NR NR NR 3
Guan [55] 43.9% Living in Wuhan;
1.9% Contact with wildlife; 31.3% Arrived from Wuhan; 72.3% Contact with Wuhan residents		 X-ray: 20.1% Ground-glass opacity; 28.1% Local patchy shadowing; 36.5% Bilateral patchy shadowing; 4.4% Interstitial abnormalities;
CT: 56.4% Ground-glass opacity; 41.9% Local patchy shadowing; 51.8% Bilateral patchy shadowing; 14.7% Interstitial abnormalities		 88.7% Fever; 0.8% Conjunctival Congestion; 4.8% Nasal congestion; 13.6% Headache; 67.8%% Cough; 13.9% Sore throat; 33.7% Sputum production; 38.1% Fatigue; 0.9% Haemoptysis; 18.7% Shortness of breath; 5.0% Nausea or Vomiting; 3.8% Diarrhoea; 14.9% Myalgia or Arthralgia; 11.5% Chills 1.1% Chronic obstructive pulmonary disease; 7.4% Diabetes; 15.0% Hypertension; 2.5% Coronary heart disease; 1.4% Cerebrovascular disease; 2.1% Hepatitis B infection, 0.9% Cancer, 0.7% Chronic renal disease, 0.2% Immunodeficiency 4 (0.02)
Range: 2–7		 NR NR NR NR 15
Lillie [56] Arrived from Wuhan; Close household contact NR Fever; Malaise; Dry cough; Sinus congestion; Sore throat; Sinus congestion NR NR 3 (1.0) NR 8.5 (0.5) NR NR
Wu [57] 100% Arrived from Wuhan 45.0% Bilateral pneumonia; 23.7% Unilateral pneumonia; 31.2% No abnormal density shadow 78.7% Fever; 63.7% Cough; 37.5% Shortness of breath; 22.5% Muscle pain; 16.2% Headache and mental disorder symptoms; 13.7% Sore throat; 6.1% Rhinorrhoea; 3.7% Chest pain; 1.2% Diarrhoea; 1.2% Nausea and vomiting; 82.5% More than one sign or symptom 31.2% Cardiovascular and cerebrovascular diseases; 6.2% Endocrine system diseases; 3.7% Digestive system disease; 1.2% Respiratory system diseases; 1.2% Malignant tumour; 1.2% Nervous system diseases; 1.25% Chronic kidney disease; 1.2% Chronic liver disease NR NR NR NR NR 0
Song [58] NR NR NR NR 5.01 (0.35) NR NR NR NR NR
Cheng [59] 48% Short stay in Wuhan; 35.4% Arrived from Wuhan; 35.4% Close contact; 16.9% No clear case contact history NR 91.4% Fever; 7.3% Fatigue; 18.2% Cough; 3.1% Sputum; 1.2% Chills; 3.5% Rhinorrhoea; 1.3% Nasal Congestion; 4.0% Dry throat; Sore throat; 3.5% Headache; 1% Chest pain; 3% Shortness of breath; 3.5% Digestive symptoms NR NR NR NR NR NR 19
Peng [60] NR NR 90.2 Fever; 67.9% Cough; 63.4% Fatigue or myalgia; 33.9% Chest pain and tightness; 13.4% Diarrhoea; 11.6% Difficulty breathing; 8.9% Stuffy nose; 8.9% Other 20.5% Diabetes; 82.1% Hypertension; 55.4% Coronary heart disease; 35.7% Heart failure NR 9.84 (0.56) NR NR NR 17
Dey [21] NR NR NR NR NR NR NR NR NR 1696
NR NR NR NR NR NR NR NR NR 69
NR NR NR NR NR NR NR NR NR 5
Ruan [61] Residents of Wuhan NR NR NR NR NR NR NR 18.42 (2.27)
Young [62] 100% History of travel to Wuhan; 5.6% Huanan seafood market; 17% Contact with a healthcare facility in China; 50% Contact with a known case of COVID-19 33% Abnormal chest radiograph finding or lung crepitations; bilateral diffuse airspace opacities; 67% No pulmonary opacities 72% Fever; 83% Cough; 6% Diarrhoea; 12.5% Rhinorrhoea; 61% Sore throat; 11% Shortness of breath NR NR 2.39 (0.61) 9 (3) 14.75 (1.22) NR 0
Chen [63] History of travel to Wuhan CT: Multiple patchy ground glass opacities in bilateral subpleural areas Fever; Sore throat; Cough; Chest distress NR NR 7 (0.0) NR 23 (0.0) NR NR
Cheng [64] 33.4% History of travel to mainland China; 4.8% Wet or seafood market; 66.7% Familial transmission NR NR NR NR NR NR NR NR 1
Qiu [65] Arrived from Wuhan; Familial transmission NR 75% Fever; 37.5% Cough; 12.5% Nasal congestion; 25% Rhinorrhoea; 25% Sneezing; 12.5% Sore throat; 12.5% Tears; 12.5% Diarrhoea; 12.5% Chills; 12.5% Headache; 12.5% Pharyngeal discomfort; 12.5% Rapid heartbeat NR 9.34 (0.49) 1.75 (0.45) NR NR NR NR
Rothe [66] Close contact in workplace NR Fever; Sore throat; Myalgia; Chills NR 4.5 (0.65) 2.75 (0.48) NR NR NR NR
Spiteri [67] 40% Arrived from China; 60% Infected in Europe NR 6.4% Asymptomatic; 64.5% Fever; 45.2% Cough; 25.8% Weakness; 16.3% Headaches; 6.4% Sore throat; 6.4% Rhinorrhoea; 6.4% Shortness of breath NR NR 3.7 (0.46) NR NR NR 4
Wang [68] NR CT: Multiple ground glass Shadow Intermittent fever; Intermittent cough; Chest tightness; Shortness of breath; Muscle pain In one patient: coronary heart disease NR 14.5 (1.5) NR NR NR NR
Wang [69] 72.2% history of visiting Wuhan; Familial transmission CT: Ground glass opacities with consolidations 94.4% Fever; 55.6% Cough; 22.2% Shortness of breath; 5.6% Haemoptysis; 11.1% Muscle pain; 5.6% Headache; 5.6% Sore throat; 16.7% Diarrhoea; 5.6% Nausea and vomiting 16.7% Cardiovascular disease; 27.8% Hypertension; 16.7% Diabetes; 11.1% Stroke; 5.6% Malignant tumour NR 7.75 (0.77) NR NR NR NR
Wu [70] Close contact in a department store NR 95.0% Fever; 35.0% Cough; 27.5% Fatigue; 25.0% Muscle soreness; 15% Diarrhoea; 12.5% Rhinorrhoea; 10% Nasal congestion; 7.5% Headache; Sneezing, Sputum; Nausea; Abdominal pain; 5% Dry mouth; Pharyngeal discomfort; Chest tightness; Asthma; Dizziness; Vomiting NR 7.25 (0.72) NR NR NR NR 2
Yang [71] 79% Family transmission; 10% Meals; 6% In a mall or supermarket; 3% Cases of work; 2% Cases of transportation NR NR NR 8.75 (0.26) NR NR NR NR NR
Lauer [72] 46.4% Resident of Hubei province; 42.5% History of travel to Wuhan; 11.0% Unknown NR NR NR 5.15 (0.33) NR NR NR NR NR
NR NR NR NR 5.7 (0.66) NR NR NR NR NR
Tong [73] Close contact with a visitor from Wuhan; Familial transmission NR Fever; Cough; Skin tingling; Myalgia NR NR 4 (2.0) NR NR NR NR
Arashiro [74] Close contact Not clinically significant Throat dryness and soreness; Throat redness; Slight cough; Fever NR NR 4.0 (0.99) NR 22.5 (0.5) NR NR
Liu [75] 43% Close contact; 51% Arrived from Hubei province; 6% Unknown NR NR NR 6.0 (0.70)
Range: 1–16		 3.89 (0.11) NR NR NR NR
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a

Mean (s.e.) day unless specified otherwise.

b

Time refers to time from onset of symptoms.

Mean incubation period

The estimated mean incubation period obtained from the included studies and the pooled mean are presented in Figure 2. Out of the 18 studies included in the meta-analysis, 15 were conducted in China. The pooled mean incubation period was 5.68 (99% CI: 4.78, 6.59) days. Heterogeneity testing (I2 = 98.4%) revealed notable differences among the included studies in the meta-analysis. Multivariate meta-regression results showed no significant differences in incubation period time by country (China vs. others, Adjusted β = 1.76; P-value = 0.375), age (Adjusted β = −1.16; P-value = 0.151) or male percentage of the participants (Adjusted β = −12.35; P-value = 0.058).

Fig. 2.

Fig. 2.

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Incubation period of COVID-19.

Mean time from onset of symptoms to first clinical visit

The estimated mean number of days from the onset of COVID-19 symptoms to first clinical visit was 4.92 (95% CI: 3.95, 5.90). As shown in Figure 3, out of the 24 studies included in the meta-analysis, only six were conducted outside China. Heterogeneity testing (I2 = 98.3%) revealed notable differences among the included studies in the meta-analysis. Multivariate meta-regression results showed no significant differences in time from onset of symptoms to first clinical visit by country (China vs. others, Adjusted β = 1.51; P-value = 0.411), age (Adjusted β = 0.92; P-value = 0.153) or male percentage of the participants (Adjusted β = −2.60; P-value = 0.626).

Fig. 3.

Fig. 3.

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Time from onset of symptoms to first clinical visit for COVID-19 patients.

Mean time from onset of symptoms to ICU admission

The estimated mean number of days from the onset of COVID-19 symptoms to ICU admission was 9.84 (95% CI: 8.78, 10.90), an estimate that was derived from one study in Singapore and two studies in Wuhan, China (Fig. 4).

Fig. 4.

Fig. 4.

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Time from onset of symptoms to ICU admission for COVID-19 patients.

Mean time from onset of symptoms to recovery

The estimated mean number of days from the onset of symptoms to recovery was reported in seven studies and the resulting pooled mean was 18.55 (95% CI: 13.69, 23.41). Only two studies were conducted in China and the rest were completed in France, South Korea, the UK, Singapore and Japan (Fig. 5).

Fig. 5.

Fig. 5.

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Time from onset of symptoms to recovery for COVID-19 patients.

Mean time from onset of symptoms to death

The estimated mean number of days from the onset of symptoms to death was reported in three studies with a pooled mean of 15.93 (95% CI: 13.07, 18.79). All of the studies were conducted in China (Fig. 6).

Fig. 6.

Fig. 6.

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Time from onset of symptoms to death for COVID-19.

Case fatality rate

The estimated CFR among COVID-19 patients was reported in 23 studies; most of which included hospitalised patients, three included ICU patients [37, 45, 60], and none included outpatients. The pooled CFR was estimated as 0.02 (95% CI: 0.02, 0.03) (Fig. 7). Heterogeneity testing (I2 = 97.6%) revealed notable differences among the included studies in the meta-analysis. Multivariate meta-regression results showed a significant difference in CFR by age (Adjusted β = 0.056; P-value = 0.003).

Fig. 7.

Fig. 7.

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Crude fatality rate among COVID-19 patients.

Discussion

We conducted a systematic review and meta-analysis to provide an overview of the epidemiological characteristics of COVID-19 based on the existing evidence as of 11 March 2020. Our findings suggest that COVID-19 has an average incubation period of 5.68 days and there is a lag of 4.92 days from onset of symptoms to the first clinical visit. On average, the symptoms of the patients lasted less than 20 days (18.55 days) before recovery was achieved and the CFR among confirmed COVID-19 patients was 2%, which significantly increased by age. Similar to previous studies [77], fever, dry cough, shortness of breath and fatigue were common symptoms among the patients in the included studies. As expected, history of direct or indirect exposure to Wuhan was frequently reported. The most common radiologic findings were bilateral consolidation and pneumonia [78, 79].

We found the average incubation period of COVID-19 infection to be less than 6 days which is broadly consistent with previously reported estimates [23, 29, 80, 81]. The right tail of the 99% CI of the incubation period for COVID-19 was less than 7 days (6.59). This finding is of particular interest as there are many uncertainties about the incubation period of COVID-19. For example, both the World Health Organization and Centers for Disease Control and Prevention in the USA suggest an incubation period of 2–14 days. However, single outlier cases as long as 19 [47], 24 [15] or 27 days [16] have been reported; estimates that are possibly reflecting a double exposure. Our findings are of particular importance for quarantine-related policies and planning and suggest that the current 14-day quarantine period might be rather conservative. Indeed, we found that except for one small study from China in Anyang city on a cluster of six patients [47], all other studies reported incubation periods less than 10.6 days; therefore, a shorter period of 14 days would suffice and almost all people exposed to SARS-CoV-2 would show symptoms within 11 days of their initial exposure. All in all, decisions to modify or keep the existing policies need to weigh the costs of extending active quarantine against the potential or costs of missing a few patients with delayed-onset symptoms.

COVID-19 seems to have a longer incubation period than that of other acute respiratory viral infections such as human coronavirus (3.2 days), influenza A (1.43–1.64 days), parainfluenza (2.6 days), respiratory syncytial virus (4.4 days) and rhinovirus (1.4 days) [82, 83]. Furthermore, the median incubation period for SARS has been estimated as 4.0 days in 2009 [82], which is considerably lower than what we observed for COVID-19. The longer incubation period of the COVID-19 may be one of the major factors that helps explain its rapid spread in comparison with previous respiratory infection viruses. Other factors contributing to the spread of COVID-19 are the lag between the onset of symptoms and first clinical visit (i.e. 4.92 days) and the high number of asymptomatic COVID-19 patients. These findings suggest that MERS and SARS patients may progress to severe symptoms and respiratory failures [84] much faster than most COVID-19 patients [85].

In comparison to MERS with a fatality rate of 35.67% [86] and SARS with a fatality rate of 11% [87], we found COVID-19 to have a much lower CFR (2%) that significantly increased by age (5.6% increase for every 10-year increase). Although this estimate is comparable with previous studies [40, 88], it is important to recognise the limitations of calculating fatality rates of COVID-19 while the epidemic is still growing. As most COVID-19 patients remain asymptomatic and may recover without seeking medical care, it is likely that the true CFR among people infected with SARS-CoV-2 could be even lower. On the other hand, the estimated fatality rates reported in most studies need to be interpreted with caution as they are often based on the cumulative number of deaths relative to the number of confirmed cases, while patients who die on a given day have been infected at a much earlier date and this would bias the denominator used to calculate the fatality rate [89].

We acknowledge four main limitations of our systematic review. First, our findings are mainly based on studies that recruited patient from clinics and hospitals and therefore, may be biased towards more severe cases. Moreover, our data might be skewed towards early reporting from provinces in China and outcomes might be different in other countries in the Western context. We are, therefore, aiming to update the review as more data become available in the next 12 months to provide more accurate estimates. Second, many studies did not report the study outcomes by subgroups such as age or sex and we could not report group-specific outcomes. Third, we used the mean and the standard error of the incubation period assuming a normal distribution which may have led to the underestimation of the right tail of the distribution. Lastly, given the urgency of the topic and the heterogeneity of the studies included in the review, we did not conduct the risk of bias or quality assessment of the studies. Given the emerging nature of COVID-19 and the observational study design of most of the available evidence, most studies in the review are at a high risk of bias and the quality of existing evidence is relatively low. Nonetheless, our systematic review of literature provides an insightful picture of the epidemiological characteristics of COVID-19 which could inform ongoing public health and public policy decision makings.

Conclusions

Our findings of the epidemiological characteristics of COVID-19 provide important insight into healthcare systems' prevention and planning efforts. The incubation period (i.e. <11 days in most studies) and the lag between the onset of symptoms and diagnosis (i.e. ~5 days) are longer for COVID-19 compared to other respiratory viral infections including MERS and SARS. Current policies of 14 days of mandatory quarantine for everyone potentially exposed to SARS-CoV-2 might be too conservative and longer quarantine periods might be more justified for extreme cases. As effective vaccination or treatment for COVID-19 are yet to be developed, practising the fundamentals of public health and prevention science such as physical distancing and personal hygiene are critical and need to be emphasised and enforced further to reduce the risk of SARS-CoV-2 transmission.

Acknowledgements

Authors did not receive any fund for this study. MK is a member of Pierre Elliott Trudeau Foundation's COVID-19 impact committee and is supported by the Vanier Canada Graduate Scholarship and the Pierre Elliott Trudeau Foundation Doctoral Scholarship.

Data availability statements

All of the data are presented in the paper. The dataset for meta-analysis is available upon reasonable request from the corresponding author (Hamid Sharifi; E-mail: hsharifi@kmu.ac.ir).

Supplementary material

For supplementary material accompanying this paper visit http://dx.doi.org/10.1017/S0950268820001430.

S0950268820001430sup001.docx (20.7KB, docx)

click here to view supplementary material

Conflict of interest

The authors declare no competing interests.

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Associated Data

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Supplementary Materials

For supplementary material accompanying this paper visit http://dx.doi.org/10.1017/S0950268820001430.

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Data Availability Statement

All of the data are presented in the paper. The dataset for meta-analysis is available upon reasonable request from the corresponding author (Hamid Sharifi; E-mail: hsharifi@kmu.ac.ir).

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