Objectives The aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19. Design Rapid systematic review and meta-analysis of observational research. Setting International studies on incubation period of COVID-19. Participants Searches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies. Primary outcome measures Parameters of a lognormal distribution of incubation periods. Results The incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days. Conclusions The choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.

https://bmjopen.bmj.com/content/bmjopen/10/8/e039652.full.pdf

Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research.

BACKGROUND: Asymptomatic infection seems to be a notable feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), but the prevalence is uncertain. PURPOSE: To estimate the proportion of persons infected with SARS-CoV-2 who never develop symptoms. DATA SOURCES: Searches of Google News, Google Scholar, medRxiv, and PubMed using the keywords antibodies, asymptomatic, coronavirus, COVID-19, PCR, seroprevalence, and SARS-CoV-2. STUDY SELECTION: Observational, descriptive studies and reports of mass screening for SARS-CoV-2 that were either cross-sectional or longitudinal in design; were published through 17 November 2020; and involved SARS-CoV-2 nucleic acid or antibody testing of a target population, regardless of current symptomatic status, over a defined period. DATA EXTRACTION: The authors collaboratively extracted data on the study design, type of testing performed, number of participants, criteria for determining symptomatic status, testing results, and setting. DATA SYNTHESIS: Sixty-one eligible studies and reports were identified, of which 43 used polymerase chain reaction (PCR) testing of nasopharyngeal swabs to detect current SARS-CoV-2 infection and 18 used antibody testing to detect current or prior infection. In the 14 studies with longitudinal data that reported information on the evolution of symptomatic status, nearly three quarters of persons who tested positive but had no symptoms at the time of testing remained asymptomatic. The highest-quality evidence comes from nationwide, representative serosurveys of England (n = 365 104) and Spain (n = 61 075), which suggest that at least one third of SARS-CoV-2 infections are asymptomatic. LIMITATION: For PCR-based studies, data are limited to distinguish presymptomatic from asymptomatic infection. Heterogeneity precluded formal quantitative syntheses. CONCLUSION: Available data suggest that at least one third of SARS-CoV-2 infections are asymptomatic. Longitudinal studies suggest that nearly three quarters of persons who receive a positive PCR test result but have no symptoms at the time of testing will remain asymptomatic. Control strategies for COVID-19 should be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Proportion of SARS-CoV-2 Infections That Are Asymptomatic : A Systematic Review.

Objectives Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach. Design Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics. Information sources Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases. Results There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5–9.5 days. Median presymptomatic infectious period across studies varied over Conclusions There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.

https://bmjopen.bmj.com/content/bmjopen/10/8/e039856.full.pdf

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases.

Studies of novel coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have reported varying estimates of epidemiological parameters, including serial interval distributions-i.e., the time between illness onset in successive cases in a transmission chain-and reproduction numbers. By compiling a line-list database of transmission pairs in mainland China, we show that mean serial intervals of COVID-19 shortened substantially from 7.8 to 2.6 days within a month (9 January to 13 February 2020). This change was driven by enhanced nonpharmaceutical interventions, particularly case isolation. We also show that using real-time estimation of serial intervals allowing for variation over time provides more accurate estimates of reproduction numbers than using conventionally fixed serial interval distributions. These findings could improve our ability to assess transmission dynamics, forecast future incidence, and estimate the impact of control measures.

/pdf/serial-interval-of-sars-cov-2-was-shortened-over-time-by-3htsth1obo.pdf

Serial interval of SARS-CoV-2 was shortened over time by nonpharmaceutical interventions.

Key Points Question What are the incubation periods of COVID-19 caused by different SARS-CoV-2 strains? Findings In this systematic review and meta-analysis of 141 articles, the pooled incubation period was 6.57 days. The incubation periods of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were 5.00, 4.50, 4.41, and 3.42 days, respectively. Meaning These results suggest that with the evolution of mutant strains, the incubation period of COVID-19 decreased gradually from Alpha variant to Omicron variant.

/pdf/incubation-period-of-covid-19-caused-by-unique-sars-cov-2-1av66u9m.pdf

Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains

Background
The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between exposure of infector and infectee), serial interval, time point of exposure and basic reproduction number (R0) of COVID-19.
Methods
Between late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented.
Findings
In total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and -0.19 day (i.e., 0.19 day before symptom onset of infector) and 3.32 days for time point of exposure. R0 was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before the symptom onsets of infectors. In 27 (3.92%) infector-infectee pairs, symptom onsets of infectees occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed.
Interpretation
This study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures.

/pdf/epidemiological-parameters-of-coronavirus-disease-2019-a-1fljul1ya3.pdf

Epidemiological parameters of coronavirus disease 2019: a pooled analysis of publicly reported individual data of 1155 cases from seven countries

Estimating the generation interval and inferring the latent period of COVID-19 from the contact tracing data.

Background: The estimates of several key epidemiological parameters of the COVID-19 pandemic are often based on small sample sizes or are inaccurate for various reasons.
Objective: The aim of this study is to obtain more robust estimates of the incubation period, serial interval, frequency of presymptomatic transmission, and basic reproduction number (R0) of COVID-19 based on a large case series.
Methods: We systematically retrieved and screened 20,658 reports of laboratory-confirmed COVID-19 cases released by the health authorities of China, Japan, and Singapore. In addition, 9942 publications were retrieved from PubMed and China National Knowledge Infrastructure (CNKI) through April 8, 2020. To be eligible, a report had to contain individual data that allowed for accurate estimation of at least one parameter. Widely used models such as gamma distributions were fitted to the data sets and the results with the best-fitting values were presented.
Results: In total, 1591 cases were included for the final analysis. The mean incubation period (n=687) and mean serial interval (n=1015 pairs) were estimated to be 7.04 (SD 4.27) days and 6.49 (SD 4.90) days, respectively. In 40 cases (5.82%), the incubation period was longer than 14 days. In 32 infector-infectee pairs (3.15%), infectees’ symptom onsets occurred before those of infectors. Presymptomatic transmission occurred in 129 of 296 infector-infectee pairs (43.58%). R0 was estimated to be 1.85 (95% CI 1.37-2.60).
Conclusions: This study provides robust estimates of several epidemiological parameters of COVID-19. The findings support the current practice of 14-day quarantine of persons with potential exposure, but also suggest the need for additional measures. Presymptomatic transmission together with the asymptomatic transmission reported by previous studies highlight the importance of adequate testing, strict quarantine, and social distancing.

/pdf/epidemiological-parameters-of-covid-19-case-series-study-3nnivxxmt5.pdf

Epidemiological Parameters of COVID-19: Case Series Study.

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Epidemiological parameters of coronavirus disease 2019: a pooled analysis of publicly reported individual data of 1155 cases from seven countries

Estimating the generation interval and inferring the latent period of COVID-19 from the contact tracing data.

Epidemiological Parameters of COVID-19: Case Series Study.