Meta-analysis of the severe acute respiratory syndrome coronavirus 2 serial intervals and the impact of parameter uncertainty on the coronavirus disease 2019 reproduction number

• Published in: Statistical methods in medical research Vol. 31; no. 9; pp. 1686 - 1703
• Main Authors: Challen, Robert, Brooks-Pollock, Ellen, Tsaneva-Atanasova, Krasimira, Danon, Leon
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.09.2022; Sage Publications Ltd
• Subjects: Contact tracing; Coronaviruses; COVID-19; COVID-19 - epidemiology; Disease Outbreaks; Disease transmission; Empirical analysis; Estimates; Estimation; Hospitalization; Humans; Infections; Infectious diseases; Mathematical models; Meta-analysis; Normal distribution; Parameter uncertainty; Probability distribution functions; Reproduction; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Special Issue; Statistical analysis; Uncertainty; Viral diseases; Severe acute respiratory syndrome coronavirus 2; generation interval; serial interval; coronavirus disease 2019; incubation period
• ISSN: 0962-2802; 1477-0334; 1477-0334
• DOI: 10.1177/09622802211065159

The serial interval of an infectious disease, commonly interpreted as the time between the onset of symptoms in sequentially infected individuals within a chain of transmission, is a key epidemiological quantity involved in estimating the reproduction number. The serial interval is closely related to other key quantities, including the incubation period, the generation interval (the time between sequential infections), and time delays between infection and the observations associated with monitoring an outbreak such as confirmed cases, hospital admissions, and deaths. Estimates of these quantities are often based on small data sets from early contact tracing and are subject to considerable uncertainty, which is especially true for early coronavirus disease 2019 data. In this paper, we estimate these key quantities in the context of coronavirus disease 2019 for the UK, including a meta-analysis of early estimates of the serial interval. We estimate distributions for the serial interval with a mean of 5.9 (95% CI 5.2; 6.7) and SD 4.1 (95% CI 3.8; 4.7) days (empirical distribution), the generation interval with a mean of 4.9 (95% CI 4.2; 5.5) and SD 2.0 (95% CI 0.5; 3.2) days (fitted gamma distribution), and the incubation period with a mean 5.2 (95% CI 4.9; 5.5) and SD 5.5 (95% CI 5.1; 5.9) days (fitted log-normal distribution). We quantify the impact of the uncertainty surrounding the serial interval, generation interval, incubation period, and time delays, on the subsequent estimation of the reproduction number, when pragmatic and more formal approaches are taken. These estimates place empirical bounds on the estimates of most relevant model parameters and are expected to contribute to modeling coronavirus disease 2019 transmission.