Assessing changes in incubation period, serial interval, and generation time of SARS-CoV-2 variants of concern: a systematic review and meta-analysis

Abstract

Background: After the first COVID-19 wave caused by the ancestral lineage, the pandemic has been fueled from the continuous emergence of new SARS-CoV-2 variants. Understanding key time-to-event periods for each emerging variant of concern is critical as it can provide insights into the future trajectory of the virus and help inform outbreak preparedness and response planning. Here, we aim to examine how the incubation period, serial interval, and generation time have changed from the ancestral SARS-CoV-2 lineage to different variants of concern. Methods: We conducted a systematic review and meta-analysis that synthesized the estimates of incubation period, serial interval, and generation time (both realized and intrinsic) for the ancestral lineage, Alpha, Beta, and Omicron variants of SARS-CoV-2. Results: Our study included 274 records obtained from 147 household studies, contact tracing studies or studies where epidemiological links were known. With each emerging variant, we found a progressive shortening of each of the analyzed key time-to-event periods. Specifically, we found that Omicron had the shortest pooled estimates for the incubation period (3.63 days, 95%CI: 3.25-4.02 days), serial interval (3.19 days, 95%CI: 2.95-3.43 days), and realized generation time (2.96 days, 95%CI: 2.54-3.38 days) whereas the ancestral lineage had the highest pooled estimates for each of them. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. We found considerable heterogeneities (I2 > 80%) when pooling the estimates across different virus lineages, indicating potential unmeasured confounding from population factors (e.g., social behavior, deployed interventions). Conclusion: Our study supports the importance of conducting contact tracing and epidemiological investigations to monitor changes in SARS-CoV-2 transmission patterns. Our findings highlight a progressive shortening of the incubation period, serial interval, and generation time, which can lead to epidemics that spread faster, with larger peak incidence, and harder to control. We also consistently found a shorter serial interval than incubation period, suggesting that a key feature of SARS-CoV-2 is the potential for pre-symptomatic transmission. These observations are instrumental to plan for future COVID-19 waves. Keywords: COVID-19, variants of concern, incubation period, serial interval, realized generation time, intrinsic generation time, systematic review, meta-analysis

Investigation of the Molecular Epidemiology and Evolution of Circulating Severe Acute Respiratory Syndrome Coronavirus 2 in Thailand from 2020 to 2022 via Next-Generation Sequencing

“…A previous study examined the global evolution rate of SARS-CoV-2 during the early stages of the outbreak and reported an estimated mean nucleotide mutation rate ranging from 1.79 × 10 −3 to 1.83 × 10 −3 substitutions per site per year [ 29 ]. In another study, it was suggested that the incubation period, serial interval, and generation time of SARS-CoV-2 have progressively decreased with the emergence of each new VOC [ 30 ].…”