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 280 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, although we did not find statistically significant differences between the Omicron subvariants. We found that Omicron BA.1 had the shortest pooled estimates for the incubation period (3.49 days, 95% CI: 3.13-4.86 days), Omicron BA.5 for the serial interval (2.37 days, 95% CI: 1.71-3.04 days), and Omicron BA.1 for the realized generation time (2.99 days, 95% CI: 2.48-3.49 days). Only one estimate for the intrinsic generation time was available for Omicron subvariants: 6.84 days (95% CrI: 5.72-8.60 days) for Omicron BA.1. The ancestral lineage had the highest pooled estimates for each investigated key time-to-event period. We also observed shorter pooled estimates for the serial interval compared to the incubation period across the virus lineages. When pooling the estimates across different virus lineages, we found considerable heterogeneities (I² > 80%; I² refers to the percentage of total variation across studies that is due to heterogeneity rather than chance), possibly resulting from heterogeneities between the different study populations (e.g., deployed interventions, social behavior, demographic characteristics).

Conclusions: 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; Incubation period; Intrinsic generation time; Meta-analysis; Realized generation time; Serial interval; Systematic review; Variants of concern.

Fig. 1

Illustrative example of individual observations of the incubation period, serial interval, and generation time. The top part of the figure shows two hypothetical transmission chains as well as the dates of infection and symptom onset (if any) of infected individuals. Each row corresponds to a study participant (#1–#6). The bottom part of the figure shows the estimated individual values of the incubation period, serial interval, and generation time

Fig. 2

Study flow diagram

Fig. 3

The reported estimates of the incubation period. The blue vertical dotted line and rectangle correspond to the pooled mean estimate and its 95% CI of the ancestral lineage, respectively. The red vertical dotted line and rectangle in different strata denote the pooled mean estimates and their 95% CI of corresponding variants, respectively. Black points and triangles represent mean estimates and median estimates, respectively. The horizontal segments indicate CI (green), CrI (light blue), IQR (yellow), and range (orange)

Fig. 4

The reported estimates of the serial interval. The blue vertical dotted line and rectangle correspond to the pooled mean estimate and its 95% CI of the ancestral lineage, respectively. The red vertical dotted line and rectangle in different strata denote the pooled mean estimates and their 95% CI of corresponding variants, respectively. Black points and triangles represent mean estimates and median estimates, respectively. The horizontal segments indicate CI (green), CrI (light blue), and IQR (yellow)

Fig. 5

The reported estimates of the realized generation time. The blue vertical dotted line and rectangle correspond to the pooled mean estimate and its 95% CI of the ancestral lineage, respectively. The red vertical dotted line and rectangle in different strata denote the pooled mean estimates and their 95% CI of corresponding variants, respectively. Black points and triangles represent mean estimates and median estimates, respectively. The horizontal segments indicate CI (green) and CrI (light blue)

Fig. 6

The reported estimates of the intrinsic generation time. The red vertical dotted line and rectangle in different strata denote the pooled mean estimates and their 95% CI of corresponding variants, respectively. Black points and triangles represent mean estimates and median estimates, respectively. The horizontal segments indicate CrI (light blue)