Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases including SARS-CoV-2. However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2-4.2 fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.

Background Dose fractionation of a coronavirus disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are unavailable, especially with emerging variants. Methods We systematically reviewed clinical trials that reported dose-finding results and estimated the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines using a generalized additive model. We predicted the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared seroconversion to nAbs, T cell responses, and safety profiles between fractional and standard dose groups. Results We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2-specific nAbs and T cells that confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants up to Omicron. Safety profiles of fractional doses were non-inferior to the standard dose. Conclusions Dose fractionation of mRNA and protein subunit vaccines may be safe and effective, which would also vary depending on the characteristics of emerging variants and updated vaccine formulations.

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases (including SARS-CoV-2). However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2-4.2 fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management.One Sentence SummaryIn this study, variation of individual infectiousness is quantified. Potential sources of such variation, particularly heterogeneity of viral shedding is discussed.

Background Accurate estimation of household secondary attack rate (SAR) is crucial to understand the transmissibility of SARS-CoV-2. The impact of population-level factors, such as transmission intensity in the community on SAR estimates are however rarely explored. Methods In this study, we included articles with original data to compute the household SAR. To determine the impact of transmission intensity in the community on household SAR estimates, we explored the association between SAR estimates and the incidence rate of cases by country during the study period. Results We identified 163 studies to extract data on SARs from 326,031 cases and 2,009,859 household contacts. The correlation between incidence rate of cases during the study period and SAR estimates was 0.37 (95% CI: 0.24-0.49). We found that doubling incidence rate of cases during the study period was associated with a 1.2% (95% CI: 0.5%, 1.8%) higher household SAR. Conclusions Our findings suggest that the incidence rate of cases during the study period is associated with higher SAR. Ignoring this factor may overestimate SARs, especially for regions with high incidences, which further impacts control policies and epidemiological characterization of emerging variants.