Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection

Abstract

The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts' socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.

Fig. 1. Adjusted secondary attack rate.

Estimated Adjusted Secondary Attack Rate (diamond) and its 95% confidence interval (error bars) stratified per variant (EU, alpha, delta and omicron), with the reference value indicated with a vertical line (reference of each covariate is indicated in bold in parenthesis). Estimates and confidence intervals are produced by a generalized estimating equations linear regression with robust standard errors predicting a binary outcome indicating if the contact was infected by the index or not, using the index cases as cluster and an exchangeable correlation structure. The estimates are based on 42,295 index-contact relations for the EU variant, 20,311 for the alpha variant, 27,260 for the delta variant and 21,808 for the omicron variant. Estimates are adjusted for the index case gender, age, obesity, presence of symptoms, presence of cough, immunity status, neighbourhood socioeconomic condition, vulnerability and type of living; the link between the index case and its contacts, and for the contact persons, their gender, age, number of tests performed the three months before the contact date with the index case, and their immunity status. The reference index case–contact relation of this multivariate analysis is the contact between two men of age below 65 living at the same place, the index being not vaccinated not infected (NVNI), not obese, living in a wealthy neighbourhood and being not a vulnerable person, living in a housing building, and the contact person being a NVNI adult men who performed one SARS-CoV-2 test during the last 3 month preceding the contact. Exact values of the estimated can be found in Table 2, and unadjusted estimates are presented in supplementary table S4.

Fig. 2. Immunity, susceptibility to be infected and infectiousness.

Effect of immunity (recent vaccination, recent infection or hybrid immunity) on the susceptibility to be infected (magenta) or on the infectiousness (yellow), expressed as the estimated percent point change of secondary attack rate (circle) and its 95% confidence interval (error bars), stratified per period of variant predominance. Estimates and confidence intervals are produced by a generalized estimating equations linear regression with robust standard errors predicting a binary outcome indicating if the contact was infected by the index or not, using the index cases as cluster and an exchangeable correlation structure. Estimates are adjusted for the index case gender, age, obesity, presence of symptoms, presence of cough, immunity status, neighbourhood socioeconomic condition, vulnerability and type of living; the link between the index case and its contacts, and for the contact persons, their gender, age, number of tests performed the three months before the contact date with the index case, their immunity status, and an interaction between immunity status and number of tests performed. The reference index case–contact relation of this multivariate analysis is the contact between two men of age below 65 living at the same place, the index being not vaccinated not infected (NVNI), not obese, living in a wealthy neighbourhood and being not a vulnerable person, living in a housing building, and the contact person being a NVNI adult men who performed one SARS-CoV-2 test during the last 3 month preceding the contact. Same results are presented graphically in Fig. 1.