Relative infectiousness of SARS-CoV-2 vaccine breakthrough infections, reinfections, and primary infections

Abstract

SARS-CoV-2 breakthrough infections in vaccinated individuals and in those who had a prior infection have been observed globally, but the transmission potential of these infections is unknown. The RT-qPCR cycle threshold (Ct) value is inversely correlated with viral load and culturable virus. Here, we investigate differences in RT-qPCR Ct values across Qatar's national cohorts of primary infections, reinfections, BNT162b2 (Pfizer-BioNTech) breakthrough infections, and mRNA-1273 (Moderna) breakthrough infections. Our matched-cohort analyses of the randomly diagnosed infections show higher mean Ct value in all cohorts of breakthrough infections compared to the cohort of primary infections in unvaccinated individuals. The Ct value is 1.3 (95% CI: 0.9-1.8) cycles higher for BNT162b2 breakthrough infections, 3.2 (95% CI: 1.9-4.5) cycles higher for mRNA-1273 breakthrough infections, and 4.0 (95% CI: 3.5-4.5) cycles higher for reinfections in unvaccinated individuals. Since Ct value correlates inversely with SARS-CoV-2 infectiousness, these differences imply that vaccine breakthrough infections and reinfections are less infectious than primary infections in unvaccinated individuals. Public health benefits of vaccination may have been underestimated, as COVID-19 vaccines not only protect against acquisition of infection, but also appear to protect against transmission of infection.

Fig. 1. Flowchart illustrating the population selection process.

Flowchart illustrating the selection of the cohorts of (a) primary infections in unvaccinated individuals, (b) reinfections in unvaccinated individuals, (c) BNT162b2-vaccine breakthrough infections, and (d) mRNA-1273-vaccine breakthrough infections.

Fig. 2. Schematic diagram showing the process of formulating the six pairwise comparisons between study cohorts.

Schematic diagram showing the process of formulating the six pairwise comparisons between the cohorts of primary infections in unvaccinated individuals, reinfections in unvaccinated individuals, BNT162b2-vaccine breakthrough infections, and mRNA-1273-vaccine breakthrough infections, after 1:1 matching by sex, 10-year age group, reason for RT-qPCR testing, and calendar week of the RT-qPCR test.

Fig. 3. RT-qPCR Ct values in the randomly diagnosed (asymptomatic) SARS-CoV-2 infections.

Distribution of these Ct values (blue circles) in the six pairwise comparisons between primary infections in unvaccinated individuals, reinfections in unvaccinated individuals, BNT162b2-vaccine breakthrough infections, and mRNA-1273-vaccine breakthrough infections, a–f. A randomly diagnosed infection was defined as an RT-qPCR-positive test conducted with no prior reason to suspect infection and no reported presence of symptoms compatible with a respiratory tract infection. That is, the RT-qPCR test was conducted as part of a survey (random testing campaigns), for routine healthcare testing, for pre-travel requirement, or at port of entry upon arrival in Qatar. a includes, in each comparison group, n = 1584 biologically independent samples, b includes n = 158 biologically independent samples, c includes n = 140 biologically independent samples, d includes n = 987 biologically independent samples, e includes n = 421 biologically independent samples, and f includes n = 60 biologically independent samples, each over 1 experiment. Boxplots center lines indicate the median Ct values, box limits indicate the 25% and 75% quartiles, and whiskers indicate maximum and minimum observations within 1.5 of interquartile range. Paired t tests were used to compare the difference in means between study groups, with no adjustment for multiple comparisons. Two-sided p-values are reported.