ABSTRACT
Concerns about the duration of protection conferred by COVID-19 vaccines have arisen in postlicensure evaluations. However, "depletion of susceptibles" bias driven by differential accrual of infection among vaccinated and unvaccinated individuals may contribute to the appearance of waning vaccine effectiveness (VE) in epidemiologic studies, potentially hindering interpretation of estimates. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design case-control study to estimate VE of mRNA-based COVID-19 vaccines between 23 February and 5 December 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from case-based surveillance along with estimated case-to-infection ratios from a population-based serological study to quantify the potential contribution of the "depletion-of-susceptibles" bias to time-varying VE estimates for 2 doses. We also estimated VE for 3 doses relative to 0 doses and 2 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval: 83.8-95.4%) at 14 days after second-dose receipt and declined to 50.8% (31.2-75.6%) at 7 months. Accounting for differential depletion-of-susceptibles among vaccinated and unvaccinated individuals, we estimated VE was 53.2% (23.6-71.2%) at 7 months among individuals who had completed the primary series (2 doses). With receipt of a third dose of BN162b2 or mRNA-1273, VE increased to 95.0% (82.8-98.6%), compared with zero doses. These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.
ABSTRACT
BackgroundNon-pharmaceutical interventions (NPIs) are recommended for COVID-19 mitigation. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. MethodsWe conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-26 September, 2021. We used conditional logistic regression to assess predictors of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 ("high-risk exposure") within [≤]14 days of testing. Results643 of 1280 cases (50.2%) and 204 of 1263 controls (16.2%) reported high-risk exposures [≤]14 days before testing. Adjusted odds of case status were 2.94-fold (95% confidence interval: 1.66-5.25) higher when high-risk exposures occurred with household members (vs. other contacts), 2.06-fold (1.03-4.21) higher when exposures occurred indoors (vs. not indoors), and 2.58-fold (1.50-4.49) higher when exposures lasted [≥]3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Mask usage by participants or their contacts during high-risk exposures reduced adjusted odds of case status by 48% (8-72%). Adjusted odds of case status were 68% (32-84%) and 77% (59-87%) lower for partially- and fully-vaccinated participants, respectively, than for unvaccinated participants. Benefits of mask usage were greatest when exposures lasted [≥]3 hours, occurred indoors, or involved non-household contacts. ConclusionsNPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons. KEY POINTSO_LISARS-CoV-2 infection risk was greatest for unvaccinated participants when exposures to known or suspected cases occurred indoors or lasted [≥]3 hours. C_LIO_LIFace mask usage when participants were exposed to a known or suspect case reduced odds of infection by 48%. C_LI
