Waning of 2-Dose BNT162b2 and mRNA-1273 Vaccine Effectiveness Against Symptomatic SARS-CoV-2 Infection Accounting for Depletion-of-Susceptibles Bias.

Concerns about the duration of protection conferred by coronavirus disease 2019 (COVID-19) vaccines have arisen in postlicensure evaluations. "Depletion of susceptibles," a bias driven by differential accrual of infection among vaccinated and unvaccinated individuals, may obscure vaccine effectiveness (VE) estimates, hindering interpretation. 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 February 23 and December 5, 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from a population-based serological study to adjust for "depletion-of-susceptibles" bias and estimated VE for 3 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 (CI): 83.8, 95.4) at 14 days after second-dose receipt and declined to 50.8% (95% CI: 19.7, 69.8) at 7 months. Adjusting for depletion-of-susceptibles bias, we estimated VE of 53.2% (95% CI: 23.6, 71.2) at 7 months after primary mRNA vaccination series. A booster dose of BN162b2 or mRNA-1273 increased VE to 95.0% (95% CI: 82.8, 98.6). 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.

Predictors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following High-Risk Exposure.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. METHODS: We 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-12 November, 2021. We used conditional logistic regression to estimate adjusted odds ratios (aORs) 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") ≤14 days before testing. RESULTS: 751 of 1448 cases (52%) and 255 of 1443 controls (18%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 3.02-fold (95% confidence interval: 1.75-5.22) higher when high-risk exposures occurred with household members (vs. other contacts), 2.10-fold (1.05-4.21) higher when exposures occurred indoors (vs. outdoors only), and 2.15-fold (1.27-3.67) 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. Cases were less likely than controls to report mask usage during high-risk exposures (aOR = 0.50 [0.29-0.85]). The adjusted odds of case status was lower for fully-vaccinated (aOR = 0.25 [0.15-0.43]) participants compared to unvaccinated participants. Benefits of mask usage were greatest among unvaccinated and partially-vaccinated participants, and in interactions involving non-household contacts or interactions occurring without physical contact. CONCLUSIONS: NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.

Effectiveness of Face Mask or Respirator Use in Indoor Public Settings for Prevention of SARS-CoV-2 Infection - California, February-December 2021.

The use of face masks or respirators (N95/KN95) is recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Well-fitting face masks and respirators effectively filter virus-sized particles in laboratory conditions (2,3), though few studies have assessed their real-world effectiveness in preventing acquisition of SARS-CoV-2 infection (4). A test-negative design case-control study enrolled randomly selected California residents who had received a test result for SARS-CoV-2 during February 18-December 1, 2021. Face mask or respirator use was assessed among 652 case-participants (residents who had received positive test results for SARS-CoV-2) and 1,176 matched control-participants (residents who had received negative test results for SARS-CoV-2) who self-reported being in indoor public settings during the 2 weeks preceding testing and who reported no known contact with anyone with confirmed or suspected SARS-CoV-2 infection during this time. Always using a face mask or respirator in indoor public settings was associated with lower adjusted odds of a positive test result compared with never wearing a face mask or respirator in these settings (adjusted odds ratio [aOR] = 0.44; 95% CI = 0.24-0.82). Among 534 participants who specified the type of face covering they typically used, wearing N95/KN95 respirators (aOR = 0.17; 95% CI = 0.05-0.64) or surgical masks (aOR = 0.34; 95% CI = 0.13-0.90) was associated with significantly lower adjusted odds of a positive test result compared with not wearing any face mask or respirator. These findings reinforce that in addition to being up to date with recommended COVID-19 vaccinations, consistently wearing a face mask or respirator in indoor public settings reduces the risk of acquiring SARS-CoV-2 infection. Using a respirator offers the highest level of personal protection against acquiring infection, although it is most important to wear a mask or respirator that is comfortable and can be used consistently.

Mixed methods approach to examining the implementation experience of a phone-based survey for a SARS-CoV-2 test-negative case-control study in California.

OBJECTIVE: To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. STUDY DESIGN: Test-negative case-control study. METHODS: Between February 24, 2021 - February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. RESULTS: Cases had 1.29-fold (95% CI: 1.24-1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56-1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. CONCLUSIONS: Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic.