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Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22278300


BackgroundUptake of COVID-19 vaccination remains suboptimal in the United States and other settings. Though early reports indicated that a strong majority of people were interested in receiving the COVID-19 vaccine, the association between vaccine intention and uptake is not yet fully understood. MethodsDuring 24 February-5 December 2021, we enrolled California residents receiving molecular tests for SARS-CoV-2 infection who had not yet received any COVID-19 vaccine doses. Unvaccinated participants provided information on their intentions to receive COVID-19 vaccination in a telephone-administered survey. We matched study participants with a state-wide immunization registry and fit a Cox proportional hazards model comparing time to vaccination among those unvaccinated at study enrollment by vaccination intention (willing, unsure, or unwilling). FindingsAmong 864 participants who were unvaccinated at the time of interview, 272 (31%) had documentation of receipt of COVID-19 vaccination later; including 194/423 (45.9%) who had initially reported being willing to receive vaccination, 41/185 (22.2%) who reported being unsure about vaccination, and 37/278 (13.3%) who reported unwillingness to receive vaccination. Adjusted hazard ratios (aHRs) for registry-confirmed COVID-19 vaccination were 0.49 (95% confidence interval: 0.32-0.76) and 0.21 (0.12-0.36) for participants expressing uncertainty and unwillingness to receive vaccination, respectively, as compared with participants who reported being willing to receive vaccination. Time to vaccination was shorter among participants from higher-income households (aHR 3.30 [2.02-5.39]) and who reported co-morbidities or immunocompromising conditions (aHR 1.54 [1.01-2.36]); time to vaccination was longer among participants who tested positive for SARS-CoV-2 infection (aHR 0.60 [0.43-0.84]). Sensitivity of self-reported COVID-19 vaccination status was 82% (80-85%) overall, and 98% (97-99%) among those referencing vaccination records; specificity was 87% (86-89%). InterpretationParticipants stated willingness to receive COVID-19 vaccination was an imperfect predictor of real-world vaccine receipt. Improving messaging about the importance of COVID-19 vaccination, regardless of previous SARS-CoV-2 infection status, may improve vaccine uptake among populations who express hesitancy to initiate vaccination. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and medR{chi}iv for variations and combinations of the terms "vaccine hesitancy", "vaccine confidence", "vaccine uptake", "COVID-19", and "SARS-CoV-2" to identify original research articles published by March 8, 2022. The majority of screened articles were cross-sectional surveys conducted prior to or after implementation of COVID-19 vaccines to assess trends or predictors of participant-reported COVID-19 vaccine hesitancy. While some studies included random population-based samples, many were conducted within subgroups like health care professionals, parents of school aged children, or college students. Evidence about the association between COVID-19 vaccine intentions and subsequent vaccine uptake remains scarce. Three observational studies quantified associations between willingness to receive COVID-19 vaccination and subsequent initiation of vaccination; however, in these studies, follow-up time was limited to the period prior to widespread availability of COVID-19 vaccination or initiation of vaccine mandates in workplaces, schools, and other public places. Therefore, it was unclear whether remaining unvaccinated at follow-up in these studies was a choice or a consequence of the lack of universal access to COVID-19 vaccines. Additionally, most efforts to identify subsequent vaccine uptake relied on self-reported vaccination status, which may be subject to reporting or interviewer bias. We also searched PubMed and medR{chi}iv with variations and combinations of the terms "self-reported", "vaccination", "accuracy", and "COVID-19" and did not discover any articles validating self-reported COVID-19 vaccination status against immunization registry data; whereas, such studies were available for other vaccine-preventable pathogens including influenza, Streptococcus pneumoniae, and human papillomavirus. Added value of this studyWe linked data collected through an ongoing case-control study and a comprehensive state-wide immunization registry to evaluate the association between COVID-19 vaccination intention and subsequent uptake. We also assessed the reliability of self-reported COVID-19 vaccination status by linking participant records with a state-wide immunization registry. We are not aware of another published study assessing predictors of COVID-19 vaccine uptake spanning over 7 months of age-eligible follow-up time and adjudicating the use of self-reported COVID-19 vaccination status. We found that expressing hesitancy to receive COVID-19 vaccination was associated with lower adjusted hazards of subsequent vaccine uptake as compared with expressing willingness to receive vaccination (aHR: 0.49; 95% CI: 0.32-0.76), although uptake was also suboptimal among individuals who expressed willingness (45%). Participants from lower income households or who had recently tested positive for SARS-CoV-2 were slower to initiate vaccination than from higher income households or who had recently tested negative. People who were pregnant and initially deferred vaccination were faster to receive vaccination than participants who did not cite pregnancy as a reason for refusal. Upon assessing the accuracy of self-reported vaccination status, we found referencing a vaccination card or another calendar reference source improved sensitivity of self-reported vaccination status. Implications of all available evidenceWe provide an evaluation of predictors of COVID-19 vaccine uptake and assess the validity of self-reported COVID-19 vaccination status in comparison with a state-wide immunization registry. We identified that self-reported vaccination intent was a strong but imperfect predictor of subsequent vaccine initiation. However, no single reason for participants to express vaccine hesitancy predicted their likelihood of eventual vaccine receipt. As such, public health campaigns addressing multiple factors underlying vaccine hesitancy including those correcting sources of misinformation, and allaying concerns about short- or long-term side effects and vaccine safety remain important tools to improve acceptance in hesitant populations. Future studies reliant on the use of self-reported COVID-19 vaccination status should strive to utilize additional reference sources like COVID-19 vaccination cards or vaccination registries to reduce misclassification of vaccination status.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22275958


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.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21265295


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

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21262389


BackgroundWe examined school reopening policies amidst rising transmission of the highly transmissible Delta variant, accounting for vaccination among individuals aged 12 years and older, with the goal of characterizing risk to students and teachers under various within-school non-pharmaceutical interventions (NPIs) combined with specific vaccination coverage levels. MethodsWe developed an individual-based transmission model to simulate transmission of the Delta variant of SARS-CoV-2 among a synthetic population, representative of Bay Area cities. We parameterized the model using community contact rates from vaccinated households ascertained from a household survey of Bay Area families with children conducted between February - April, 2021. Interventions and outcomesWe evaluated the additional infections in students and teachers/staff resulting over a 128-day semester from in-school instruction compared to remote instruction when various NPIs (mask use, cohorts, and weekly testing of students/teachers) were implemented in schools, across various community-wide vaccination coverages (50%, 60%, 70%), and student ([≥]12 years) and teacher/staff vaccination coverages (50% - 95%). We quantified the added benefit of universal masking over masking among unvaccinated students and teachers, across varying levels of vaccine effectiveness (45%, 65%, 85%), and compared results between Delta and Alpha variant circulation. ResultsThe Delta variant sharply increases the risk of within-school COVID-transmission when compared to the Alpha variant. In our highest risk scenario (50% community and within-school vaccine coverage, no within-school NPIs, and predominant circulation of the Delta variant), we estimated that an elementary school could see 33-65 additional symptomatic cases of COVID-19 over a four-month semester (depending on the relative susceptibility of children <10 years). In contrast, under the Bay Area reopening plan (universal mask use, community and school vaccination coverage of 70%), we estimated excess symptomatic infection attributable to school reopening among 2.0-9.7% of elementary students (8-36 excess symptomatic cases per school over the semester), 3.0% of middle school students (13 cases per school) and 0.4% of high school students (3 cases per school). Excess rates among teachers attributable to reopening were similar. Achievement of lower risk tolerances, such as <5 excess infections per 1,000 students or teachers, required a cohort approach in elementary and middle school populations. In the absence of NPIs, increasing the vaccination coverage of community members from 50% to 70% or elementary teachers from 70% to 95% reduced the estimated excess rate of infection among elementary school students attributable to school transmission by 24% and 41%, respectively. We estimated that with 70% coverage of the eligible community and school population with a vaccine that is [≤]65% effective, universal masking can avert more cases than masking of unvaccinated persons alone. ConclusionsAmidst circulation of the Delta variant, our findings demonstrated that schools are not inherently low risk, yet can be made so with high community vaccination coverages and universal masking. Vaccination of adult community members and teachers protects unvaccinated elementary and middle school children. Elementary and middle schools that can support additional interventions, such as cohorts and testing, should consider doing so, particularly if additional studies find that younger children are equally as susceptible as adults to the Delta variant of SARS-CoV-2. LimitationsWe did not consider the effect of social distancing in classrooms, or variation in testing frequency, and considerable uncertainty remains in key transmission parameters.

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