key: cord-0871257-aoytgxy6
authors: Andrejko, K.; Pry, J. M.; Myers, J. F.; Jewell, N. P.; Openshaw, J.; Watt, J.; Jain, S.; Lewnard, J. A.
title: Early evidence of COVID-19 vaccine effectiveness within the general population of California
date: 2021-04-10
journal: nan
DOI: 10.1101/2021.04.08.21255135
sha: 39a7ad40273ea1fa56df71d7f54f2e0db5b8c329
doc_id: 871257
cord_uid: aoytgxy6

Importance: Evidence is needed to determine COVID-19 vaccine effectiveness under real world conditions of use. Objective: To determine the effectiveness of authorized vaccines against COVID-19 in the context of substantial circulation of SARS-CoV-2 variants of concern, and identify vaccine uptake barriers. Design: We recruited cases (testing positive) and controls (testing negative) based on SARS-CoV-2 molecular diagnostic test results from 24 February-7 April 2021. Controls were individually matched to cases by age, sex, and geographic region. We identified cases and controls via random sampling within predetermined demographic strata. We conducted enrollment and administered study questionnaires via telephone-based facilitated interviews. Setting: Population-based surveillance of all SARS-CoV-2 molecular diagnostic testing reported to the California Department of Public Health. During the study period, 69% of sequenced SARS-CoV-2 isolates in California belonged to variants of concern B.1.1.7, B.1.427, or B.1.429. Participants: We enrolled 645 adults aged [≥]18y, including 325 cases and 320 controls Exposures: We assessed participants' self-reported history of COVID-19 vaccine receipt (BNT162b2 and mRNA-1273). Individuals were considered fully vaccinated two weeks after second dose receipt. Main Outcomes and Measures: The primary endpoint was a positive SARS-CoV-2 molecular test result. For unvaccinated participants, we assessed willingness to receive vaccination, when eligible. We measured vaccine effectiveness via the matched odds ratio of prior vaccination, comparing cases with controls. Results: Among 325 cases, 23 (7%) and 13 (4%) received BNT162b2 and mRNA-1273, respectively; 8 (2%) were fully vaccinated with either product. Among 260 controls, 49 (19%) and 49 (19%) received BNT162b2 and mRNA-1273, respectively; 42 (16%) were fully vaccinated with either product. Among fully vaccinated individuals, vaccine effectiveness was 86% (95% confidence interval: 67-94%). Vaccine effectiveness was 66% (-69% to 93%) and 78% (23% to 94%) one week following a first and second dose, respectively. Among unvaccinated participants, 39% of those residing in rural regions and 23% of those residing in urban regions reported hesitancy to receive COVID-19 vaccines, when eligible. In contrast, vaccine hesitancy did not significantly differ by age, sex, household income, or race/ethnicity. Conclusions and Relevance: Ongoing vaccination efforts are preventing SARS-CoV-2 infection in the general population in California. Vaccine hesitancy presents a barrier to reaching coverage levels needed for herd immunity.

Following demonstrations of efficacy in preventing coronavirus disease 2019 in randomized controlled trials, 1-3 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being administered to the general public. Two mRNA-based vaccines encoding the SARS-CoV-2 spike protein, BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), have been used since December 2020, and were administered to 24% of California residents by early April 2021. 4 Observational studies characterizing COVID-19 vaccine effectiveness (VE) are needed to understand performance under real-world conditions and to inform implementation programs. 5 Such studies allow VE assessment against alternative clinical endpoints, as novel SARS-CoV-2 variants emerge and circulate, and under dosing schedules that differ from those assessed in randomized trials. 6 To date, most studies of real-world VE have enrolled healthcare workers and other essential or frontline personnel, and have been undertaken in settings without substantial circulation of SARS-CoV-2 variants of concern. However, as of March, 2021, variants B.1.1.7, B.1.427, and B.1.429 accounted for 69% of all sequenced SARS-CoV-2 isolates in California. 7 In conjunction with epidemiologic surveillance, we initiated a test-negative design case-control study to monitor VE within the general population of California. Here we provide an early assessment of VE for authorized mRNA-based COVID-19 vaccines based on experience with implementation within the general population. Additionally, to inform future vaccination strategies, we assessed the intention of unvaccinated participants to receive vaccination once eligible.

All diagnostic tests in California for SARS-CoV-2 infection are reported by laboratories and medical providers to their local health jurisdiction (LHJ). Sixty of 61 LHJs report data directly to the California Department of Public Health (CDPH) via a web-based reporting system, while Los Angeles County transmits data daily via an electronic file. California residents receiving molecular SARS-CoV-2 tests with results posted between 24 February-7 April, 2021 were eligible for participation in this study. Cases were individuals with positive molecular test results for SARS-CoV-2 infection, reported over the study timeframe, while controls were individuals with negative molecular test results during the same period. Individuals reporting a positive test for SARS-CoV-2 infection prior to the study period were not eligible to participate. This analysis excludes data from children aged 0-17 years, who were generally ineligible for COVID-19 vaccination over the study period.

Each day during the study period, we randomly selected from among all individuals with a telephone number and a positive or negative SARS-CoV-2 test result within nine regions of the state, with intent to enroll equally across each region (regions and the counties comprising them are listed in Table S4 ). For each case who consented and completed the study interview, we attempted to enroll and interview one control matched on age group (18-39, 40-64, ≥65 years), sex, region, and week of SARS-CoV-2 test.

We designed and implemented a standardized questionnaire to be delivered via facilitated telephone interviews in English or Spanish including data on participant demographics, symptoms, and vaccination status. We asked participants to indicate whether they had received any COVID-19 vaccine, and to reference their COVID-19 vaccination card to report the manufacturer, number, and dates of doses received. We also asked unvaccinated participants whether they would be willing to receive a COVID-19 vaccine, when it was available to them; if participants indicated they were not likely to receive a vaccine or unsure about receiving a vaccine, we asked for their reasons for vaccine hesitancy.

The study protocol was granted a non-research determination by the State of California Health and Human Services Agency Committee for the Protection of Human Subjects (project number: 2021-034).

We measured VE as one minus the matched odds ratio of prior vaccination among cases relative to controls within strata defined by age group, sex, region, and testing week. We defined the vaccine exposure as receipt of BNT162b2 or mRNA-1273, within differing numbers of days since receipt of the first or second dose. We estimated effects using conditional logistic regression models (R version 3.6.1; R Foundation for Statistical Computing; Vienna, Austria).

We also conducted Chi-Square tests for differences in the: proportion of individuals testing positive for SARS-CoV-2 infection among those who received BNT162b2 or mRNA-1273; proportion of cases reporting any symptoms in the two weeks before their testing date among vaccine recipients and non-recipients; and proportion of unvaccinated individuals reporting hesitancy to receive vaccination across differing demographic groups. We conducted hypothesis testing with two-sided p<0.05.

Our study recruited 325 cases and 320 controls. Among cases, 23 (7%) and 13 (4%) reported receiving at least one dose of BNT162b2 or mRNA-1273, respectively. Eight cases (2%) were considered to be fully vaccinated at the time of testing based on self-reported vaccination status (Figure 1 ; Table S1 ). Among fully vaccinated individuals, VE was 86% (67-94%) (Figure 1 ). Case status was not significantly associated with vaccine product received (! !"#$ % = 0.149; ) = 0.7). Presence of symptoms did not differ significantly among vaccinated and unvaccinated cases (! !"#$ % = 1.315; ) = 0.3); 26% of cases did not report symptoms. Thirteen (4%, 13/325) cases were hospitalized; of these, eleven were unvaccinated, and two were incompletely vaccinated.

Within the second week after receipt of a first dose, VE was 66% (-69-93%). Within the second week after receipt of a second dose, VE was 78% (23-94%).

Overall, 133 (32%) of 415 unvaccinated participants (including 78/242 [32%] unvaccinated cases and 55/173 [32%] unvaccinated controls) indicated they were unlikely or unsure about receiving a COVID-19 vaccine when eligible ( Table 2 ; Table S2 ). Residents of rural regions (! !"#$ % = 24.0; ) = 0.002) were over-represented among those reporting vaccine hesitancy, whereas differences in vaccine hesitancy by age, sex, household income, and race/ethnicity were not evident (Table S3) . Fears over vaccine safety (30/127 [24%]) or side effects (33/127 [26%]) were the most common concerns.

We find that authorized mRNA-based COVID-19 vaccines confer robust protection against COVID-19 under real-world conditions in the general population. Moreover, we identify partial protection before two weeks after receipt of the second dose, in agreement with previous estimates. 8 While our point estimate of 86% VE is lower than efficacy findings in earlier randomized trials 1,2 and marginally below that of a recent observational study, 7 several considerations should inform comparison of findings. Primary trial endpoints were COVID-19 diagnoses involving new-onset acute symptoms and SARS-CoV-2 detection, whereas 26% of cases in our study reported no symptoms. The majority of sequenced SARS-CoV-2 isolates in California over the study period represented B.1.427/B.1.429 variants associated with immune escape, which may reduce VE. 9,10 Importantly, though, our results indicate substantial protection despite widespread circulation of these variants.

We identified rural-urban divides in vaccine enthusiasm. Whereas concerns over vaccine safety and side effects were the most common reasons for hesitancy, these concerns were reported by only a minority of all participants who expressed hesitancy about receiving COVID-19 vaccination, when eligible. Differing messaging and outreach strategies will thus be needed to address barriers to vaccine acceptance across communities.

While observational studies face risks of bias, similarity of our estimates to those of other studies and stepwise increases in VE with time since receipt of each dose support external validity. 7, 8, 11 While the current sample size offered limited statistical power for first-dose VE estimation, enrollment in this study is ongoing. Analyses including larger samples will enable comparison of estimates across products and population subgroups. Meanwhile, our findings indicate that vaccine rollout is preventing COVID-19 in the general population of California. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 10, 2021. ; All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 10, 2021. ; https://doi.org/10.1101/2021.04.08.21255135 doi: medRxiv preprint Figure S1 : Sensitivity analyses excluding individuals (N=39) without access to vaccination cards. Lines denote 95% confidence intervals, respectively, for estimates of vaccine effectiveness. Estimates were calculated via conditional logistic regression. All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 10, 2021. ; https://doi.org/10.1101/2021.04.08.21255135 doi: medRxiv preprint

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