Background Population-based data from the United States on the effectiveness of the three coronavirus disease 2019 (Covid-19) vaccines currently authorized by the Food and Drug Administration are limited. Whether declines in effectiveness are due to waning immunity, the B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or other causes is unknown. Methods We used data for 8,690,825 adults in New York State to assess the effectiveness of the BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines against laboratory-confirmed Covid-19 and hospitalization with Covid-19 (i.e., Covid-19 diagnosed at or after admission). We compared cohorts defined according to vaccine product received, age, and month of full vaccination with age-specific unvaccinated cohorts by linking statewide testing, hospital, and vaccine registry databases. We assessed vaccine effectiveness against Covid-19 from May 1 through September 3, 2021, and against hospitalization with Covid-19 from May 1 through August 31, 2021. Results There were 150,865 cases of Covid-19 and 14,477 hospitalizations with Covid-19. During the week of May 1, 2021, when the delta variant made up 1.8% of the circulating variants, the median vaccine effectiveness against Covid-19 was 91.3% (range, 84.1 to 97.0) for BNT162b2, 96.9% (range, 93.7 to 98.0) for mRNA-1273, and 86.6% (range, 77.8 to 89.7) for Ad26.COV2.S. Subsequently, effectiveness declined contemporaneously in all cohorts, from a median of 93.4% (range, 77.8 to 98.0) during the week of May 1 to a nadir of 73.5% (range, 13.8 to 90.0) around July 10, when the prevalence of the delta variant was 85.3%. By the week of August 28, when the prevalence of the delta variant was 99.6%, the effectiveness was 74.2% (range, 63.4 to 86.8). Effectiveness against hospitalization with Covid-19 among adults 18 to 64 years of age remained almost exclusively greater than 86%, with no apparent time trend. Effectiveness declined from May through August among persons 65 years of age or older who had received BNT162b2 (from 94.8 to 88.6%) or mRNA-1273 (from 97.1 to 93.7%). The effectiveness of Ad26.COV2.S was lower than that of the other vaccines, with no trend observed over time (range, 80.0 to 90.6%). Conclusions The effectiveness of the three vaccines against Covid-19 declined after the delta variant became predominant. The effectiveness against hospitalization remained high, with modest declines limited to BNT162b2 and mRNA-1273 recipients 65 years of age or older.

† A COVID-19 case in a fully vaccinated person occurred when SARS-CoV-2 RNA or antigen was detected in a respiratory specimen collected ≥14 days after completing the primary series of a COVID-19 vaccine with Food and Drug Administration (FDA) approval or emergency use authorization. The COVID-19 case definition, including criteria to distinguish a new case from an existing case, is per the July 2021 update to the national standardized surveillance case definition and national notification for 2019 novel coronavirus disease (COVID-19) (21-ID-01) (https://ndc.services.cdc.gov/case-definitions/ coronavirus-disease-2019-2021/). Fully vaccinated persons were those with a completed primary series of 2 doses of the Pfizer-BioNTech or Moderna mRNA vaccine or a single dose of the Janssen vaccine (https://www.cdc.gov/ coronavirus/2019-ncov/vaccines/stay-up-to-date.html). A COVID-19 case in an unvaccinated person occurred when the person did not receive any FDAauthorized COVID-19 vaccine doses before the specimen collection date. Cases were excluded in partially vaccinated persons who received at least one FDAauthorized or approved vaccine dose but did not complete a primary series ≥14 days before collection of a respiratory specimen with SARS-CoV-2 RNA or antigen detected. Ascertaining vaccination status for COVID-19 patients through active linkage of case surveillance and immunization information systems typically assumes that cases among persons who are unmatched to the registry are unvaccinated. This analysis represents the combined impact of the Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccines, which had different clinical efficacies against confirmed infection. Information on different FDA-authorized and approved COVID-19 vaccine products, including clinical efficacy, is available online. https://www.cdc.gov/coronavirus/2019-ncov/ vaccines/different-vaccines.html

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Vaccinated, no previous COVID-19 diagnosis Unvaccinated, previous COVID-19 diagnosis Vaccinated, previous COVID-19 diagnosis Unvaccinated, previous COVID-19 diagnosis Vaccinated, previous COVID-19 diagnosis Cases, California May 30-Jun 5 20.