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ImportanceRecent sublineages of the SARS-CoV-2 Omicron variant, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 following vaccination. ObjectiveTo evaluate the association between COVID-19 mRNA vaccination with 2, 3, or 4 doses among immunocompetent adults and the risk of medically attended COVID-19 illness during a period of BA.4/BA.5 predominant circulation; to evaluate the relative severity of COVID-19 in hospitalized cases across Omicron BA.1, BA.2/BA.2.12.1, and BA.4/BA.5 sublineage periods. Setting, Design and ParticipantsTest-negative study of adults with COVID-19-like illness (CLI) and molecular testing for SARS-CoV-2 conducted in 10 states from December 16, 2021, to August 20, 2022. ExposuremRNA COVID-19 vaccination. Main Outcomes and MeasuresEmergency department/urgent care encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. The adjusted odds ratio (OR) for the association between prior vaccination and medically attended COVID-19 was used to estimate VE, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as reference group). Among hospitalized case-patients, demographic and clinical characteristics and in-hospital outcomes including ICU admission and death were compared across sublineage periods. ResultsBetween June 19 - August 20, 2022, 82,229 ED/UC and 21,007 hospital encounters were included for the BA.4/BA.5 vaccine effectiveness analysis. Among adults hospitalized with CLI, the adjusted odds ratio (OR) was 0.75 (95% CI: 0.68-0.83) for receipt of 2 vaccine doses at [≥]150 days after receipt, 0.32 (95% CI: 0.20-0.50) for a third dose 7-119 days after receipt, and 0.64 (95% CI: 0.58-0.71) for a third dose [≥]120 days (median 235 days) after receipt for cases vs controls. For COVID-19-associated hospitalization, among patients ages [≥]65 years 7-59 and [≥]60 days (median 88 days) after a fourth dose, ORs were 0.34 (95% CI: 0.25-0.47) and 0.43 (95% CI: 0.34-0.56), respectively. Among hospitalized cases, ICU admission and/or in-hospital death occurred in 21.4% during the BA.1 vs 14.7% during the BA.4/BA.5 period (standardized mean difference: 0.17). ConclusionVE against medically attended COVID-19 illness decreased over time since last dose; receipt of one or two booster doses increased effectiveness over a primary series alone. KEY POINTS QuestionWhat is the association between receipt of first-generation COVID-19 mRNA vaccines and medically attended COVID-19 during Omicron BA.4/BA.5 sublineage predominance? FindingsThis test-negative analysis included 82,229 emergency department or urgent care encounters and 21,007 hospitalizations for COVID-19-like illness. Among hospitalized patients, the likelihood of recent vaccination (7-119 days) with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower (odds ratio, 0.32) in cases than SARS-CoV-2-negative controls, but with lower associated protection [≥]120 days post-vaccination (odds ratio, 0.64). MeaningFirst-generation COVID-19 vaccines were associated with protection against COVID-19 during the Omicron BA.4/BA.5 sublineage-predominant periods but this declined over time.
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BACKGROUNDInformation is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions. METHODSProspective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020--April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). VE was calculated as 100%x(1-hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation. RESULTSSARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially ([≥]14 days post-dose-1 to 13 days after dose-2) or fully ([≥]14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%-97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants. CONCLUSIONSAuthorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.
