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Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization. Design: Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE). Setting: Twenty-one hospitals in the United States (US). Participants: 3,181 adults hospitalized with an acute respiratory illness between December 26, 2021 and April 30, 2022, a period of SARS-CoV-2 Omicron variant (BA.1, BA.2) predominance. Participants included 1,572 (49%) case-patients with laboratory confirmed COVID-19 and 1,609 (51%) control patients who tested negative for SARS-CoV-2. Median age was 64 years, 48% were female, and 21% were immunocompromised; 798 (25%) were vaccinated with a primary series plus booster, 1,326 (42%) were vaccinated with a primary series alone, and 1,057 (33%) were unvaccinated. Main Outcome Measures: VE against COVID-19 hospitalization was calculated for a primary series plus a booster and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. VE analyses were stratified by immune status (immunocompetent; immunocompromised) because the recommended vaccine schedules are different for these groups. The primary analysis evaluated all COVID-19 vaccine types combined and secondary analyses evaluated specific vaccine products. Results: Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71-82%), and for a primary series alone was 44% (95% CI: 31-54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients. Conclusions: Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant.
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ObjectivesTo characterize the clinical severity of COVID-19 caused by Omicron, Delta, and Alpha SARS-CoV-2 variants among hospitalized adults and to compare the effectiveness of mRNA COVID-19 vaccines to prevent hospitalizations caused by each variant. DesignA case-control study of 11,690 hospitalized adults. SettingTwenty-one hospitals across the United States. ParticipantsThis study included 5728 cases hospitalized with COVID-19 and 5962 controls hospitalized without COVID-19. Cases were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: Alpha (March 11 to July 3, 2021), Delta (July 4 to December 25, 2021), and Omicron (December 26, 2021 to January 14, 2022). Main Outcome MeasuresVaccine effectiveness was calculated using a test-negative design for COVID-19 mRNA vaccines to prevent COVID-19 hospitalizations by each variant (Alpha, Delta, Omicron). Among hospitalized patients with COVID-19, disease severity on the WHO Clinical Progression Ordinal Scale was compared among variants using proportional odds regression. ResultsVaccine effectiveness of the mRNA vaccines to prevent COVID-19-associated hospitalizations included: 85% (95% CI: 82 to 88%) for 2 vaccine doses against Alpha; 85% (95% CI: 83 to 87%) for 2 doses against Delta; 94% (95% CI: 92 to 95%) for 3 doses against Delta; 65% (95% CI: 51 to 75%) for 2 doses against Omicron; and 86% (95% CI: 77 to 91%) for 3 doses against Omicron. Among hospitalized unvaccinated COVID-19 patients, severity on the WHO Clinical Progression Scale was higher for Delta than Alpha (adjusted proportional odds ratio [aPOR] 1.28, 95% CI: 1.11 to 1.46), and lower for Omicron than Delta (aPOR 0.61, 95% CI: 0.49 to 0.77). Compared to unvaccinated cases, severity was lower for vaccinated cases for each variant, including Alpha (aPOR 0.33, 95% CI: 0.23 to 0.49), Delta (aPOR 0.44, 95% CI: 0.37 to 0.51), and Omicron (aPOR 0.61, 95% CI: 0.44 to 0.85). ConclusionsmRNA vaccines were highly effective in preventing COVID-19-associated hospitalizations from Alpha, Delta, and Omicron variants, but three vaccine doses were required to achieve protection against Omicron similar to the protection that two doses provided against Delta and Alpha. Among adults hospitalized with COVID-19, Omicron caused less severe disease than Delta, but still resulted in substantial morbidity and mortality. Vaccinated patients hospitalized with COVID-19 had significantly lower disease severity than unvaccinated patients for all the variants.
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The novel coronavirus pandemic incited unprecedented demand for assays that detect viral nucleic acids, viral proteins, and corresponding antibodies. The 320 molecular diagnostics in receipt of FDA emergency use authorization mainly focus on viral detection; however, no currently approved test can be used to infer infectiousness, i.e., the presence of replicable virus. As the number of tests conducted increased, persistent SARS-CoV-2 RNA positivity by RT-PCR in some individuals led to concerns over quarantine guidelines. To this end, we attempted to design an assay that reduces the frequency of positive test results from individuals who do not shed culturable virus. We describe multiplex quantitative RT-PCR (qRT-PCR) assays that detect genomic RNA (gRNA) and subgenomic RNA (sgRNA) species of SARS-CoV-2, including spike (S), nucleocapsid (N), membrane (M), envelope (E), and ORF8. The absolute copy number of each RNA target was determined in longitudinal specimens from a household transmission study. Calculated viral RNA levels over the 14-day follow up period were compared with antigen testing and self-reported symptoms to characterize the clinical and molecular dynamics of infection and infer predictive values of these qRT-PCR assays relative to culture isolation. When detection of sgS RNA was added to the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel, we found a qRT-PCR positive result was 98% predictive of a positive culture (negative predictive value was 94%). Our findings suggest sgRNA presence correlates with active infection, may help identify individuals shedding culturable virus, and that similar multiplex assays can be adapted to current and future variants.
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BackgroundAs SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. MethodsIn a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. ResultsAmong 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses [≥]14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were [≥]50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). ConclusionDuring March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.