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Neutralizing antibody plays a key role in protective immunity against COVID-19. As increasingly distinct variants circulate, debate continues regarding the value of adding novel variants to SARS-CoV-2 vaccines. In this study, we have analyzed live virus neutralization titers against WA1, Delta, BA.1, BA.2, and BA.5 in 187 hospitalized patients infected with Delta or Omicron strains. This information will be useful in selection of the SARS-CoV-2 strains to include in an updated vaccine. Our results show that unvaccinated Delta infected patients made a highly biased neutralizing antibody response towards the infecting Delta strain with slightly lower responses against the WA1 strain, but with strikingly lower titers against BA.1, BA.2, and BA.5. Delta infected patients that had been previously vaccinated with the WA1 containing COVID vaccine made equivalent responses to WA1 and Delta strains, but still had very low neutralizing antibody responses to Omicron strains. In striking contrast, both unvaccinated and vaccinated Omicron patients exhibited a more balanced ratio of Omicron virus neutralization compared to neutralization of ancestral strains. Interestingly, Omicron patients infected with BA.1 or BA.2 had detectable neutralizing antibody titers to BA.5, but these titers were lower than neutralization titers to BA.1 and BA.2. Taken together, these results suggest that inclusion of the Omicron BA.5 strain in a SARS-CoV-2 vaccine would be beneficial in protection against the widely circulating BA.5 variant. DisclaimerThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
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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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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.
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PurposeTo describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). Materials and MethodsA retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. ResultsOur cohort had median age of 61 (IQR 45-74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74-19.48), former (OR 8.06, CI 1.51-43.06) and current smoking status (OR 10.33, CI 1.43-74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11-0.96), procalcitonin (OR 1.27, CI 1.02-1.57), IL-6 (OR 1.17, CI 1.03-1.33), ferritin (OR 1.05, CI 1.005-1.11), LDH (OR 1.57, 95% CI 1.13-2.17) and CRP (OR 1.13, CI 1.06-1.21), were associated with IMV by univariate analysis. ConclusionsObesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.