Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case-control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged [≥]18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection was high and waned slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate to high (61.0%-90.6% 14-30 days post third dose) and waned rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged between 64.3%-75.7%, and was low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 was 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 was 88.5%. Evaluation of the updated bivalent booster is warranted.

Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022

BackgroundWe estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. MethodsBetween October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. ResultsAmong 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. ConclusionsIn this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose.

Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants

SARS-CoV-2 omicron (B.1.1.529) variant is highly transmissible with potential immune escape. We conducted a test-negative case-control study to evaluate mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron or delta. The large, diverse study population included 26,683 SARS-CoV-2 test-positive cases with variant determined by spike gene status (16% delta, 84% omicron). The 2-dose VE against omicron infection at 14-90 days was 44.0% (95% CI, 35.1-51.6%) but declined quickly. The 3-dose VE was 93.7% (92.2-94.9%) and 86.0% (78.1-91.1%) against delta infection and 71.6% (69.7-73.4%) and 47.4% (40.5-53.5%) against omicron infection at 14-60 days and >60 days, respectively. The 3-dose VE was 29.4% (0.3-50.0%) against omicron infection in immunocompromised individuals. The 3-dose VE against hospitalization with delta or omicron was >99%. Our findings demonstrate high, durable 3-dose VE against delta infection but lower effectiveness against omicron infection, particularly among immunocompromised people. However, 3-dose VE was high against hospitalization with delta or omicron.

Durability of mRNA-1273 against COVID-19 in the time of Delta: Interim results from an observational cohort study

BackgroundWe conducted a prospective cohort study at Kaiser Permanente Southern California to study the vaccine effectiveness (VE) of mRNA-1273 over time and during the emergence of the Delta variant. MethodsThe cohort for this planned interim analysis consisted of individuals aged [≥]18 years receiving 2 doses of mRNA-1273 through June 2021, matched 1:1 to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through September 2021. Outcomes were SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) comparing outcomes in the vaccinated and unvaccinated groups. Adjusted VE (%) was calculated as (1-aHR)x100. HRs and VEs were also estimated for SARS-CoV-2 infection by age, sex, race/ethnicity, and during the Delta period (June-September 2021). VE against SARS-CoV-2 infection and COVID-19 hospitalization was estimated at 0-<2, 2-<4, 4-<6, and 6-<8 months post-vaccination. Results927,004 recipients of 2 doses of mRNA-1273 were matched to 927,004 unvaccinated individuals. VE (95% CI) was 82.8% (82.2-83.3%) against SARS-CoV-2 infection, 96.1% (95.5-96.6%) against COVID-19 hospitalization, and 97.2% (94.8-98.4%) against COVID-19 hospital death. VE against SARS-CoV-2 infection was similar by age, sex, and race/ethnicity, and was 86.5% (84.8-88.0%) during the Delta period. VE against SARS-CoV-2 infection decreased from 88.0% at 0-<2 months to 75.5% at 6-<8 months. ConclusionsThese interim results provide continued evidence for protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period, and against COVID-19 hospitalization and hospital death. SummaryThis prospective cohort study provides evidence for continued protection of 2 doses of mRNA-1273 against SARS-CoV-2 infection over 8 months post-vaccination and during the Delta period. VE against COVID-19 hospitalization remained robust and stable over the same period.

Recombinant adjuvanted zoster vaccine and reduced risk of COVID-19 diagnosis and hospitalization in older adults

BackgroundVaccines may elicit long-term boosting of innate immune responses that can help protect against COVID-19. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and COVID-19 outcomes at Kaiser Permanente Southern California. MethodsIn a cohort design, adults aged [≥]50 years who received [≥]1 RZV dose prior to 3/1/2020 were matched 1:2 to unvaccinated individuals and followed until 12/31/2020. Adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive SARS-CoV-2 test and controls had only negative tests, from 3/1/2020-12/31/2020. Adjusted odds ratios (aOR) and 95% CIs for prior receipt of RZV were estimated using logistic regression. ResultsIn the cohort design, 149,244 RZV recipients were matched to 298,488 unvaccinated individuals. The aHRs (95% CI) for COVID-19 diagnosis and hospitalization were 0.84 (0.81-0.87) and 0.68 (0.64-0.74), respectively. In the test-negative design, 8.4% of 75,726 test-positive cases and 13.1% of 340,898 test-negative controls had received [≥]1 RZV dose. The aOR (95% CI) was 0.84 (0.81-0.86). ConclusionRZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization, suggesting RZV elicits heterologous protection, possibly through trained immunity.

Effectiveness of mRNA-1273 against Delta, Mu, and other emerging variants

BackgroundReal-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE. MethodsWe conducted a test-negative case-control study at Kaiser Permanente Southern California. Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021. Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date. Outcomes included SARS-CoV-2 infection and hospitalization. Exposures were 2 doses or 1 dose of mRNA-1273 [≥]14 days prior to specimen collection versus no COVID-19 vaccination. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, adjusting for confounders. VE was calculated as (1-odds ratio)x100%. ResultsThe study included 8,153 cases and their matched controls. Two-dose VE (95% confidence interval) was 86.7% (84.3-88.7%) against Delta infection, 98.4% (96.9-99.1%) against Alpha, 90.4% (73.9-96.5%) against Mu, 96-98% against other identified variants, and 79.9% (76.9-82.5%) against unidentified variants. VE against Delta declined from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged [≥]65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. ConclusionsTwo doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants. However, VE against Delta moderately declined with increasing time since vaccination. Trial Registration NumberNot applicable FundingModerna Inc.