Effectiveness of a fourth dose of mRNA-1273 against COVID-19 among older adults in the United States: Interim results from an observational cohort study.

We evaluated relative vaccine effectiveness (rVE) of 4- vs. 3-dose mRNA-1273 against SARS-CoV-2 infection, and COVID-19 hospitalization and death in immunocompetent adults aged ≥50 years at Kaiser Permanente Southern California. We included 178,492 individuals who received a fourth dose of mRNA-1273, and 178,492 randomly selected 3-dose recipients who were matched to 4-dose recipients by age, sex, race/ethnicity, and third dose date. Adjusted 4- vs. 3-dose rVE against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospitalization death were 25.9 % (23.5 %, 28.2 %), 67.3 % (58.7 %, 74.1 %), and 72.5 % (-35.9 %, 95.2 %), respectively. Adjusted rVE against SARS-CoV-2 infection ranged between 19.8 % and 39.1 % across subgroups. Adjusted rVE against SARS-CoV-2 infection and COVID-19 hospitalization decreased 2-4 months after the fourth dose. Four mRNA-1273 doses provided significant protection against COVID-19 outcomes compared with 3 doses, consistent in various subgroups of demographic and clinical characteristics, although rVE varied and waned over time.

Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: A prospective observational cohort study.

BACKGROUND: Data on the effectiveness of the 3-dose mRNA-1273 primary series are limited, particularly in comparison to 2 doses. Given suboptimal COVID-19 vaccine uptake among immunocompromised populations, it is important to monitor the effectiveness of fewer than the recommended doses in this population. METHODS: We conducted a matched cohort study at Kaiser Permanente Southern California to evaluate the relative vaccine effectiveness (rVE) of the 3-dose series vs 2 doses of mRNA-1273 in preventing SARS-CoV-2 infection and severe COVID-19 outcomes among immunocompromised individuals. RESULTS: We included 21,942 3-dose recipients who were 1:1 matched with randomly selected 2-dose recipients (third doses accrued 08/12/2021-12/31/2021, with follow-up through 01/31/2022). Adjusted rVE of 3 vs 2 doses of mRNA-1273 against SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 hospital death were 55.0 % (95 % CI: 50.8-58.9 %), 83.0 % (75.4-88.3 %), and 87.1 % (30.6-97.6 %), respectively. CONCLUSION: Three doses of mRNA-1273 were associated with a significantly higher rVE against SARS-CoV-2 infection and severe outcomes, compared to 2 doses. These findings were consistent across subgroups of demographic and clinical characteristics, and mostly consistent across subgroups of immunocompromising conditions. Our study highlights the importance of completing the 3-dose series for immunocompromised populations.

Effectiveness of mRNA-1273 vaccine booster against COVID-19 in immunocompetent adults.

BACKGROUND: A prospective cohort study at Kaiser Permanente Southern California was conducted to evaluate the relative vaccine effectiveness (rVE) of a booster-dose vs. 2-dose primary series of mRNA-1273 in immunocompetent individuals during periods of Delta and Omicron predominance. METHODS: Immunocompetent adults who received a booster dose of mRNA-1273 from October through December 2021 were matched 1:1 to randomly selected 2-dose mRNA-1273 recipients by age, sex, race/ethnicity, and second dose date, and followed up through January 2022. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs), comparing outcomes (SARS-CoV-2 infection, and COVID-19 hospitalization and hospital death) in the booster-dose and 2-dose groups. Adjusted rVE (%) was calculated as (1-aHR)x100. aHRs and rVEs were also estimated for SARS-CoV-2 infection by subgroups (age, sex, race/ethnicity, history of SARS-CoV-2 infection, pregnancy, chronic diseases), and for SARS-CoV-2 infection and severe COVID-19 disease by month of follow-up. RESULTS: The study included 431,328 booster-dose vaccinated adults matched to 431,328 2-dose vaccinated adults. rVE was 61.3% (95%CI: 60.5-62.2%) against SARS-CoV-2 infection, 89.0% (86.2-91.2%) against COVID-19 hospitalization, and 96.0% (68.0-99.5%) against COVID-19 hospital death. rVE against SARS-CoV-2 infection ranged from 55.6% to 66.7% across all subgroups. rVE against SARS-CoV-2 infection decreased from 67.1% (0-<1 month of follow-up) to 30.5% (2-<3 months). For COVID-19 hospitalization, rVE decreased from 91.2% (0-<1 month) to 78.7% (2-<3 months). CONCLUSIONS: Among immunocompetent adults, the mRNA-1273 booster conferred additional protection against SARS-CoV-2 infection and severe COVID-19 disease compared to the 2-dose mRNA-1273 primary series during periods of Delta and Omicron predominance.

Effectiveness of mRNA-1273 vaccination against 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. This test-negative case-control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 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 is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is 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 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.