Optimizing COVID-19 vaccination for older adults: superior efficacy of heterologous regimens in reducing infection and mortality rates among patients aged 80 years and older during the Omicron BA.5/BF.7 outbreak

BACKGROUND: Following the adjustment of COVID-19 control policies in mainland China, particularly during the Omicron BA.5 and BF.7 waves, evaluating vaccine effectiveness in individuals aged ≥ 80 years is of critical importance. PATIENTS AND METHODS: This retrospective study included 2,325 hospitalized patients aged 80 years and older from four hospitals between December 9, 2022, and January 27, 2023. We assessed the associations of vaccination dose, vaccination regimen, and the interval since the last vaccination with SARS-CoV-2 infection and mortality. Univariable and multivariable logistic regression analyses were performed to adjust for baseline imbalances across vaccination groups. An exploratory NAb analysis was conducted in 138 patients with paired serum samples at admission and discharge to evaluate immune responses associated with different vaccination strategies. RESULTS: In the unadjusted analyses, SARS-CoV-2 infection and mortality rates decreased with increasing vaccine doses. After adjustment for age, diabetes, and hyperlipidemia, receipt of 1, 2, and 3 vaccine doses was associated with lower odds of SARS-CoV-2 infection compared with no vaccination, with adjusted ORs of 0.644 (95% CI: 0.445-0.931, P = 0.019), 0.579 (95% CI: 0.407-0.823, P = 0.002), and 0.448 (95% CI: 0.332-0.607, P < 0.001), respectively. Three-dose vaccination was also associated with lower odds of mortality (OR = 0.563, 95% CI: 0.380-0.835, P = 0.004). In the regimen-based model, CoronaVac plus ZF2001 was associated with lower odds of infection (OR = 0.456, 95% CI: 0.235-0.885, P = 0.020) and mortality (OR = 0.410, 95% CI: 0.123-0.878, P = 0.047) after adjustment. In the exploratory NAb subgroup analysis, patients receiving CoronaVac plus ZF2001 showed higher NAb levels at both admission and discharge. CONCLUSIONS: During the Omicron BA.5/BF.7 wave, receipt of three COVID-19 vaccine doses was associated with lower risks of SARS-CoV-2 infection and mortality among hospitalized patients aged 80 years and older. The heterologous regimen of CoronaVac plus ZF2001 was associated with lower risks of infection and mortality and higher NAb levels. These findings support the potential value of optimized booster and heterologous vaccination strategies for improving COVID-19-related outcomes in this high-risk older population. CLINICAL TRIAL: N/A.