Abstract
Purpose
Heart transplant (HT) recipients are at high risk for poor immunity after COVID-19 vaccination. A multidose vaccine strategy is thus recommended, but the clinical outcomes and immune correlates of clinical protection against SARS-CoV-2 are unknown.
Methods
In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine between March 2020 and May 2022, patients were prospectively assessed for vaccine-induced neutralizing antibodies (nAbs) against the wild-type virus and Delta and Omicron variants (using live virus micro-neutralization assays), and for T-cell response. Clinical outcomes included COVID-19 infection and kidney function. Comparative analyses with controls were conducted to identify correlates of infection.
Results
We characterized 67 (43.8%) COVID-19 infections. Repeat vaccination decreased the risk of contracting COVID-19 (HR 0.05, p=0.02; HR 0.02, p=0.01; HR 0.01, p=0.004; for 1-2-, 3- and 4- doses, respectively) and of severe-critical disease (HR 0.003, p<0.001). Vaccine prevention of infectivity was lower for the Omicron. Vaccine-induced nAbs against the Delta and Omicron variants were associated with a reduced risk for COVID-19 (HR 0.36, p=0.01; HR 0.21, p=0.01, respectively), whereas a vaccine-induced T-cell response was not (p=0.6). The optimal nAbs titer thresholds for the prediction of COVID-19 were 48 (wild-type), 24 (Delta), and 4 (Omicron). COVID-19 was associated with an increased risk of long-term renal dysfunction (OR 17.4, p<0.001), with the extent of deterioration correlating with the severity of acute COVID-19.
Conclusion
A repeat vaccination strategy provides protection from severe infection with SARS-CoV-2 and to a lesser extent from mild infection. BNT162b2-vaccine-induced nAbs conferred clinical immunity. Our findings could assist in rationally focusing improvements for future vaccines and immunotherapeutic for SARS-CoV-2 and population-tailored vaccination strategy.
