Hybrid immunity provides stronger protection against SARS-CoV-2 infection than vaccination alone: Evidence from a population-based active monitoring study.

BACKGROUND

Hybrid immunity, defined as vaccination plus prior infection, induces higher antibody levels than vaccination alone, but there is limited evidence on whether this enhanced immunological response translates into greater real-world protection against SARS-CoV-2 infection, particularly in population-based active-monitoring cohorts.

METHODS

We used data from RESPIRA, a population-based longitudinal cohort in Costa Rica that enrolled participants between November 2020 and October 2021 and followed them monthly for two years with guided saliva self-collection. We compared PCR testing results from saliva specimens collected from individuals with hybrid immunity (PCR-confirmed infection before enrollment plus two vaccine doses; N = 1157 specimens) to those from participants with two vaccine doses and no evidence of prior infection (N = 1712 specimens). All selected samples were collected between June 2021 and May 2022. The two groups were compared using GEE models adjusted for demographic, specimen-related and epidemiologic factors.

RESULTS

Hybrid immunity was associated with substantially lower risk of SARS-CoV-2 infection measured by PCR in saliva samples compared with vaccination alone (adjusted OR = 0.61 [0.43-0.84]). Findings were consistent when using self-reported COVID-19 diagnosis as the outcome.

CONCLUSIONS

Hybrid immunity conferred stronger protection against SARS-CoV-2 infection than two vaccine doses alone.