Publication date: May 23, 2025

The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact. Therapeutic strategies to bridge the crucial ‘lockdown’ timespan between the emergence of a new virus and vaccine rollout are needed. We recently demonstrated that intranasal (i. n.) administration of COVID-19 convalescent plasma (CCP) in sentinel hamsters can limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from acutely infected index littermates. The current study investigates if functional immunity develops during i. n. prophylaxis in the same model. Lung tissue was free from infectious virus and pneumonia in sentinel hamsters after i. n. CCP prophylaxis, unlike those receiving non-immune control plasma (NIP). However, throat swabs from both groups contained viral RNA similar to intentionally infected index littermates. Anti-receptor binding domain (RBD) antibodies were detected in plasma from both sentinel groups two days after it showed in index littermates. This immune response was functional because all sentinel hamsters were protected from reinfection by the same viral strain. Our findings demonstrate that i. n. CCP prophylaxis prevents lung disease in hamsters by restraining the infection to the upper respiratory tract, while still promoting a functional humoral immune response that protects against reinfection.

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