Intranasal administration of convalescent plasma protects against SARS-CoV-2 infection in hamsters

Summary Background Convalescent plasma (CP) transfusion is an early option for treating infections with pandemic potential, often preceding vaccine or antiviral drug rollout. Heterogenous findings from randomized clinical trials on transfusion of COVID-19 CP (CCP) have been reported. However, meta-analysis suggests that transfusion of high titer CCP is associated with a mortality benefit for COVID-19 outpatients or inpatients treated within 5 days after symptom onset, indicating the importance of early administration. Methods We tested if CCP is an effective prophylactic against SARS-CoV-2 infection by the intranasal administration of 25 μL CCP/nostril (i.e. 0.01–0.06 mg anti-RBD antibodies/kg) in hamsters exposed to infected littermates. Findings In this model, 40% of CCP treated hamsters were fully protected and 40% had significantly reduced viral loads, the remaining 20% was not protected. The effect seems dose-dependent because high-titer CCP from a vaccinated donor was more effective than low-titer CCP from a donation prior to vaccine rollout. Intranasal administration of human CCP resulted in a reactive (immune) response in hamster lungs, however this was not observed upon administration of hamster CCP. Interpretation We conclude that CCP is an effective prophylactic when used directly at the site of primary infection. This option should be considered in future prepandemic preparedness plans. Funding 10.13039/100012331 Flanders Innovation & Entrepreneurship (VLAIO) and the Foundation for Scientific Research of the Belgian Red Cross Flanders .