Efficacy of combined COVID-19 convalescent plasma with oral RNA-dependent RNA polymerase inhibitor treatment versus neutralizing monoclonal antibody therapy in COVID-19 outpatients: a multi-center, non-inferiority, open-label randomized controlled trial (PlasMab)

Abstract

ABSTRACT The effectiveness of neutralizing monoclonal antibodies against emerging variants with spike protein mutations has been limited. Early high-titer convalescent plasma therapy (CPT) tends to be effective and a potential treatment option for COVID-19 outpatient treatment. An open-label, 1:1, randomized controlled trial compared the efficacy of high neutralizing titer CPT with favipiravir (CPT-FPV) versus sotrovimab. The study aimed to evaluate the non-inferiority of CPT-FPV treatment compared to sotrovimab in preventing hospitalization within 14 and 28 days. Among the 136 randomized participants, 68 received CPT-FPV, while 68 received sotrovimab. The study demonstrated that CPT-FPV was non-inferior to sotrovimab in preventing hospitalization within 14 and 28 days. No significant differences between the two treatment arms were observed in emergency room visits, oxygen supplementation, or mortality. Although there were no significant disparities in radiological, virological, or inflammatory marker outcomes, sotrovimab exhibited a more pronounced reduction in IL-6 levels during days 2–5 and lower MCP-1 levels on day 14. High neutralizing titer convalescent plasma and favipiravir demonstrated non-inferior to sotrovimab in preventing hospitalization, emergency room visit, oxygen supplementation, and mortality in mild-to-moderate COVID-19. The evidence may be a choice for treatment for new variants despite the need for further study. (The trial protocol was registered in the Thai clinical trials registry no. 20220319002.) IMPORTANCE This pivotal study reveals that high neutralizing titer COVID-19 convalescent plasma therapy (CPT) combined with favipiravir (FPV) is non-inferior to sotrovimab in preventing hospitalization and severe outcomes in outpatients with mild-to-moderate COVID-19 and high-risk comorbidities. It underscores the potential of CPT-FPV as a viable alternative to neutralizing monoclonal antibodies like sotrovimab, especially amid emerging variants with spike protein mutations. The study’s unique approach, comparing a monoclonal antibody with CPT, demonstrates the efficacy of early intervention using high neutralizing antibody titer CPT, even in populations with a significant proportion of elderly patients. These findings are crucial, considering the alternative treatment challenges, especially in resource-limited countries, posed by the rapidly mutating SARS-CoV-2 virus and the need for adaptable therapeutic strategies.