Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-Monitored Challenge Model of COVID-19 in Healthy Volunteers

Levine, Myron M; Abdullah, Salim; Arabi, Yaseen M; Darko, Delese Mimi; Durbin, Anna P; Estrada, Vicente; Jamrozik, Euzebiusz; Kremsner, Peter G; Lagos, Rosanna; Pitisuttithum, Punnee; Plotkin, Stanley A; Sauerwein, Robert; Shi, Sheng-Li; Sommerfelt, Halvor; Subbarao, Kanta; Treanor, John J; Vrati, Sudhanshu; King, Deborah; Balasingam, Shobana; Weller, Charlie; Aguilar, Anastazia Older; Cassetti, M Cristina; Krause, Philip R; Restrepo, Ana Maria Henao

WHO convened an Advisory Group (AG) to consider the feasibility, potential value and limitations of establishing a closely-monitored challenge model of experimental SARS-CoV-2 infection and COVID-19 in healthy adult volunteers. The AG included experts in design, establishment and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (SARS-CoV-2’s potential to cause severe/fatal illness, its high transmissibility, and lack of a “rescue treatment” to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.