Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers
Levine MM., Abdullah S., Arabi YM., Darko DM., Durbin AP., Estrada V., Jamrozik E., Kremsner PG., Lagos R., Pitisuttithum P., Plotkin SA., Sauerwein R., Shi S-L., Sommerfelt H., Subbarao K., Treanor JJ., Vrati S., King D., Balasingam S., Weller C., Aguilar AO., Cassetti MC., Krause PR., Restrepo AMH.
Abstract WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (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 (the potential of SARS-CoV-2 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.