Extended Data Fig. 1: Comparison of COVID-19 parameters and response to therapeutics in human patients, humanized mice and other animal models.

Although substantial anti-viral immunity mediates viral clearance in non-severe COVID-19², robust inflammatory cytokine production, decreased circulating lymphocytes and failure to generate germinal centers characterizes the immunopathology in severe COVID-19^2,3,4. Dysregulated myeloid^5,6,7,8 and lymphocyte^{9,10,11,12,53} compartments, including monocytes, macrophages, neutrophils, NK cells and antibody secreting B cells, have been described as players in the observed lung immunopathology of COVID-19. Accurate model systems are essential to rapidly evaluate promising discoveries but most models currently available in mice, ferrets and hamsters do not recapitulate sustained immunopathology described in COVID-19 patients. The following table summarizes various aspects of the human disease and how well these are recapitulated in existing animal models of COVID-19 and in our humanized mouse model of COVID-19. Additional work cited: refs. ^{87,88,89,90,91}.