Hydroxychloroquine prophylaxis and treatment is ineffective in macaque and hamster SARS-CoV-2 disease models

Rosenke, Kyle; Jarvis, Michael A.; Feldmann, Friederike; Schwarz, Benjamin; Okumura, Atsushi; Lovaglio, Jamie; Saturday, Greg; Hanley, Patrick W.; Meade-White, Kimberly; Williamson, Brandi N.; Hansen, Frederick; Perez-Perez, Lizette; Leventhal, Shanna; Tang-Huau, Tsing-Lee; Callison, Julie; Haddock, Elaine; Stromberg, Kaitlin A.; Scott, Dana; Sewell, Graham; Bosio, Catharine M.; Hawman, David; de Wit, Emmie; Feldmann, Heinz

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human COVID-19 clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies to help guide decisions. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in 2 animal disease models. The standard human malaria HCQ prophylaxis (6.5 mg/kg given weekly) and treatment (6.5 mg/kg given daily) did not significantly benefit clinical outcome, nor did it reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. Similarly, when used for prophylaxis or treatment, neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Results from these 2 preclinical animal models may prove helpful in guiding clinical use of HCQ for prophylaxis/treatment of COVID-19.