Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment

Iwanami, S.; Ejima, K.; Kim, K. S.; Noshita, K.; Fujita, Y.; Miyazaki, T.; Kohno, S.; Miyazaki, Y.; Morimoto, S.; Nakaoka, S.; Koizumi, Y.; Asai, Y.; Aihara, K.; Watashi, K.; Thompson, R. N.; Shibuya, K.; Fujiu, K.; Perelson, A. S.; Shingo, I.; Wakita, T.

Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.