Dexamethasone treatment does not alter mortality but reduces pulmonary pathology in Nipah virus-infected Syrian hamsters

Abstract

Nipah virus (NiV) is an emerging zoonotic pathogen that causes severe respiratory and neurologic disease, and there are currently no licensed vaccines or approved treatments. The acute respiratory disease caused by NiV is associated with severe inflammation, similar to severe COVID-19. Dexamethasone is an affordable and widely available synthetic glucocorticoid, that improved outcomes when administered to patients with severe COVID-19. To determine whether a similar beneficial effect could be achieved during NiV infection, we tested the effect of an anti-inflammatory or immunosuppressive dose of dexamethasone on NiV in the Syrian hamster model. We found that dexamethasone treatment produced the expected hematologic changes in uninfected animals in a dose-dependent manner. In NiV-infected animals, the anti-inflammatory dose of dexamethasone reduced pulmonary pathology, while the immunosuppressive dose had no effect. The anti-inflammatory dose did not increase virus replication in tissues or virus shedding from the respiratory tract, indicating the anti-inflammatory dose of dexamethasone does not result in increased virus replication. Despite reduced lung pathology, dexamethasone treatment did not increase survival after NiV challenge. When dexamethasone treatment was combined with the antiviral remdesivir, dexamethasone negated the increased survival observed in hamsters treated with remdesivir alone. Our study provides critical information on the effect of dexamethasone administration on the outcome of NiV infection and cautions against the use of dexamethasone in combination with other antivirals like remdesivir without preclinical validation.