Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system.In contrast,interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids.To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity,we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids.Among patients receiving glucocorticoids,early interferon therapy was associated with earlier hospital discharge(adjusted HR 1.68,95%Cl 1.19-2.37)and symptom relief(adjusted HR 1.48;95%Cl 1.06-2.08),while these associations were insignificant among glucocorticoids nonusers.Early interferon therapy was also associated with lower prevalence of prolonged viral shedding(adjusted OR 0.24,95%Cl 0.10-0.57)only among glucocorticoids users.Additionally,these associations were glucocorticoid cumulative dose-and timing-dependent.These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.