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

• Published in: Signal transduction and targeted therapy Vol. 6; no. 1; pp. 107 - 11
• Main Authors: Lu, Yingying, Liu, Feng, Tong, Gangling, Qiu, Feng, Song, Pinhong, Wang, Xiaolin, Zou, Xiafei, Wan, Deyun, Cui, Miao, Xu, Yunsheng, Zheng, Zhihua, Hong, Peng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.03.2021; Nature Publishing Group
• Subjects: 692/699/1785; 692/699/255; 692/700/565/251; Adult; Cancer Research; Cell Biology; Coronaviruses; COVID-19; COVID-19 - diagnosis; COVID-19 - mortality; COVID-19 Drug Treatment; COVID-19 Nucleic Acid Testing; Dexamethasone - administration & dosage; Dexamethasone - agonists; Drug Synergism; Female; Humans; Interferon; Interferons - administration & dosage; Interferons - agonists; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Pathology; Retrospective Studies; SARS-CoV-2
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-021-00496-5

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% CI 1.19–2.37) and symptom relief (adjusted HR 1.48, 95% CI 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% CI 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.