Beneficial effect of combinational methylprednisolone and remdesivir in hamster model of SARS-CoV-2 infection

• Published in: Emerging microbes & infections Vol. 10; no. 1; pp. 291 - 304
• Main Authors: Ye, Zi-Wei, Yuan, Shuofeng, Chan, Jasper Fuk-Woo, Zhang, Anna Jinxia, Yu, Ching-Yun, Ong, Chon Phin, Yang, Dong, Chan, Chris Chun-Yiu, Tang, Kaiming, Cao, Jianli, Poon, Vincent Kwok-Man, Chan, Chris Chung-Sing, Cai, Jian-Piao, Chu, Hin, Yuen, Kwok-Yung, Jin, Dong-Yan
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-01-2021; Taylor & Francis Group
• Subjects: Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - pharmacology; Adenosine Monophosphate - therapeutic use; Alanine - analogs & derivatives; Alanine - pharmacology; Alanine - therapeutic use; Animals; Antibodies, Viral - blood; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; combination therapy; Coronaviruses; corticosteroid; COVID-19; COVID-19 - drug therapy; COVID-19 - pathology; COVID-19 - virology; Cytokines - biosynthesis; Cytokines - immunology; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Macrophages - immunology; Macrophages - virology; Male; Mesocricetus; Methylprednisolone - pharmacology; Methylprednisolone - therapeutic use; remdesivir; Respiratory System - pathology; Respiratory System - virology; RNA, Viral; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Spike Glycoprotein, Coronavirus - immunology; Viral Load - drug effects; Virus Replication - drug effects; COVID-19; corticosteroid; combination therapy; SARS-CoV-2; remdesivir
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2021.1885998

Effective treatments for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Dexamethasone has been shown to confer survival benefits to certain groups of hospitalized patients, but whether glucocorticoids such as dexamethasone and methylprednisolone should be used together with antivirals to prevent a boost of SARS-CoV-2 replication remains to be determined. Here, we show the beneficial effect of methylprednisolone alone and in combination with remdesivir in the hamster model of SARS-CoV-2 infection. Treatment with methylprednisolone boosted RNA replication of SARS-CoV-2 but suppressed viral induction of proinflammatory cytokines in human monocyte-derived macrophages. Although methylprednisolone monotherapy alleviated body weight loss as well as nasal and pulmonary inflammation, viral loads increased and antibody response against the receptor-binding domain of spike protein attenuated. In contrast, a combination of methylprednisolone with remdesivir not only prevented body weight loss and inflammation, but also dampened viral protein expression and viral loads. In addition, the suppressive effect of methylprednisolone on antibody response was alleviated in the presence of remdesivir. Thus, combinational anti-inflammatory and antiviral therapy might be an effective, safer and more versatile treatment option for COVID-19. These data support testing of the efficacy of a combination of methylprednisolone and remdesivir for the treatment of COVID-19 in randomized controlled clinical trials.