• Zi-Wei Ye, Shuofeng Yuan, Jasper Fuk-Woo Chan, Anna Jinxia Zhang, Ching-Yun Yu, Chon Phin Ong, Dong Yang, Chris Chun-Yiu Chan, Kaiming Tang, Jianli Cao, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Jian-Piao Cai, Hin Chu, Kwok-Yung Yuen, and Dong-Yan Jin.
• State Key Laboratory of Emerging Infectious Diseases and Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.
• Emerg Microbes Infect. 2021 Dec 1; 10 (1): 291-304.

AbstractEffective 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.

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