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Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model

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Title: Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in a COVID-19 hamster model
Authors: Sasaki, Michihito Browse this author →KAKEN DB
Sugi, Tatsuki Browse this author →KAKEN DB
Iida, Shun Browse this author →KAKEN DB
Hirata, Yuichiro Browse this author →KAKEN DB
Kusakabe, Shinji Browse this author
Konishi, Kei Browse this author
Itakura, Yukari Browse this author →KAKEN DB
Tabata, Koshiro Browse this author →KAKEN DB
Kishimoto, Mai Browse this author →KAKEN DB
Kobayashi, Hiroko Browse this author
Ariizumi, Takuma Browse this author
Intaruck, Kittiya Browse this author
Nobori, Haruaki Browse this author
Toba, Shinsuke Browse this author
Sato, Akihiko Browse this author
Matsuno, Keita Browse this author →KAKEN DB
Yamagishi, Junya Browse this author →KAKEN DB
Suzuki, Tadaki Browse this author →KAKEN DB
Hall, William W. Browse this author
Orba, Yasuko Browse this author →KAKEN DB
Sawa, Hirofumi Browse this author →KAKEN DB
Keywords: SARS-CoV-2
Antiviral therapy
Delayed treatment
Issue Date: Jan-2024
Publisher: Elsevier
Journal Title: eBioMedicine
Volume: 99
Start Page: 104950
Publisher DOI: 10.1016/j.ebiom.2023.104950
PMID: 38159532
Abstract: Background Pulmonary infection with SARS-CoV-2 stimulates host immune responses and can also result in the progression of dysregulated and critical inflammation. Throughout the pandemic, the management and treatment of COVID-19 has been continuously updated with a range of antiviral drugs and immunomodulators. Monotherapy with oral antivirals has proven to be effective in the treatment of COVID-19. However, treatment should be initiated in the early stages of infection to ensure beneficial therapeutic outcomes, and there is still room for further consideration on therapeutic strategies using antivirals. Methods We studied the therapeutic effects of monotherapy with the oral antiviral ensitrelvir or the anti-inflammatory corticosteroid methylprednisolone and combination therapy with ensitrelvir and methylprednisolone in a delayed dosing model of hamsters infected with SARS-CoV-2. Findings Combination therapy with ensitrelvir and methylprednisolone improved respiratory conditions and reduced the development of pneumonia in hamsters even when the treatment was started after 2 days post-infection. The combination therapy led to a differential histological and transcriptomic pattern in comparison to either of the monotherapies, with reduced lung damage and down-regulation of expression of genes involved in the inflammatory response. Furthermore, we found that the combination treatment is effective in case of infection with either the highly pathogenic delta or circulating omicron variants. Interpretation Our results demonstrate the advantage of combination therapy with antiviral and corticosteroid drugs in COVID-19 treatment from the perspective of lung pathology and host inflammatory responses.
Type: article
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 佐々木 道仁

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