| 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 |
| COVID-19 |
| Antiviral therapy |
| Corticosteroid |
| Hamster |
| 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. |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/91072 |
| 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)
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