Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.
Division of Collaboration and Education, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; International Collaboration Unit, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
EBioMedicine. 2024 Jan;99:104950. doi: 10.1016/j.ebiom.2023.104950. Epub 2023 Dec 30.
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.
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.
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.
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.
Funding bodies are described in the Acknowledgments section.
SARS-CoV-2 引起的肺部感染会刺激宿主免疫反应，也可能导致失调和严重的炎症进展。在整个大流行期间，COVID-19 的管理和治疗不断更新，包括一系列抗病毒药物和免疫调节剂。口服抗病毒药物的单药治疗已被证明对 COVID-19 的治疗有效。然而，为了确保有益的治疗效果，应在感染早期开始治疗，并且对于抗病毒药物的治疗策略仍有进一步考虑的空间。
我们研究了在感染 SARS-CoV-2 的仓鼠中延迟给药模型中，口服抗病毒药物恩赛特韦或抗炎皮质类固醇甲泼尼龙单药治疗以及恩赛特韦和甲泼尼龙联合治疗的治疗效果。
即使在感染后 2 天开始治疗，恩赛特韦和甲泼尼龙联合治疗也能改善仓鼠的呼吸状况并减少肺炎的发展。与单药治疗相比，联合治疗导致了不同的组织学和转录组学模式，肺损伤减少，参与炎症反应的基因表达下调。此外，我们发现联合治疗对高致病性德尔塔或循环奥密克戎变异株感染均有效。
从肺病理学和宿主炎症反应的角度来看，我们的研究结果表明，抗病毒药物和皮质类固醇药物联合治疗 COVID-19 的优势。
资助机构在致谢部分描述。
Zotero 插件
