Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin, China.
Clin Microbiol Rev. 2022 Apr 20;35(2):e0018821. doi: 10.1128/cmr.00188-21. Epub 2022 Feb 2.
The lung is the primary site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced immunopathology whereby the virus enters the host cells by binding to angiotensin-converting enzyme 2 (ACE2). Sophisticated regeneration and repair programs exist in the lungs to replenish injured cell populations. However, known resident stem/progenitor cells have been demonstrated to express ACE2, raising a substantial concern regarding the long-term consequences of impaired lung regeneration after SARS-CoV-2 infection. Moreover, clinical treatments may also affect lung repair from antiviral drug candidates to mechanical ventilation. In this review, we highlight how SARS-CoV-2 disrupts a program that governs lung homeostasis. We also summarize the current efforts of targeted therapy and supportive treatments for COVID-19 patients. In addition, we discuss the pros and cons of cell therapy with mesenchymal stem cells or resident lung epithelial stem/progenitor cells in preventing post-acute sequelae of COVID-19. We propose that, in addition to symptomatic treatments being developed and applied in the clinic, targeting lung regeneration is also essential to restore lung homeostasis in COVID-19 patients.
肺是严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)引起免疫病理的主要部位,病毒通过与血管紧张素转换酶 2(ACE2)结合进入宿主细胞。肺部存在复杂的再生和修复程序,以补充受损的细胞群体。然而,已知的固有干细胞/祖细胞已被证明表达 ACE2,这引起了人们对 SARS-CoV-2 感染后肺再生受损的长期后果的极大关注。此外,临床治疗也可能影响抗病毒药物候选物到机械通气的肺修复。在这篇综述中,我们强调了 SARS-CoV-2 如何破坏控制肺内稳态的程序。我们还总结了针对 COVID-19 患者的靶向治疗和支持性治疗的最新进展。此外,我们还讨论了间充质干细胞或固有肺上皮干细胞/祖细胞在预防 COVID-19 后急性后遗症方面的细胞治疗的优缺点。我们提出,除了正在开发和应用于临床的对症治疗外,靶向肺再生对于恢复 COVID-19 患者的肺内稳态也至关重要。