Biophytis, Sorbonne Université, Paris, France.
Biophytis Inc., Cambridge, MA, USA.
Emerg Microbes Infect. 2021 Dec;10(1):2256-2263. doi: 10.1080/22221751.2021.2006579.
Since December 2019, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has changed our lives. Elderly and those with comorbidities represent the vast majority of patients hospitalized with severe COVID-19 symptoms, including acute respiratory disease syndrome and cardiac dysfunction. Despite a huge effort of the scientific community, improved treatment modalities limiting the severity and mortality of hospitalized COVID-19 patients are still required. Here, we compare the effectiveness of virus- and patients-centred strategies to reduce COVID-19 mortality. We also discuss the therapeutic options that might further reduce death rates associated with the disease in the future. Unexpectedly, extensive review of the literature suggests that SARS-CoV-2 viral load seems to be associated neither with the severity of symptoms nor with mortality of hospitalized patients with COVID-19. This may explain why, so far, virus-centred strategies using antivirals aiming to inhibit the viral replicative machinery have failed to reduce COVID-19 mortality in patients with respiratory failure. By contrast, anti-inflammatory treatments without antiviral capacities but centred on patients, such as dexamethasone or Tocilizumab, reduce COVID-19 mortality. Finally, since the spike protein of SARS-CoV-2 binds to angiotensin converting enzyme 2 and inhibits its function, we explore the different treatment options focussing on rebalancing the renin-angiotensin system. This new therapeutic strategy could hopefully further reduce the severity of respiratory failure and limit COVID-19 mortality in elderly patients.
自 2019 年 12 月以来,由严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染引起的 2019 年冠状病毒病(COVID-19)改变了我们的生活。患有严重 COVID-19 症状(包括急性呼吸窘迫综合征和心功能障碍)住院的患者绝大多数为老年患者和合并症患者。尽管科学界做出了巨大努力,但仍需要改进治疗方式来限制住院 COVID-19 患者的严重程度和死亡率。在这里,我们比较了以病毒和患者为中心的策略来降低 COVID-19 的死亡率。我们还讨论了未来可能进一步降低与该疾病相关死亡率的治疗选择。出乎意料的是,广泛的文献回顾表明,SARS-CoV-2 病毒载量似乎既与症状的严重程度无关,也与 COVID-19 住院患者的死亡率无关。这也许可以解释为什么迄今为止,旨在抑制病毒复制机制的抗病毒药物为中心的病毒策略未能降低呼吸衰竭患者的 COVID-19 死亡率。相比之下,以患者为中心、无抗病毒作用但具有抗炎作用的治疗方法,如地塞米松或托珠单抗,可降低 COVID-19 的死亡率。最后,由于 SARS-CoV-2 的刺突蛋白与血管紧张素转换酶 2 结合并抑制其功能,我们探讨了以重新平衡肾素-血管紧张素系统为中心的不同治疗选择。这种新的治疗策略有望进一步降低呼吸衰竭的严重程度,并限制老年患者的 COVID-19 死亡率。