The Royal London Hospital, London, UK.
Centre for Clinical Pharmacology and Therapeutics, UCL, London, UK.
Br J Clin Pharmacol. 2021 Mar;87(3):845-857. doi: 10.1111/bcp.14540. Epub 2020 Oct 14.
Host immunity is required to clear SARS-CoV-2, and inability to clear the virus because of host or pathogen factors renders those infected at risk of poor outcomes. Estimates of those who are able to clear the virus with asymptomatic or paucisymptomatic COVID-19 remain unclear, and dependent on widespread testing. However, evidence is emerging that in severe cases, pathological mechanisms of hyperinflammation and coagulopathy ensue, the former supported by results from the RECOVERY trial demonstrating a reduction in mortality with dexamethasone in advanced COVID-19. It remains unclear whether these pathogenic pathways are secondary to a failure to clear the virus because of maladaptive immune responses or if these are sequential COVID-19 defining illnesses. Understanding the pathophysiological mechanisms underpinning these cascades is essential to formulating rationale therapeutic approaches beyond the use of dexamethasone. Here, we review the pathophysiology thought to underlie COVID-19 with clinical correlates and the current therapeutic approaches being investigated.
宿主免疫是清除 SARS-CoV-2 的必要条件，由于宿主或病原体因素而无法清除病毒，使得感染者面临不良结局的风险。那些能够无症状或轻症 COVID-19 清除病毒的人的估计仍然不清楚，并且取决于广泛的检测。然而，有证据表明，在严重情况下，会出现过度炎症和凝血功能障碍的病理机制，前者得到了 RECOVERY 试验的结果支持，该试验表明在晚期 COVID-19 中使用地塞米松可降低死亡率。目前尚不清楚这些致病途径是由于适应性免疫反应失败而无法清除病毒的结果，还是 COVID-19 相继发生的疾病。了解这些级联反应背后的病理生理学机制对于制定合理的治疗方法至关重要，而不仅仅是使用地塞米松。在这里，我们回顾了 COVID-19 的病理生理学基础及其与临床相关性以及目前正在研究的治疗方法。
