ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to humanity. SARS-CoV-2 invades host cells, causing a failure of host immune recognition. Instead of an effective antiviral immunological response after SARS-CoV-2 invasion, the cascading pathological syndrome of COVID-19, especially in severe disease, is exacerbated by an overt inflammatory response and the suppression of SARS-CoV-2–specific immune responses. As is known, excessive inflammation leads to pathophysiological changes in virus-infected tissues or organs, manifested by imbalanced immune responses, cytokine storm, and aggressive neutrophil activation, ultimately leading to lung damage, such as alveolar damage, endotheliitis, and fluid overload. However, the triggers and consequences of a disruption to immune system homeostasis and the underlying mechanisms of uncontrolled immunopathology following viral infection remain unclear. Here, we review the dynamic and systemic immune progression from an imbalance in cell-mediated immune responses to COVID-19 lung injury. Our understanding of key mechanisms involved in pathogenesis is critical for the development of therapeutic agents and to optimize therapeutic strategies.

摘要

由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的 2019 年冠状病毒病 (COVID-19) 大流行对人类构成迫在眉睫的威胁。SARS-CoV-2 侵入宿主细胞，导致宿主免疫识别失败。SARS-CoV-2 入侵后没有有效的抗病毒免疫反应，而是 COVID-19 的级联病理综合征，尤其是在严重疾病中，会因明显的炎症反应和 SARS-CoV-2 特异性免疫反应的抑制而加剧。众所周知，过度炎症会导致病毒感染的组织或器官发生病理生理变化，表现为免疫反应失衡、细胞因子风暴和中性粒细胞侵袭性激活，最终导致肺损伤，如肺泡损伤、内皮炎和体液超负荷。然而，免疫系统稳态破坏的触发因素和后果以及病毒感染后不受控制的免疫病理学的潜在机制仍不清楚。在这里，我们回顾了从细胞介导的免疫反应失衡到 COVID-19 肺损伤的动态和全身免疫进展。我们对参与发病机制的关键机制的理解对于治疗药物的开发和优化治疗策略至关重要。