Department of Internal Medicine, Chosun University College of Medicine, Gwangju 61452, Republic of Korea.
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Institute of Endemic Disease, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea.
Cell Rep. 2021 Oct 5;37(1):109798. doi: 10.1016/j.celrep.2021.109798. Epub 2021 Sep 20.
Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.
尽管 2019 年冠状病毒病（COVID-19）大流行对全球产生了影响，但致命性病毒性肺炎的潜在机制仍难以捉摸。在这里，我们发现与非重症病例相比，重症 COVID-19 与增强的嗜酸性粒细胞介导的炎症有关。此外，我们在重症组中证实了增强的辅助性 T 细胞（Th）2 偏向的适应性免疫反应，伴随着明显的补体激活。此外，增强的抗体反应和补体激活与疾病发病机制有关，这可以通过在来自 6 例致命病例的肺活检的气道和血管中形成免疫复合物和膜攻击复合物，以及通过在重症 COVID-19 患者的呼吸道标本中的髓样细胞中增强 Fcγ 受体（FcγR）信号和补体激活的标志性基因集特征来证明。这些结果表明，SARS-CoV-2 感染可能会引发特定的先天免疫反应，包括嗜酸性粒细胞介导的炎症，以及通过增强的 Th2 偏向免疫反应导致随后的肺部发病机制，这可能是 COVID-19 患者重症疾病的关键驱动因素。
