Clinical and pathological investigation of severe COVID-19 patients.

Li, Shaohua; Jiang, Lina; Li, Xi; Lin, Fang; Wang, Yijin; Li, Boan; Jiang, Tianjun; An, Weimin; Liu, Shuhong; Liu, Hongyang; Xu, Pengfei; Zhao, Lihua; Zhang, Lixin; Mu, Jinsong; Wang, Hongwei; Kang, Jiarui; Li, Yan; Huang, Lei; Zhu, Caizhong; Zhao, Shousong; Lu, Jiangyang; Ji, Junsheng; Zhao, Jingmin

BACKGROUND Severe acute respiratory coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) has become a pandemic. This study addressed the clinical and immunopathological characteristics of severe COVID-19. METHODS Sixty-nine COVID-19 patients were classified into as severe and non-severe groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from two deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS Circulating cytokines, including IL8, IL6, TNFα, IP10, MCP1, and RANTES, were significantly elevated in severe COVID-19 patients. Dynamic IL6 and IL8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both SARS-CoV-2 caused cytopathy and immunopathologic damage. Strategies that encourage pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of severe COVID-19 patients.