Liechti Thomas, Iftikhar Yaser, Mangino Massimo, Beddall Margaret, Goss Charles W, O'Halloran Jane A, Mudd Philip, Roederer Mario
ImmunoTechnology Section, Vaccine Research Center, NIAID, NIH, USA, 20892.
Department of Twin Research & Genetic Epidemiology, King's College of London, London, UK.
Res Sq. 2022 Mar 10:rs.3.rs-1378671. doi: 10.21203/rs.3.rs-1378671/v1.
Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measured the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 showed reduced frequencies of T cell, MAIT cell and dendritic cell (DCs) subsets and altered chemokine receptor expression on several subsets, such as reduced levels of CCR1 and CCR2 on monocyte subsets. Furthermore, we found reduced frequencies of type I interferon-producing plasmacytoid DCs and altered IFNAR2 expression on several myeloid cells in individuals recovered from severe COVID-19. Thus, these data identify potential immune mechanisms contributing to severe COVID-19.
重症新型冠状病毒肺炎（COVID-19）会引发严重的免疫紊乱，但导致重症COVID-19的感染前免疫特征仍不清楚。全基因组关联研究（GWAS）确定了重症疾病与几种趋化因子受体以及I型干扰素途径中的分子之间存在密切关联。在此，我们使用高维流式细胞术定义了与重症COVID-19相关的免疫特征。我们测量了从轻度、中度、重度或危重症COVID-19中康复的个体的外周免疫系统，并且只关注那些恢复到稳态的免疫特征。患有重症COVID-19的个体表现出T细胞、黏膜相关恒定T细胞（MAIT细胞）和树突状细胞（DCs）亚群的频率降低，并且几个亚群上的趋化因子受体表达发生改变，例如单核细胞亚群上CCR1和CCR2水平降低。此外，我们发现从重症COVID-19中康复的个体中，产生I型干扰素的浆细胞样DCs频率降低，并且几种髓样细胞上的IFNAR2表达发生改变。因此，这些数据确定了导致重症COVID-19的潜在免疫机制。
