Cell type-specific immune dysregulation in severely ill COVID-19 patients
Cell type-specific immune dysregulation in severely ill COVID-19 patients
Abstract Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.
Aziz Adam W、Suri Harshpreet、Martins Gislaine A、Gharib Sina A、Goodridge Helen S、Matusov Yuri P、Green Chelsi ER、Yao Changfu、Bora Stephanie A、Chiang Giuliana Cerro、Patel Nayan、Chen Peter、Kassar Alexander G、Surapaneni Nirmala S、Parimon Tanyalak、Stripp Barry R、Zaman Tanzira、Suda Jo、Friedman Oren A、Palatinus Joseph A、Lopez Andres A
Women?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los AngelesWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los AngelesDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles||F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute (IBIRI), Cedars-Sinai Medical Center||Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical CenterComputational Medicine Core at Center for Lung Biology, Division of Pulmonary, Critical Care and Sleep Medicine, University of WashingtonDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles||Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los AngelesWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los AngelesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles||Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center||Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los AngelesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles||Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterWomen?ˉs Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles||Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center||Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles||Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los AngelesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles
医药卫生理论医学研究方法基础医学
Aziz Adam W,Suri Harshpreet,Martins Gislaine A,Gharib Sina A,Goodridge Helen S,Matusov Yuri P,Green Chelsi ER,Yao Changfu,Bora Stephanie A,Chiang Giuliana Cerro,Patel Nayan,Chen Peter,Kassar Alexander G,Surapaneni Nirmala S,Parimon Tanyalak,Stripp Barry R,Zaman Tanzira,Suda Jo,Friedman Oren A,Palatinus Joseph A,Lopez Andres A.Cell type-specific immune dysregulation in severely ill COVID-19 patients[EB/OL].(2025-03-28)[2025-05-18].https://www.medrxiv.org/content/10.1101/2020.07.23.20161182.点此复制
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