Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19).
Bo Diao,Chenhui Wang,Yingjun Tan,Xiewan Chen,Ying Liu,Lifen Ning,Li Chen,Min Li,Yueping Liu,Gang Wang,Zilin Yuan,Zeqing Feng,Yi Zhang,Yuzhang Wu,Yongwen Chen +14 more
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T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted, and non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms.Abstract:
Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.read more
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Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
Miriam Merad,Jerome Martin +1 more
TL;DR: The potentially pathological roles of macrophages during SARS-CoV-2 infection are described and ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19 are discussed.
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Nicolas Vabret,Graham J. Britton,Conor Gruber,Samarth Hegde,Joel Kim,Maria Kuksin,Rachel Levantovsky,Louise Malle,Alvaro Moreira,Matthew D. Park,Luisanna Pia,Emma Risson,Miriam Saffern,Bérengère Salomé,Myvizhi Esai Selvan,Matthew P. Spindler,Jessica Tan,Verena van der Heide,Jill Gregory,Konstantina Alexandropoulos,Nina Bhardwaj,Brian D. Brown,Benjamin Greenbaum,Zeynep H. Gümüş,Dirk Homann,Amir Horowitz,Alice O. Kamphorst,Maria A. Curotto de Lafaille,Saurabh Mehandru,Miriam Merad,Robert M. Samstein,Manasi Agrawal,Mark Aleynick,Meriem Belabed,Matthew Brown,Maria Casanova-Acebes,Jovani Catalan,Monica Centa,Andrew Charap,Andrew K Chan,Steven T. Chen,Jonathan Chung,Cansu Cimen Bozkus,Evan Cody,Francesca Cossarini,Erica Dalla,Nicolas F. Fernandez,John A. Grout,Dan Fu Ruan,Pauline Hamon,Etienne Humblin,Divya Jha,Julia Kodysh,Andrew Leader,Matthew Lin,Katherine E. Lindblad,Daniel Lozano-Ojalvo,Gabrielle Lubitz,Assaf Magen,Zafar Mahmood,Gustavo Martinez-Delgado,Jaime Mateus-Tique,Elliot Meritt,Chang Moon,Justine Noel,Timothy O'Donnell,Miyo Ota,Tamar Plitt,Venu Pothula,Jamie Redes,Ivan Reyes Torres,Mark P. Roberto,Alfonso R. Sanchez-Paulete,Joan Shang,Alessandra Soares Schanoski,Maria Suprun,Michelle Tran,Natalie Vaninov,C. Matthias Wilk,Julio A. Aguirre-Ghiso,Dusan Bogunovic,Judy H. Cho,Jeremiah J. Faith,Emilie K. Grasset,Peter S. Heeger,Ephraim Kenigsberg,Florian Krammer,Uri Laserson +87 more
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.
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Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications
Divij Mathew,Josephine R. Giles,Amy E. Baxter,Derek A. Oldridge,Allison R. Greenplate,Jennifer E. Wu,Cécile Alanio,Leticia Kuri-Cervantes,M. Betina Pampena,Kurt D'Andrea,Sasikanth Manne,Zeyu Chen,Yinghui Jane Huang,John P. Reilly,Ariel R. Weisman,Caroline A. G. Ittner,Oliva Kuthuru,Jeanette Dougherty,Kito Nzingha,Nicholas Han,Justin Kim,Ajinkya Pattekar,Eileen C. Goodwin,Elizabeth M. Anderson,Madison E. Weirick,Sigrid Gouma,Claudia P. Arevalo,Marcus J. Bolton,Fang Chen,Simon F. Lacey,Holly Ramage,Sara Cherry,Scott E. Hensley,Sokratis A. Apostolidis,Alexander C. Huang,Laura A. Vella,Laura A. Vella,Michael R. Betts,Nuala J. Meyer,E. John Wherry +39 more
TL;DR: High-dimensional flow cytometry of hospitalized COVID-19 patients found three prominent and distinct immunotypes that are related to disease severity and clinical parameters, and a compendium of immune cell information and roadmaps for potential therapeutic interventions is provided.
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A single-cell atlas of the peripheral immune response in patients with severe COVID-19.
Aaron J. Wilk,Arjun Rustagi,Nancy Q. Zhao,Jonasel Roque,Giovanny J Martínez-Colón,Julia L. McKechnie,Geoffrey T. Ivison,Thanmayi Ranganath,Rosemary Vergara,Taylor Mi Hollis,Laura J. Simpson,Philip M. Grant,Aruna Subramanian,Albert J. Rogers,Catherine A. Blish +14 more
TL;DR: Single-cell transcriptomic analysis identifies changes in peripheral immune cells in seven hospitalized patients with COVID-19, including HLA class II downregulation, a heterogeneous interferon-stimulated gene signature and low pro-inflammatory cytokine gene expression in monocytes and lymphocytes.
Journal ArticleDOI
SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.
Julian Braun,Lucie Loyal,Marco Frentsch,Daniel Wendisch,Philipp Georg,Florian Kurth,Florian Kurth,Stefan Hippenstiel,Manuela Dingeldey,Beate Kruse,Florent Fauchere,Emre Baysal,Maike Mangold,Larissa Henze,Roland Lauster,Roland Lauster,Marcus A. Mall,Marcus A. Mall,Kirsten Beyer,Jobst Röhmel,Sebastian Voigt,Jürgen Schmitz,Stefan Miltenyi,Ilja Demuth,Marcel A. Müller,Andreas C. Hocke,Martin Witzenrath,Norbert Suttorp,Florian Kern,Ulf Reimer,Holger Wenschuh,Christian Drosten,Victor M. Corman,Claudia Giesecke-Thiel,Leif E. Sander,Andreas Thiel +35 more
TL;DR: CD4 + T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and healthy donors are found, indicating that spike-protein cross-reactive T cells are present and probably generated during previous encounters with endemic coronaviruses.
References
More filters
Journal ArticleDOI
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Wenbo Xu,Guizhen Wu,George F. Gao,Wenjie Tan +18 more
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Journal ArticleDOI
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Journal ArticleDOI
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
Dawei Wang,Bo Hu,Chang Hu,Fangfang Zhu,Xing Liu,Jing Zhang,Binbin Wang,Hui Xiang,Zhenshun Cheng,Yong Xiong,Yan Zhao,Yirong Li,Xinghuan Wang,Zhiyong Peng +13 more
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Journal ArticleDOI
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Nanshan Chen,Min Zhou,Xuan Dong,Jie-Ming Qu,Fengyun Gong,Yang Han,Yang Qiu,Jingli Wang,Ying Liu,Yuan Wei,Jia'an Xia,Ting Yu,Xinxin Zhang,Li Zhang +13 more
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
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