Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia

被引：78

作者：

Kreutmair, Stefanie ^{[1
,2
,3
]}

Unger, Susanne ^{[1
]}

Nunez, Nicolas Gonzalo ^{[1
]}

Ingelfinger, Florian ^{[1
]}

Alberti, Chiara ^{[1
]}

De Feo, Donatella ^{[1
]}

Krishnarajah, Sinduya ^{[1
]}

Kauffmann, Manuel ^{[1
]}

Friebel, Ekaterina ^{[1
]}

Babaei, Sepideh ^{[4
]}

Gaborit, Benjamin ^{[5
]}

Lutz, Mirjam ^{[1
]}

Jurado, Nicole Puertas ^{[1
]}

Malek, Nisar P. ^{[4
]}

Goepel, Siri ^{[4
,6
]}

Rosenberger, Peter ^{[7
]}

Haeberle, Helene A. ^{[7
]}

Ayoub, Ikram ^{[8
]}

Al-Hajj, Sally ^{[8
]}

Nilsson, Jakob ^{[9
]}

Claassen, Manfred ^{[4
]}

Liblau, Roland ^{[8
]}

Martin-Blondel, Guillaume ^{[8
,10
]}

Bitzer, Michael ^{[4
]}

Roquilly, Antoine ^{[5
]}

Becher, Burkhard ^{[1
]}

机构：

[1] Univ Zurich, Inst Expt Immunol, CH-8057 Zurich, Switzerland

[2] German Canc Consortium DKTK, D-79106 Freiburg, Germany

[3] German Canc Res Ctr, Partner Site Freiburg, D-79106 Freiburg, Germany

[4] Eberhard Karls Univ Tubingen, Dept Internal Med 1, D-72076 Tubingen, Germany

[5] Univ Nantes, Serv Anesthesie Reanimat Chirurg, CHU Nantes, Pole Anesthesie Reanimat, F-44093 Nantes, France

[6] German Ctr Infect Res DZIF, Partner Site Tuebingen, D-72076 Tubingen, Germany

[7] Eberhard Karls Univ Tubingen, Dept Anesthesiol & Intens Care Med, D-72076 Tubingen, Germany

[8] Univ Toulouse, CNRS, Toulouse Inst Infect & Inflammatory Dis, Inst Natl Sante & Rech Med,UPS, F-31024 Toulouse, France

[9] Univ Hosp Zurich, Dept Immunol, CH-8006 Zurich, Switzerland

[10] Toulouse Univ Hosp, Dept Infect & Trop Dis, F-31059 Toulouse, France

来源：

IMMUNITY | 2021年 / 54卷 / 07期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

T-CELLS; INFECTION; CYTOMETRY; RESPONSES; IMMUNE; MILD;

D O I：

10.1016/j.immuni.2021.05.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Immune profiling of COVID-19 patients has identified numerous alterations in both innate and adaptive immunity. However, whether those changes are specific to SARS-CoV-2 or driven by a general inflammatory response shared across severely ill pneumonia patients remains unknown. Here, we compared the immune profile of severe COVID-19 with non-SARS-CoV-2 pneumonia ICU patients using longitudinal, high-dimensional single-cell spectral cytometry and algorithm-guided analysis. COVID-19 and non-SARS-CoV-2 pneumonia both showed increased emergency myelopoiesis and displayed features of adaptive immune paralysis. However, pathological immune signatures suggestive of T cell exhaustion were exclusive to COVID-19. The integration of single-cell profiling with a predicted binding capacity of SARS-CoV-2 peptides to the patients' HLA profile further linked the COVID-19 immunopathology to impaired virus recognition. Toward clinical translation, circulating NKT cell frequency was identified as a predictive biomarker for patient outcome. Our comparative immune map serves to delineate treatment strategies to interfere with the immunopathologic cascade exclusive to severe COVID-19.

引用

页码：1578 / +

页数：21

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