Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

被引：2138

作者：

Hadjadj, Jerome ^{[1
,2
]}

Yatim, Nader ^{[2
,3
]}

Barnabei, Laura ^{[1
]}

Corneau, Aurelien ^{[4
]}

Boussier, Jeremy ^{[3
]}

Smith, Nikaia ^{[3
]}

Pere, Helene ^{[5
,6
]}

Charbit, Bruno ^{[7
]}

Bondet, Vincent ^{[3
]}

Chenevier-Gobeaux, Camille ^{[8
]}

Breillat, Paul ^{[2
]}

Carlier, Nicolas ^{[9
]}

Gauzit, Remy ^{[10
]}

Morbieu, Caroline ^{[2
]}

Pene, Frederic ^{[11
,12
]}

Marin, Nathalie ^{[12
]}

Roche, Nicolas ^{[9
,11
]}

Szwebel, Tali-Anne ^{[2
]}

Merkling, Sarah H. ^{[13
]}

Treluyer, Jean-Marc ^{[14
,15
]}

Veyer, David ^{[6
,16
,17
]}

Mouthon, Luc ^{[2
,11
]}

Blanc, Catherine ^{[4
]}

Tharaux, Pierre-Louis ^{[5
]}

Rozenberg, Flore ^{[11
,18
]}

Fischer, Alain ^{[1
,19
,20
]}

Duffy, Darragh ^{[3
,7
]}

Rieux-Laucat, Frederic ^{[1
]}

Kerneis, Solen ^{[10
,21
,22
]}

Terrier, Benjamin ^{[2
,5
]}

机构：

[1] Univ Paris, Lab Immunogenet Pediat Autoimmune Dis, Imagine Inst, INSERM UMR 1163, F-75015 Paris, France

[2] Hop Cochin, AP HP, Natl Reference Ctr Rare Syst Autoimmune Dis, APHP CUP,Dept Internal Med, F-75014 Paris, France

[3] Inst Pasteur, Dept Immunol, Lab Dendrit Cell Immunobiol, INSERM U1223, F-75015 Paris, France

[4] Sorbonne Univ, PASS, UMS037, Plateforme Cytometrie Pitie Salpetriere CyPS, F-75013 Paris, France

[5] Univ Paris, PARCC, U970, INSERM, F-75015 Paris, France

[6] Hop Europeen Georges Pompidou, AP HP, APHP CUP, Serv Microbiol, F-75015 Paris, France

[7] Inst Pasteur, CRT, Cytometry & Biomarkers UTechS, F-75015 Paris, France

[8] Hop Cochin, AP HP, APHP CUP, Dept Automated Diagnost Biol, F-75014 Paris, France

[9] Hop Cochin, AP HP, APHP CUP, Dept Pulmonol, F-75014 Paris, France

[10] Hop Cochin, AP HP, APHP CUP, Equipe Mobile Infectiol, F-75014 Paris, France

[11] Univ Paris, Inst Cochin, CNRS UMR8104, INSERM U1016, F-75006 Paris, France

[12] Hop Cochin, AP HP, APHP CUP, Serv Med Intens & Reanimat, F-75014 Paris, France

[13] Inst Pasteur, Insect Virus Interact Unit, CNRS, UMR 2000, Paris, France

[14] Univ Paris, Pharmacol & Evaluat Therapeut Chez Enfant & Femme, F-75006 Paris, France

[15] Hop Cochin Necker, AP HP, APHP CUP, Rech Clin & Pharmacol, F-75014 Paris, France

[16] Univ Paris, F-75006 Paris, France

[17] Sorbonne Univ, Ctr Rech Cordeliers, Funct Genom Solid Tumors FunGeST, INSERM, F-75006 Paris, France

[18] Hop Cochin, AP HP, APHP CUP, Serv Virol, F-75014 Paris, France

[19] Hop Necker Enfants Malad, AP HP, APHP CUP, Dept Paediat Immunohaematol & Rheumatol, F-75015 Paris, France

[20] Coll France, Paris, France

[21] Univ Paris, IAME, INSERM, F-75006 Paris, France

[22] Inst Pasteur, Epidemiol & Modelling Antibiot Evas EMAE, F-75015 Paris, France

来源：

SCIENCE | 2020年 / 369卷 / 6504期

关键词：

CORONAVIRUS;

D O I：

10.1126/science.abc6027

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-beta and low IFN-alpha production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-kappa B and characterized by increased tumor necrosis factor-alpha and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

引用

页码：718 / +

页数：42

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