Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

被引：826

作者：

Arunachalam, Prabhu S. ^{[1
]}

Wimmers, Florian ^{[1
]}

Mok, Chris Ka Pun ^{[2
]}

Perera, Ranawaka A. P. M. ^{[3
]}

Scott, Madeleine ^{[1
,4
]}

Hagan, Thomas ^{[1
]}

Sigal, Natalia ^{[1
]}

Feng, Yupeng ^{[1
]}

Bristow, Laurel ^{[5
]}

Tsang, Owen Tak-Yin ^{[6
]}

Wagh, Dhananjay ^{[7
]}

Coller, John ^{[7
]}

Pellegrini, Kathryn L. ^{[8
]}

Kazmin, Dmitri ^{[1
]}

Alaaeddine, Ghina ^{[5
]}

Leung, Wai Shing ^{[6
]}

Chan, Jacky Man Chun ^{[6
]}

Chik, Thomas Shiu Hong ^{[6
]}

Choi, Chris Yau Chung ^{[6
]}

Huerta, Christopher ^{[5
]}

McCullough, Michele Paine ^{[5
]}

Lv, Huibin ^{[2
]}

Anderson, Evan ^{[9
]}

Edupuganti, Srilatha ^{[5
]}

Upadhyay, Amit A. ^{[8
]}

Bosinger, Steve E. ^{[8
,10
]}

Maecker, Holden Terry ^{[1
]}

Khatri, Purvesh ^{[1
,4
]}

Rouphael, Nadine ^{[5
]}

Peiris, Malik ^{[2
,3
]}

Pulendran, Bali ^{[1
,11
,12
]}

机构：

[1] Stanford Univ, Inst Immun Transplantat & Infect, Sch Med, Stanford, CA 94305 USA

[2] Univ Hong Kong HKU, HKU Li Ka Shing Fac Med, Sch Publ Hlth, HKU Pasteur Res Pole, Hong Kong, Peoples R China

[3] HKU, Ctr Influenza Res, Sch Publ Hlth, HKU Li Ka Shing Fac Med, Hong Kong, Peoples R China

[4] Stanford Univ, Ctr Biomed Informat, Dept Med, Sch Med, Stanford, CA 94305 USA

[5] Emory Univ, Hope Clin Emory Vaccine Ctr, Dept Med, Div Infect Dis,Sch Med, Decatur, GA 30030 USA

[6] Hosp Author Hong Kong, Princess Margaret Hosp, Infect Dis Ctr, Hong Kong, Peoples R China

[7] Stanford Univ, Sch Med, Stanford Funct Genom Facil, Stanford, CA 94305 USA

[8] Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA

[9] Emory Univ, Dept Pediat, Div Infect Dis, Sch Med, Atlanta, GA 30322 USA

[10] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA

[11] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[12] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

来源：

SCIENCE | 2020年 / 369卷 / 6508期

基金：

中国国家自然科学基金;

关键词：

I INTERFERON; SEPSIS; CYTOKINE; RECEPTOR; DISEASE;

D O I：

10.1126/science.abc6261

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) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-alpha (IFN-alpha) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-alpha levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.

引用

页码：1210 / +

页数：52

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