Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

被引：906

作者：

Mathew, Divij ^{[1
,2
]}

Giles, Josephine R. ^{[1
,2
,3
]}

Baxter, Amy E. ^{[1
,2
]}

Oldridge, Derek A. ^{[1
,4
]}

Greenplate, Allison R. ^{[1
,2
]}

Wu, Jennifer E. ^{[1
,2
,3
]}

Alanio, Cecile ^{[1
,2
,3
]}

Kuri-Cervantes, Leticia ^{[1
,5
]}

Pampena, M. Betina ^{[1
,5
]}

D'Andrea, Kurt ^{[6
]}

Manne, Sasikanth ^{[1
,2
]}

Chen, Zeyu ^{[1
,2
]}

Huang, Yinghui Jane ^{[1
,2
]}

Reilly, John P. ^{[7
]}

Weisman, Ariel R. ^{[7
]}

Ittner, Caroline A. G. ^{[7
]}

Kuthuru, Oliva ^{[1
,2
]}

Dougherty, Jeanette ^{[1
,2
]}

Nzingha, Kito ^{[1
,2
]}

Han, Nicholas ^{[1
,2
]}

Kim, Justin ^{[1
,2
]}

Pattekar, Ajinkya ^{[1
,8
]}

Goodwin, Eileen C. ^{[1
,5
]}

Anderson, Elizabeth M. ^{[1
,5
]}

Weirick, Madison E. ^{[1
,5
]}

Gouma, Sigrid ^{[1
,5
]}

Arevalo, Claudia P. ^{[1
,5
]}

Bolton, Marcus J. ^{[1
,5
]}

Chen, Fang ^{[9
]}

Lacey, Simon F. ^{[4
,9
]}

Ramage, Holly ^{[10
]}

Cherry, Sara ^{[1
,4
]}

Hensley, Scott E. ^{[1
,5
]}

Apostolidis, Sokratis A. ^{[1
,11
]}

Huang, Alexander C. ^{[1
,3
,12
]}

Vella, Laura A. ^{[1
,13
]}

Betts, Michael R. ^{[1
,5
]}

Meyer, Nuala J. ^{[14
]}

Wherry, E. John ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA

[3] Univ Penn, Parker Inst Canc Immunotherapy, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Div Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Univ Penn, Div Pulm Allergy & Crit Care Med, Perelman Sch Med, Ctr Translat Lung Biol,Lung Biol Inst,Dept Med, Philadelphia, PA 19104 USA

[8] Univ Penn, Div Gastroenterol, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[9] Univ Penn, Ctr Cellular Immunotherapies, Perelman Sch Med, Philadelphia, PA 19104 USA

[10] Thomas Jefferson Univ, Dept Microbiol, Philadelphia, PA 19107 USA

[11] Univ Penn, Perelman Sch Med, Div Rheumatol, Dept Med, Philadelphia, PA 19104 USA

[12] Univ Penn, Perelman Sch Med, Div Hematol & Oncol, Dept Med, Philadelphia, PA 19104 USA

[13] Childrens Hosp Philadelphia, Div Infect Dis, Dept Pediat, Philadelphia, PA 19104 USA

[14] Univ Penn, Dept Med, Div Pulm & Crit Care Med, Perelman Sch Med, Philadelphia, PA 19104 USA

来源：

SCIENCE | 2020年 / 369卷 / 6508期

关键词：

VIRUS-INFECTION; T-CELLS; RESPONSES; FEVER;

D O I：

10.1126/science.abc8511

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 currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of similar to 200 immune and similar to 50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

引用

页码：1209 / +

页数：42

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