Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions

被引：183

作者：

Filbin, Michael R. ^{[1
,2
,3
]}

Mehta, Arnav ^{[3
,4
,5
,6
]}

Schneider, Alexis M. ^{[3
,7
]}

Kays, Kyle R. ^{[1
]}

Guess, Jamey R. ^{[8
]}

Gentili, Matteo ^{[3
]}

Fenyves, Bank G. ^{[1
,9
]}

Charland, Nicole C. ^{[1
]}

Gonye, Anna L. K. ^{[3
,11
]}

Gushterova, Irena ^{[3
,11
]}

Khanna, Hargun K. ^{[1
]}

LaSalle, Thomas J. ^{[3
,11
]}

Lavin-Parsons, Kendall M. ^{[1
]}

Lilley, Brendan M. ^{[1
]}

Lodenstein, Carl L. ^{[1
]}

Manakongtreecheep, Kasidet ^{[3
,10
,11
]}

Margolin, Justin D. ^{[1
]}

McKaig, Brenna N. ^{[1
]}

Rojas-Lopez, Maricarmen ^{[6
,12
,13
]}

Russo, Brian C. ^{[6
,12
,13
]}

Sharma, Nihaarika ^{[3
,11
]}

Tantivit, Jessica ^{[3
,10
,11
]}

Thomas, Molly F. ^{[3
,6
,10
,11
,14
]}

Gerszten, Robert E. ^{[6
,15
]}

Heimberg, Graham S. ^{[3
]}

Hoover, Paul J. ^{[6
,16
]}

Lieb, David J. ^{[3
]}

Lin, Brian ^{[6
,17
]}

Ngo, Debby ^{[6
,18
]}

Pelka, Karin ^{[3
]}

Reyes, Miguel ^{[3
,7
]}

Smillie, Christopher S. ^{[3
]}

Waghray, Avinash ^{[6
,17
]}

Wood, Thomas E. ^{[6
,12
,13
]}

Zajac, Amanda S. ^{[6
,12
,13
]}

Jennings, Lori L. ^{[19
]}

Grundberg, Ida ^{[8
]}

Bhattacharyya, Roby P. ^{[3
,6
,12
]}

Parry, Blair Alden ^{[1
]}

Villani, Alexandra-Chloe ^{[3
,5
,6
,10
]}

Sade-Feldman, Moshe ^{[3
,5
,6
]}

Hacohen, Nir ^{[3
,5
,6
]}

Goldberg, Marcia B. ^{[3
,6
,12
,13
,20
]}

机构：

[1] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA

[2] Harvard Med Sch, Dept Emergency Med, Boston, MA 02115 USA

[3] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[5] Massachusetts Gen Hosp, Dept Med, Canc Ctr, Boston, MA 02114 USA

[6] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[7] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[8] Olink Prote, Watertown, MA USA

[9] Semmelweis Univ, Dept Emergency Med, Budapest, Hungary

[10] Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[11] Massachusetts Gen Hosp, Dept Med, Ctr Canc Res, Boston, MA 02114 USA

[12] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA

[13] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA

[14] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA

[15] Beth Israel Deaconess Med Ctr, Dept Cardiovasc Med, CardioVasc Inst, Boston, MA 02215 USA

[16] Brigham & Womens Hosp, Dept Med, Div Rheumatol Inflammat & Immun, 75 Francis St, Boston, MA 02115 USA

[17] Massachusetts Gen Hosp, Dept Med, Ctr Regenerat Med, Boston, MA 02114 USA

[18] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA

[19] Novartis Inst BioMed Res, Cambridge, MA USA

[20] Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

来源：

CELL REPORTS MEDICINE | 2021年 / 2卷 / 05期

基金：

美国国家卫生研究院;

关键词：

MAST-CELLS; EXPRESSION; ACTIVATION; RECEPTOR; ATLAS; MILD; LUNG;

D O I：

10.1016/j.xcrm.2021.100287

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

引用

页数：23

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