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

• DOI: 10.1016/j.xcrm.2021.100287
• Publication Date: 2021-05-03T11:49:37Z
• Authors: Michael R. Filbin; Arnav Mehta; Alexis M. Schneider; Kyle R. Kays; Jamey R. Guess; Matteo Gentili; Bánk G. Fenyves; Nicole C. Charland; Anna L.K. Gonye; Irena Gushterova; Hargun K. Khanna; Thomas J. LaSalle; Kendall M. Lavin-...; Brendan M. Lilley; Carl L. Lodenstein; Kasidet Manakongt...; Justin D. Margolin; Brenna N. McKaig; Maricarmen Rojas-...; Brian C. Russo; Nihaarika Sharma; Jessica Tantivit; Molly F. Thomas; Robert E. Gerszten; Graham S. Heimberg; Paul J. Hoover; David J. Lieb; Brian Lin; Debby Ngo; Karin Pelka; Miguel Reyes; Christopher S. Sm...; Avinash Waghray; Thomas E. Wood; Amanda S. Zajac; Lori L. Jennings; Ida Grundberg; Roby P. Bhattacha...; Blair Alden Parry; Alexandra-Chloé V...; Moshe Sade-Feldman; Nir Hacohen; Marcia B. Goldberg
• Keywords: Proteome; Cell type

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