Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions.

BioRxiv : the Preprint Server for Biology
Divij MathewE John Wherry

Abstract

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three "immunotypes" associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.

Citations

Jun 7, 2020·Nature Reviews. Immunology·Samarth Hegde
Aug 23, 2020·Journal of Clinical Immunology·Lucie Rodriguez, Petter Brodin
Oct 3, 2020·Nutrients·Kashaf JunaidAbdul Rehman
Jul 17, 2020·Science Immunology·Leticia Kuri-CervantesMichael R Betts
Sep 3, 2020·Journal of Biological Rhythms·Shaon SenguptaGarret A FitzGerald
Aug 1, 2020·The Journal of Experimental Medicine·Tanya S FreedmanMatthew F Krummel
Oct 21, 2020·Journal of Intensive Care·Lorenzo GamberiniUNKNOWN ICU-RER COVID-19 Collaboration
Sep 26, 2020·The Journal of Clinical Investigation·Michael A Matthay, Katherine D Wick
Dec 3, 2020·Respiratory Research·Meghana RastogiSunit K Singh
Nov 13, 2020·Nature Communications·Shidan TosifNigel W Crawford
Dec 18, 2020·Journal of Intensive Care·Lorenzo GamberiniUNKNOWN ICU-RER COVID-19 Collaboration
Jun 19, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Mladen JergovićJanko Nikolich-Žugich
Nov 18, 2021·Clinical Microbiology Reviews·Fabián SalazarAdilia Warris

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Methods Mentioned

BETA
flow cytometry
PCA
FACS
FCS

Software Mentioned

FlowSOM
R function corrplot
R
xPONENT
GraphPad
hclust
R package rstatix
emdist
UMAP
Prism

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