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Distinguishing features of Long COVID identified through immune profiling

Klein, J; Wood, J; Jaycox, J; et. al., Nature

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Epub ahead of print indicates that the article has completed the peer review process and has been published online in advance of the actual print journal issue being released.
View epub on PubMed

Published

September 2023

Journal

Nature

Abstract

Post-acute infection syndromes (PAIS) may develop after acute viral disease. Infection with SARS-CoV-2 can result in the development of a PAIS known as "Long COVID" (LC). Individuals with LC frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the biological processes associated with the development and persistence of these symptoms are unclear. Here, 273 individuals with or without LC were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC. Marked differences were noted in circulating myeloid and lymphocyte populations relative to matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with LC. Further, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with LC, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with LC. Integration of immune phenotyping data into unbiased machine learning models identified key features most strongly associated with LC status. Collectively, these findings may help guide future studies into the pathobiology of LC and aid in developing relevant biomarkers.

Authors

Jon Klein, Jamie Wood, Jillian Jaycox, Rahul M Dhodapkar, Peiwen Lu, Jeff R Gehlhausen, Alexandra Tabachnikova, Kerrie Greene, Laura Tabacof, Amyn A Malik, Valter Silva Monteiro, Julio Silva, Kathy Kamath, Minlu Zhang, Abhilash Dhal, Isabel M Ott, Gabrielee Valle, Mario Peña-Hernandez, Tianyang Mao, Bornali Bhattacharjee, Takehiro Takahashi, Carolina Lucas, Eric Song, Dayna Mccarthy, Erica Breyman, Jenna Tosto-Mancuso, Yile Dai, Emily Perotti, Koray Akduman, Tiffany J Tzeng, Lan Xu, Anna C Geraghty, Michelle Monje, Inci Yildirim, John Shon, Ruslan Medzhitov, Denyse Lutchmansingh, Jennifer D Possick, Naftali Kaminski, Saad B Omer, Harlan M Krumholz, Leying Guan, Charles S Dela Cruz, David van Dijk, Aaron M Ring, David Putrino, Akiko Iwasaki

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