Distinguishing features of long COVID identified through immune profiling
Author:
Klein JonORCID, Wood Jamie, Jaycox Jillian R., Dhodapkar Rahul M.ORCID, Lu PeiwenORCID, Gehlhausen Jeff R., Tabachnikova Alexandra, Greene Kerrie, Tabacof Laura, Malik Amyn A., Silva Monteiro ValterORCID, Silva JulioORCID, Kamath Kathy, Zhang MinluORCID, Dhal Abhilash, Ott Isabel M., Valle Gabrielee, Peña-Hernández Mario, Mao TianyangORCID, Bhattacharjee BornaliORCID, Takahashi TakehiroORCID, Lucas CarolinaORCID, Song EricORCID, McCarthy Dayna, Breyman Erica, Tosto-Mancuso Jenna, Dai YileORCID, Perotti Emily, Akduman Koray, Tzeng Tiffany J., Xu Lan, Geraghty Anna C., Monje MichelleORCID, Yildirim InciORCID, Shon John, Medzhitov RuslanORCID, Lutchmansingh Denyse, Possick Jennifer D., Kaminski NaftaliORCID, Omer Saad B.ORCID, Krumholz Harlan M.ORCID, Guan Leying, Dela Cruz Charles S.ORCID, van Dijk DavidORCID, Ring Aaron M.ORCID, Putrino DavidORCID, Iwasaki AkikoORCID
Abstract
AbstractPost-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2–4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein–Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference81 articles.
1. Choutka, J., Jansari, V., Hornig, M. & Iwasaki, A. Unexplained post-acute infection syndromes. Nat. Med. 28, 911–923 (2022). 2. Thaweethai, T. et al. Development of a definition of postacute sequelae of SARS-CoV-2 Infection. JAMA 329, 1934–1946 (2023). 3. Nalbandian, A. et al. Post-acute COVID-19 syndrome. Nat. Med. 27, 601–615 (2021). 4. Michelen, M. et al. Characterising long COVID: a living systematic review. BMJ Glob. Health 6, e005427 (2021). 5. Wiedemann, A. et al. Long-lasting severe immune dysfunction in Ebola virus disease survivors. Nat. Commun. 11, 3730 (2020).
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