Distinguishing features of long COVID identified through immune profiling

Post-acute infection syndromes can follow viral illnesses. SARS-CoV-2 infection may lead to long COVID, characterized by fatigue, post-exertional malaise, and cognitive/autonomic dysfunctions. The biological processes driving these symptoms are unclear. In a cross-sectional study of 275 individuals with or without long COVID, multidimensional immune phenotyping and unbiased machine learning identified biological features associated with long COVID. Participants with long COVID showed marked differences in circulating myeloid and lymphocyte populations and exaggerated humoral responses to SARS-CoV-2. Elevated antibody responses to non-SARS-CoV-2 viruses, particularly Epstein–Barr virus, were observed. Levels of soluble immune mediators and hormones varied, with lower cortisol among long COVID participants. Integration of immune data into machine learning models identified key features most strongly associated with long COVID status, providing direction for future pathobiology studies and biomarker development.

Jon Klein, Jamie Wood, Jillian R. 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-Hernández, 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