A methylation clock model of mild SARS‐CoV‐2 infection provides insight into immune dysregulation
Abstract
DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 15, 2023
- Source ID
- 10.15252/msb.202211361
Entities
People
- Alessandra Soares‐schanoski
- Andrew G. Letizia
- Antonio Cappuccio
- Biobank Team
- Carl W. Goforth
- Clare M. Miller
- Dawn L. Weir
- Elena Zaslavsky
- German Nudelman
- Hanna Pincas
- Irene Ramos
- Kristy Guevara
- Maria Chikina
- Mary Anne S. Amper
- Mary‐catherine George
- Miriam Merad
- Mital Vasoya
- Nada Marjanovic
- Olga G. Troyanskaya
- Rachel S G Sealfon
- Sacha Gnjatic
- Seunghee Kim‐schulze
- Sindhu Vangeti
- Stuart C. Sealfon
- Venugopalan Nair
- Weiguang Mao
- Yongchao Ge
Organizations
- Defense Advanced Research Projects Agency
- Defense Health Agency
- Flatiron Institute
- Icahn School of Medicine at Mount Sinai
- National Institutes of Health
- Naval Medical Research Center
- Princeton University
- University of Pittsburgh