Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence

TLDR

SARS‑CoV‑2 has infected over 200 million people and caused more than 4 million deaths, yet most (>80 %) experience mild disease and recover at home, a setting that has received comparatively little immune‑profiling attention. The study aimed to identify and validate a persistent inflammatory signature in individuals with post‑acute sequelae of SARS‑CoV‑2 infection (PASC) by characterizing recovery‑associated signals. The authors performed deep longitudinal immune profiling of mild COVID‑19 patients from 1–15 days post‑infection to over 100 days, integrating single‑cell blood analyses, serum proteomics, virus‑specific cellular and humoral responses, and clinical metadata. Acute infection triggered vigorous innate and adaptive activation that varied with age, and a persistent inflammatory cytokine, gene expression, and chromatin accessibility signature was identified in patients with PASC.

Abstract

SARS-CoV-2 has infected over 200 million and caused more than 4 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID-19 beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive immune activation that differed in character by age (young vs. old). We then characterized signals associated with recovery and convalescence to define and validate a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).