Journal of medical virologyDec 2, 2022

Blood markers of immune cell imbalance and virus protein show biological differences in long COVID patients

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Feb 20, 2026

Abstract

At a median time of 8 months after infection, pronounced dysregulation in almost all tested soluble factors was observed in 181 individuals affected by COVID-19.

Dysregulation included both pro-inflammatory and pro-fibrotic cytokines, indicating significant immune system alterations.
Immunological perturbations were largely independent of ongoing symptoms.
PASC-specific patterns were suggested involving CCL2/MCP-1 and IL-8, correlating with several other immune factors.
Circulating SARS-CoV-2 spike (S1) protein levels did not correlate with any of the analyzed immune factors.
Findings confirm immune dysregulation and persistent viral proteins in individuals with PASC, highlighting biological heterogeneity.

Simplified

Post-acute sequelae of COVID-19 () are long-term consequences of SARS-CoV-2 infection that can substantially impair the quality of life. Underlying mechanisms ranging from persistent viruses to innate and adaptive immune dysregulation have been discussed. Here, we profiled the plasma of 181 individuals from the cohort study for digital health research in Germany (DigiHero), including individuals after mild to moderate COVID-19 with or without PASC and uninfected controls. We focused on soluble factors related to monocyte/macrophage biology and on circulating SARS-CoV-2 spike (S1) protein as a potential biomarker for persistent viral reservoirs. At a median time of 8 months after infection, we found pronounced dysregulation in almost all tested soluble factors, including both pro-inflammatory and pro-fibrotic cytokines. These immunological perturbations were remarkably independent of ongoing PASC symptoms per se, but further correlation and regression analyses suggested PASC-specific patterns involving CCL2/MCP-1 and IL-8 that either correlated with sCD162, sCD206/MMR, IFN-α2, IL-17A and IL-33, or IL-18 and IL-23. None of the analyzed factors correlated with the detectability or levels of circulating S1, indicating that this represents an independent subset of patients with PASC. These data confirm prior evidence of immune dysregulation and persistence of viral protein in PASC and illustrate its biological heterogeneity that still awaits correlation with clinically defined PASC subtypes.

Key numbers

91 of 181

Increased Cytokine Levels

Individuals with ongoing out of total participants analyzed.

64%

Circulating S1 Detection

Percentage of individuals with ongoing showing detectable levels of circulating S1 protein.

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Blood markers of immune cell imbalance and virus protein show biological differences in long COVID patients

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