Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19.

Jul 10, 2025The Korean journal of internal medicine

Immune signaling patterns linked to ongoing symptoms after COVID-19

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Abstract

In a study of 79 adults, fatigue was the most common symptom reported after COVID-19.

(PASC) symptoms vary widely among individuals.
Symptoms like fatigue, chronic cough, and brain fog were linked to increased levels of several , including IL-10 and inflammatory markers.
Certain symptoms, such as gastrointestinal issues and chest pain, were associated with significant increases in cytokine levels, indicating a possible shared pathophysiology.
Symptoms like chronic cough and dizziness did not show significant changes in cytokine levels.
The findings suggest that immune responses, including T-cell recruitment and increased vascular permeability, may play a role in different symptom clusters related to PASC.

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BACKGROUND/AIMS: (PASC) are highly heterogeneous; therefore, the pathophysiological mechanisms for PASC remain unclear. In this study, we aimed to examine the immunologic aspects of various PASC symptoms.

METHODS: We prospectively enrolled adults aged ≥ 18 years who were diagnosed with COVID-19 between August 2022 and September 2023. Blood samples were collected from all participants, who were interviewed using a questionnaire for PASC symptoms at least once between 1 and 6 months after the COVID-19 diagnosis. For immunological evaluation, plasma concentrations of SARS-CoV-2 spike subunit 1-specific IgG and 33 were measured using enzyme-linked immunosorbent assays and multiplex-based immunoassay, respectively.

RESULTS: In total, 156 pairs of blood samples and symptom reports from 79 participants were eligible for analysis. The most frequent symptom was fatigue, followed by post exertional malaise, chronic cough, thirst, and brain fog. Gastrointestinal symptoms, chest pain, post exertional malaise, smell/taste change, fatigue, brain fog, abnormal movement, and palpitation were accompanied by significant increases in IL-10, VEGF, and inflammatory cytokines like MIP-1α, IL-1β, IL-6, IL-8, MIG, granzyme A, and CX3CL1 levels, while chronic cough, dizziness, dyspnea, and hair loss were not accompanied by significant differences in cytokine levels.

CONCLUSION: Symptoms classified into different categories based on the dysfunctional organs may share a common pathophysiology regarding elevation of certain cytokines. Although PASC symptoms are heterogeneous, our findings suggest that T-cell recruitment, thrombosis, and increased vascular permeability might contribute to various symptom clusters sharing common pathophysiological mechanisms.

Key numbers

57.9 years

Mean age of participants

65.7%

Percentage of participants experiencing fatigue

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Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19.

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