Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19, 2025, Kwon et al

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

Ji-Soo Kwon, Euijin Chang, Hyeon Mu Jang, Ji Yeun Kim, Woori Kim, Ju Yeon Son, Junho Cha, Choi Young Jang, Seongman Bae, Jiwon Jung, Min Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Sung-Han Kim

Background/Aims
Post-acute sequelae of COVID-19 (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 cytokines 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.

Conclusions
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.

Link | PDF (Korean J Intern Med) [Open Access]
 
Editorial about this study:

Unraveling the immune responses in long COVID through cytokine profiling
Oh-Hyun Cho

[First paragraph with line breaks added]


As the unprecedented COVID-19 pandemic begins to subside, increasing attention has been directed toward the post-acute sequelae of SARS-CoV-2 infection (PASC) or long COVID, which affects a significant proportion of individuals recovering from the acute infection. PASC encompasses a wide range of physical, cognitive, and psychological symptoms that typically manifest within three months of the initial COVID-19 illness and persist for at least two months [1].

Extensive basic research has revealed three main mechanisms associated with PASC: persistence of the virus or its components in tissues; dysregulated immune responses, including T cell exhaustion, elevated cytokines, and autoimmunity; and endothelial inflammation with immune thrombosis [2]. However, a limited understanding of its natural history and pathogenesis continues to hinder a consensus on case definitions, making research in these areas particularly challenging.

The identification of pathogenesis-based biomarkers may significantly enhance the understanding and management of PASC. Kwon et al. provided additional insight into the immunopathogenesis of PASC [3]

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