Redefining Normal: Cytokine Dysregulation in Long COVID and the Post-Pandemic Healthy Donors.

Redefining Normal: Cytokine Dysregulation in Long COVID and the Post-Pandemic Healthy Donors.

Publication date: Aug 29, 2025

The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance-particularly in cytokine networks-our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes.

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Concepts Keywords
Healthy COVID-19
Mortality cytokines
Orchestrators healthy donors
Pdgf long COVID
Remodeling pandemic
recovered individuals

Semantics

Type Source Name
disease MESH Long COVID
disease MESH COVID-19 pandemic
pathway REACTOME SARS-CoV-2 Infection
drug DRUGBANK Binetrakin
drug DRUGBANK BK-MDA
drug DRUGBANK Vanillic acid
drug DRUGBANK Basic Fibroblast Growth Factor
disease MESH cognitive dysfunction
disease MESH brain fog
disease MESH dyspnea
disease MESH infection
pathway REACTOME Immune System
disease IDO cell
disease MESH lymphopenia
disease MESH cytokine storm
disease IDO susceptibility
disease MESH reinfection
disease MESH autoimmunity
disease IDO process
disease MESH inflammation
disease MESH neuroinflammation
disease MESH hypertension
disease MESH hair loss
drug DRUGBANK Filgrastim
disease IDO immune response
disease IDO acute infection
disease IDO blood
disease MESH fibrosis
disease MESH aplastic anemia
disease MESH neutropenia
drug DRUGBANK Hyaluronic acid
disease MESH respiratory failure
disease MESH pathological processes
disease IDO production
disease MESH thromboinflammation
disease MESH lung injury
disease MESH dysautonomia
disease MESH paresthesias
disease MESH chest pain
disease MESH orthostatic intolerance
disease MESH influenza
disease MESH secondary infection
disease MESH T cell exhaustion
disease MESH viral infections
disease IDO pathogen
disease MESH convalescence
disease IDO history
disease MESH anxiety
disease MESH depression
drug DRUGBANK Edetic Acid
disease MESH privacy
pathway REACTOME Translation
disease MESH Syndrome
disease IDO host
disease MESH Chronic Fatigue Syndrome
disease MESH Cancer
disease MESH Allergy
disease MESH Abnormalities
disease MESH Breakthrough Infection
pathway REACTOME Metabolism
drug DRUGBANK Isoxaflutole
drug DRUGBANK Methylergometrine
disease MESH Chronic Illnesses

Original Article

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