Immunological and Clinical Markers of Post-acute Sequelae of COVID-19: Insights from Mild and Severe Cases 6 Months Post-infection.

Publication date: Jul 01, 2025

Post-acute sequelae of COVID-19 (PASC) are a complex clinical condition that requires a better understanding of its underlying biological mechanisms. In this study, we assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two cohorts of patients who had experienced either mild (n = 270) or severe (n = 188) COVID-19, 6 to 9 months post-initial infection, and in which 40% and 57. 4% of patients, respectively, developed PASC. Blood analysis showed that the main differences observed in humoral, viral, and biological biomarkers were associated with the initial COVID-19 severity, rather than being specifically linked to PASC. However, patients with PASC displayed altered CD4 and CD8 memory T cell subsets, with higher cytokine-secreting cells and increased terminally differentiated CD45RA effector memory T cells (TEMRA). Elevated SARS-CoV-2-specific T cells responsive to nucleocapsid/membrane proteins with a TEMRA phenotype were also observed. A random forest model identified these features and initial symptom duration as top variables discriminating PASC, achieving over 80% classification accuracy.

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Concepts Keywords
Cd4 Adult
Immunological Aged
Months biological biomarkers
Severe Biomarkers
Viral Biomarkers
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
COVID-19
Cytokines
Cytokines
Female
Humans
humoral
Immunologic Memory
Male
Memory T Cells
Middle Aged
Post-Acute COVID-19 Syndrome
SARS-CoV-2
SARS‐CoV‐2
T cell phenotyping
virological

Semantics

Type Source Name
disease MESH Post-acute Sequelae of COVID-19
disease MESH infection
drug DRUGBANK Tropicamide
disease MESH COVID-19
disease IDO blood
disease IDO cell
disease IDO symptom
disease MESH Sequelae
drug DRUGBANK Tretamine
drug DRUGBANK Serine
drug DRUGBANK Dimercaprol
disease MESH dyspnea
disease MESH cognitive impairments
disease MESH anosmia
disease MESH ageusia
disease MESH inflammation
disease MESH heart failure

Original Article

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