Post-Acute COVID Biomarker Patterns Vary by Symptom and Time

In patients with post-acute sequelae of SARS-CoV-2 infection (PASC), biomarker profiles varied according to symptom type and time since infection, and levels of inflammatory biomarkers (IFN gamma and CD163) and vascular activation biomarkers (VCAM-1 and ICAM-1) showed strong correlations with specific long-COVID symptoms.
METHODOLOGY:
PASC affects a considerable number of people after mild acute SARS-CoV-2 infection, but data on its pathophysiologic mechanisms remain limited. In this study, researchers explored symptoms associated with PASC and examined its association with a range of blood biomarkers.
They included participants with prior SARS-CoV-2 infection either asymptomatic or without persistent symptoms categorized into recovered (n = 490) and PASC (n = 311) groups, using data from three French population-based cohorts collected between February 2020 and October 2021.
Participants received two home visits at baseline and 6 months for biological sample collection and completed questionnaires covering medical history, infection status, vaccination status, symptoms, and mental health.
Researchers assessed 14 blood biomarkers, including cytokines, chemokines, immune checkpoints, cell adhesion molecules, and markers of macrophage activation and vascular damage, which are known to be involved in the pathophysiologic mechanisms of SARS-CoV-2 infection.
TAKEAWAY:
Participants with PASC commonly reported persistent fatigue, breathlessness, cough, and sleep disorders, along with higher rates of depression and anxiety.
Inflammatory biomarkers linked to COVID-19 severity (IFN gamma and CD163) and vascular activation markers (VCAM-1 and ICAM-1) showed significant correlations with specific PASC symptoms, particularly among participants infected within the past year; however, these associations largely disappeared over time.
Viral activation markers (PD-L1 and IP-10) were positively associated with acute-phase symptoms such as anosmia/ageusia and cough, particularly in recent infections.
Complete symptom resolution was more common among participants with recent infections (< 1 year ago) than among those infected a year ago, occurring in 38% vs 20% of cases ( P = .04). Overall, 74% of individuals experienced a resolution of at least one symptom.
IN PRACTICE:
'Biomarker profiles appear to vary according to symptom type and the time elapsed since infection. Consequently, research efforts and treatment strategies should take these parameters into account,' the authors wrote.
SOURCE:
This study was led by Olivier Robineau, Sorbonne Université, Inserm, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Paris, France. It was published online on May 30, 2025, in eBioMedicine .
LIMITATIONS:
Individuals with more severe symptoms may have been particularly motivated to participate, introducing selection bias. Additionally, as most biomarker measurements were taken long after participants' initial infection and only a few participants had recent infections, the ability to identify associations specific to the acute phase was likely diminished.
DISCLOSURES:
This study received funding from the French Ministry of Health and Prevention and the French Ministry of Higher Education, Research and Innovation. Two authors disclosed receiving financial support from Gilead, ViiV, MSD, Moderna, or Pfizer or nonfinancial support from Nordic Pharma France.

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