Immunological and clinical markers of PASC: Insights from mild and severe cases six months post-infection, 2025, William Mouton et al

Abstract
Post-acute sequelae of COVID-19 (PASC) is a complex and multifaceted clinical challenge requiring to emphasize its underlying pathophysiological mechanisms.

This study assessed hundreds of virological, serological, immunological, and tissue damage biomarkers in two patient cohorts who experienced 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 mains 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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(Supplementary figures not currently downloadable)

 

Completely anecdotal, but I have severe PASC (ME/CFS) and I don’t have EBV antibodies.

 

I also have CMV IgG, but not IgM.

 

So IgG,IgM (EBNA, VCA etc) are all negative, or you've had a past infection but no indication of anything more recent (as in most people with ME/CFS)?

 

Yes. I got ME/CFS from PCR-confirmed Covid three years ago.

• Negative EBV EBNA (IgG and IgM) and VCA (IgG)
• Negative Paravirus B19 IgG and IgM
• Positive CMV IgG, negative IgM
• Positive Varicella-zoster virus IgG

 

I have no idea how I got it. Idk if my sisters had it. One had mono as a child, all three of us had Varielle Zoster (vannkopper/chicken pox) before school age.