T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID.

T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID.

Publication date: Nov 08, 2023

As about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID. To this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later. None of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36. 9 +/- 14. 7 vs. 24. 2 +/- 9. 0%, p = 0. 016). Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.

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Concepts Keywords
Covid Apoptosis
Lymphopenia COVID-19
Th17 Cytokines
Viruses Cytokines
Disease Progression
helper T lymphocyte
immune activation
Leukocytes, Mononuclear
Post-Acute COVID-19 Syndrome
post-acute COVID-19 syndrome
programmed cell death
SARS-CoV-2 infection sequelae


Type Source Name
pathway KEGG Apoptosis
disease MESH SARS-CoV-2 infection
disease MESH long COVID
disease MESH sequelae
drug DRUGBANK Tropicamide
disease IDO blood
disease MESH lymphopenia
disease VO Viruses
disease MESH autoimmunity
disease MESH Emergency
disease MESH death
disease IDO acute infection
disease MESH neurocognitive disorders
disease MESH insomnia
disease VO organization
disease MESH inflammation
disease VO frequency
pathway KEGG Necroptosis
disease VO efficient
drug DRUGBANK L-Isoleucine
drug DRUGBANK Edetic Acid
disease MESH Infectious Diseases
drug DRUGBANK Oxygen
drug DRUGBANK Medical air
disease MESH infection
disease MESH neurologic disorders
disease MESH syndrome
drug DRUGBANK Aspartame
pathway KEGG Platelet activation
disease MESH Disease Progression

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