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Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.

Accepted version
Peer-reviewed

Type

Article

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Abstract

After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.

Description

Keywords

Humans, Biomarkers, CD8-Positive T-Lymphocytes, COVID-19, Interferon-gamma, Leukocytes, Mononuclear, Post-Acute COVID-19 Syndrome, SARS-CoV-2

Journal Title

Sci Adv

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

Publisher

American Association for the Advancement of Science (AAAS)
Sponsorship
Wellcome Trust (225023/Z/22/Z)
Wellcome Trust (084957/Z/08/Z)
Wellcome Trust (200871/Z/16/Z)
Wellcome Trust (210688/Z/18/Z)
MRC (MR/V011561/1)
MRC (MR/T032413/1)
Medical Research Council (MR/W018861/1)