Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID-Reference-Cited by-同舟云学术

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

Published:2022-09-13 Issue: Volume: Page:
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Author:

Krishna Benjamin A.¹,Lim Eleanor Y.¹,Mactavous Lenette²,Jackson Sarah¹^ORCID,Team NIHR BioResource¹,Lyons Paul A.³^ORCID,Doffinger Rainer¹,Bradley John R.¹^ORCID,Smith Kenneth G. C.¹,Sinclair John⁴,Matheson Nicholas J.¹^ORCID,Lehner Paul J.¹^ORCID,Sithole Nyaradzai¹^ORCID,Wills Mark R.¹

Affiliation:

1. University of Cambridge

2. Cambridge University Hospitals NHS Foundation Trust

3. Cambridge Institute for Medical Research

4. Cambridge University

Abstract

Abstract After acute infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), a significant proportion (0.2–30%) of patients experience persistent symptoms beyond 12 weeks, termed Long COVID. Understanding the mechanisms which cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic and monitoring purposes is urgently required. Persistently high levels of IFN-γ were detected from peripheral blood mononuclear cells (PBMCs) of Long COVID patients using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in Long Covid patients, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. IFN-γ release was CD8+ T cell mediated and dependent on MHC-I antigen presentation by CD14+ cells. After vaccination, a significant decrease in IFN-γ correlated with resolution of some Long COVID symptoms. Our study highlights a key mechanism underlying Long COVID, enabling the search for biomarkers and therapeutics in patients with Long COVID.

Publisher

Research Square Platform LLC

Reference42 articles.

1. Scherlinger, M., et al., Refining “Long-COVID” by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection. Infectious Diseases and Therapy, 2021: p. 1–17.

2. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study;Huang C;The Lancet,2021

3. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study;Ayoubkhani D;bmj,2021

4. Extrapulmonary manifestations of COVID-19.;Gupta A;Nature medicine,2020

5. Thompson, E.J., et al., Risk factors for long COVID: analyses of 10 longitudinal studies and electronic health records in the UK. medRxiv, 2021.