Background:
There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative.
Methods:
Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients.
Findings:
We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses.
Interpretation:
Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID.
Author list:
Affiliations:
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
- Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
- Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
- Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK; Cambridge NIHR BioResource Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK; Department of Renal Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
- Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK; NHS Blood and Transplant, Cambridge CB2 0PT, UK.
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address: mrw1004@cam.ac.uk.
- Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK; Department of Infectious Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK. Electronic address: ns519@cam.ac.uk.
Authors:
Benjamin A Krishna 1, Eleanor Y Lim 2, Lenette Mactavous 3, NIHR BioResource Team; Paul A Lyons 1, Rainer Doffinger 4, John R Bradley 5, Kenneth G C Smith 1, John Sinclair 6, Nicholas J Matheson 7, Paul J Lehner 2, Mark R Wills 8, Nyaradzai Sithole 9
