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Evidence of previous SARS-CoV-2 infection in seronegative patients with long COVID.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Krishna, Benjamin Anthony Cates  ORCID logo  https://orcid.org/0000-0003-0919-2961
Lim, Eleanor Y 
Mactavous, Lenette 
NIHR BioResource Team 
Lyons, Paul A 

Abstract

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. FUNDING: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).

Description

Keywords

Assay, Immunity, Long COVID, SARS-CoV-2, T cell, Antibodies, Viral, COVID-19, Humans, Interleukin-2, SARS-CoV-2, Post-Acute COVID-19 Syndrome

Journal Title

EBioMedicine

Conference Name

Journal ISSN

2352-3964
2352-3964

Volume Title

81

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (084957/Z/08/Z)
Wellcome Trust (210688/Z/18/Z)
MRC (MR/V011561/1)
MRC (via University of Birmingham) (MR/V028448/1)
Department of Health (via National Institute for Health Research (NIHR)) (COV-LT2-0004)
Addenbrooke's Charitable Trust (ACT) (900276)
MRC (MR/T032413/1)
Medical Research Council (MR/S00081X/1)