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

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-g 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. Copyright Crown Copyright (C) 2022 Published by Elsevier B.V.

Automated summary

There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. Given the diagnostic challenges of Long COVID, this study investigated SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID. The findings suggest that IL-2 release from T cells may be a sensitive and specific marker for previous SARS-CoV-2 infection, even in patients without detectable SARS-CoV-2 antibodies.