Detection of pre-existing SARS-CoV-2-reactive T cells in unexposed renal transplant patients

Moritz Anft,Richard Viebahn,Mira Choi,Eike Steinmann,Nina Babel,Ulrik Stervbo,Sarah Skrzypczyk,Christian Hugo,Petra Reinke,Oliver Witzke,Arturo Blazquez-Navarro,Toni Luise Meister,Peter Schenker,Rainer Wirth,Stephanie Pfaender,Timm H Westhoff

doi:10.1007/s40620-021-01092-0

Abstract

BackgroundRecent data demonstrate potentially protective pre-existing T cells reactive against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in samples of healthy blood donors, collected before the SARS-CoV-2 pandemic. Whether pre-existing immunity is also detectable in immunosuppressed patients is currently not known.MethodsFifty-seven patients were included in this case–control study. We compared the frequency of SARS-CoV-2-reactive T cells in the samples of 20 renal transplant (RTx) patients to 20 age/gender matched non-immunosuppressed/immune competent healthy individuals collected before the onset of the SARS-CoV-2 pandemic. Seventeen coronavirus disease 2019 (COVID-19) patients were used as positive controls. T cell reactivity against Spike-, Nucleocapsid-, and Membrane- SARS-CoV-2 proteins were analyzed by multi-parameter flow cytometry. Antibodies were analyzed by neutralization assay.ResultsPre-existing SARS-CoV-2-reactive T cells were detected in the majority of unexposed patients and healthy individuals. In RTx patients, 13/20 showed CD4+ T cells reactive against at least one SARS-CoV-2 protein. CD8+ T cells reactive against at least one SARS-CoV-2 protein were demonstrated in 12/20 of RTx patients. The frequency and Th1 cytokine expression pattern of pre-formed SARS-CoV-2 reactive T cells did not differ between RTx and non-immunosuppressed healthy individuals.ConclusionsThis study shows that the magnitude and functionality of pre-existing SARS-CoV-2 reactive T cell in transplant patients is non-inferior compared to the immune competent cohort. Although several pro-inflammatory cytokines were produced by the detected T cells, further studies are required to prove their antiviral protection.Graphic abstract

Highlights

The 2020 pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in over thirty million confirmed cases of coronavirus disease 2019 (COVID-19) and over two million associated deaths by January 2021 [1]
By analyzing SARS-CoV-2 reactive CD4+ T memory cell subsets, we found that RTx patients and healthy individuals did not differ with regard to the frequency of effector memory, central memory or T effector memory RA (TEMRA) cells
The lack of antiviral therapies makes it indispensable to identify risk groups in order to protect them from infections, which otherwise could result in a severe COVID-19 course

Summary

Introduction

The 2020 pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in over thirty million confirmed cases of coronavirus disease 2019 (COVID-19) and over two million associated deaths by January 2021 [1]. While investigating blood samples collected before the pandemic, it became clear that healthy individuals with no prior contact with the virus harbor SARS-CoV-2 reactive T cells [6, 7, 15, 16] These T cells probably arise due to infections with endemic coronaviruses which have recently been associated with less severe COVID-19 [17]. Recent data demonstrate potentially protective pre-existing T cells reactive against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in samples of healthy blood donors, collected before the SARS-CoV-2 pandemic. We compared the frequency of SARS-CoV-2-reactive T cells in the samples of 20 renal transplant (RTx) patients to 20 age/gender matched non-immunosuppressed/immune competent healthy individuals collected before the onset of the SARS-CoV-2 pandemic. Several pro-inflammatory cytokines were produced by the detected T cells, further studies are required to prove their antiviral protection

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