Reactive T Cells in Convalescent COVID-19 Patients With Negative SARS-CoV-2 Antibody Serology.

Sophie Steiner,Victor M Corman,Leif G Hanitsch,Christian Drosten,Sandra Bauer,Franziska Sotzny,Tatjana Schwarz,Carmen Scheibenbogen,Hans-Dieter Volk

doi:10.3389/fimmu.2021.687449

Abstract

Despite RT-PCR confirmed COVID-19, specific antibodies to SARS-CoV-2 spike are undetectable in serum in approximately 10% of convalescent patients after mild disease course. This raises the question of induction and persistence of SARS-CoV-2-reactive T cells in these convalescent individuals. Using flow cytometry, we assessed specific SARS-CoV-2 and human endemic coronaviruses (HCoV-229E, -OC43) reactive T cells after stimulation with spike and nucleocapsid peptide pools and analyzed cytokine polyfunctionality (IFNγ, TNFα, and IL-2) in seropositive and seronegative convalescent COVID-19 patients as well as in unexposed healthy controls. Stimulation with SARS-CoV-2 spike and nucleocapsid (NCAP) as well as HCoV spike peptide pools elicited a similar T cell response in seropositive and seronegative post COVID-19 patients. Significantly higher frequencies of polyfunctional cytokine nucleocapsid reactive CD4+ T cells (triple positive for IFNγ, TNFα, and IL-2) were observed in both, seropositive (p = 0.008) and seronegative (p = 0.04), COVID-19 convalescent compared to healthy controls and were detectable up to day 162 post RT-PCR positivity in seronegative convalescents. Our data indicate an important role of NCAP-specific T cells for viral control.

Highlights

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
In mild COVID-19, specific IgG antibodies to SARS-CoV-2 are undetectable in approximately 10% of convalescent individuals [9, 10]
There are reports on patients with immune deficiencies that suffer only mild COVID-19 disease despite their inability to mount specific antibodies against SARS-CoV-2 [17,18,19,20,21,22,23,24] In this study, we provide evidence that SARS-CoV-2-reactive T cells to S and nucleocapsid protein (NCAP) of SARS-CoV-2 can be identified by dp spike and tp NCAP profiles in seronegative patients with mild COVID-19

Summary

Introduction

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In response to an infection with SARSCoV-2, mechanisms of cellular and humoral immunity have been described [1,2,3,4,5,6]. To date, it remains uncertain whether convalescent SARS-CoV-2 infected patients develop a robust and long. Persistence of specific IgG antibodies to SARSCoV-2 in serum correlates with clinical severity during acute infection and antibodies were found to decline more rapidly in asymptomatic patients [9]. While high neutralizing antibody titer are only found in the minority of convalescent patients [7, 10], they were shown to correlate with numbers of virus-specific T cells [8, 11]. In convalescent patients, polyfunctional SARS-CoV-2-specific T cells have been described, indicating the generation of a memory-like phenotype [6, 12, 13]

Methods

Results

Conclusion