Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome

Daniela Weiskopf1, Katharina S Schmitz2, Matthijs P Raadsen2, Alba Grifoni1, Nisreen M A Okba2, Henrik Endeman3, Johannes P C van den Akker3, Richard Molenkamp2, Marion P G Koopmans2, Eric C M van Gorp2, Bart L Haagmans2, Rik L de Swart2, Alessandro Sette1,4,5, Rory D de Vries6

  1. Center for Infectious Disease, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  2. Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
  3. Department of Intensive Care, Erasmus MC, Rotterdam, the Netherlands.
  4. Department of Pathology, University of California, San Diego, CA 92037, USA.
  5. Department of Medicine, University of California, San Diego, CA 92037, USA.
  6. Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands. r.d.devries@erasmusmc.nl.

Abstract

SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients the infection results in moderate to severe acute respiratory distress syndrome (ARDS), requiring invasive mechanical ventilation. High serum levels of IL-6, IL-10 and an immune hyperresponsiveness referred to as a 'cytokine storm' have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2-specific T cells is limited. Here, we studied 10 COVID-19 patients who required admission to an intensive care unit and detected SARS-CoV-2-specific CD4+ and CD8+ T cells in 10 out of 10 and 8 out of 10 patients, respectively. We also detected low levels of SARS-CoV-2-reactive T cells in 2 out of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with 'common cold' coronaviruses. The strongest T-cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2-specific T cells predominantly produced effector and Th1 cytokines, although Th2 and Th17 cytokines were also detected. Furthermore, we studied T-cell kinetics and showed that SARS-CoV-2-specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T-cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation.

Presented By Katharina Schmitz

Immunology & Microbiology, Medicine, COVID-19Nicholas Liao2020-06