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.
Highlights
A novel coronavirus named SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease, referred to as COVID-19 [1, 2]
We provide evidence that SARS-CoV-2-specific CD4+ and CD8+ T cells appear in blood of acute respiratory distress syndrome (ARDS) patients in the first two weeks post immunology.sciencemag.org (Page numbers not final at time of first release) 3 onset of symptoms
It is important to mention that this study focused on peripheral blood mononuclear cells (PBMC) samples, but tissue-resident T cells undoubtedly play an important role in this early response
Summary
A novel coronavirus named SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease, referred to as COVID-19 [1, 2]. A transient increase in co-expression of CD38 and HLA-DR by T cells, a phenotype of CD8+ T-cell activation in response to viral infection, was observed concomitantly [5]. This increase in both CD4+ and CD8+ CD38+HLA-DR+ T cells preceded resolution of clinical symptoms in a non-severe, recovered, COVID-19 patient [6]. Grifoni et al reported the presence of SARS-CoV-2-specific T cells in convalescent samples from predominantly mild COVID-19 patients. They showed strong reactivity to the viral S and M proteins, and strong CD4+ T-cell responses to N. Virus-specific T cells have been detected after exposure to the related SARS-CoV and MERS-CoV,
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