SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls

Abstract

Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections 1. Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specific T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specific T cells in uninfected donors exhibited a different pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specific T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to 'common cold' human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specific and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N-and ORF1-specific T cells that are present in the general population affect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.

SARS-CoV-2 cellular immune response in uninfected health care workers with prolonged and close exposure to COVID-19 patients

“…In 39 uninfected HCWs largely exposed to COVID-19 patients, we demonstrated a consistent and polyfunctional production of cytokines in response to SARS-CoV-2 peptides, covering viral structural proteins S, M and N, that was similar to that observed in 17 convalescent HCWs, adjusted by age and sex. These ndings are in agreement with other works focused on SARS-CoV-2-speci c T cells that started to be characterized in COVID-19 patients and uninfected individuals [15][16][17][18][19][20] . Le Bert et al found speci c cellular responses in recovered patients and uninfected individuals mainly to structural protein (NP) and nonstructural proteins (NSP), although NPS response was rarely detected in SARS-COV-2 recovered individuals, measured by the production of IFN-γ and TNF-α by CD4 and CD8 T cells 17 .…”

Integrin activation enables simultaneous and sensitive detection of functional virus-specific CD4+ and CD8+ T cells

“…In line with other recent reports, we also observed in one unexposed donor very low frequencies of CD4 + and CD8 + T cells against spike and nucleocapsid proteins, respectively, probably due to cross-reactive cells primed against other SARS viruses [12][13][14]. We also used m24 Ab staining to con rm the induction of anti-vaccine CD4 + T cells after experimental immunization of a healthy volunteer with synthetic peptides from the spike and nucleocapsid proteins [9].…”

Identification and characterization of an immunodominant SARS-CoV-2-specific CD8 T cell response

“…However, much less is currently known regarding the SARS-CoV-2-speci c T cell response, in particular which parts of the virus are targeted by T cells. Both CD4 and CD8 T cells can recognize SARS-CoV-2 derived antigens 4,[6][7][8][9][10][11][12][13] . Most studies have focused on limited parts of the viral proteome 6,8,12 , and in particular the spike protein 4,10,13 , which was found to be a very important antigen source for virus speci c T cell responses in SARS-CoV-1 14 and MERS 15 .…”