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

Nina Le Bert, Anthony T. Tan, Kamini Kunasegaran, Christine Y. L. Tham, Morteza Hafezi, Adeline Chia, Melissa Hui Yen Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajah Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan and Antonio Bertoletti ()
Additional contact information
Nina Le Bert: Duke-NUS Medical School
Anthony T. Tan: Duke-NUS Medical School
Kamini Kunasegaran: Duke-NUS Medical School
Christine Y. L. Tham: Duke-NUS Medical School
Morteza Hafezi: Duke-NUS Medical School
Adeline Chia: Duke-NUS Medical School
Melissa Hui Yen Chng: Duke-NUS Medical School
Meiyin Lin: Duke-NUS Medical School
Nicole Tan: Duke-NUS Medical School
Martin Linster: Duke-NUS Medical School
Wan Ni Chia: Duke-NUS Medical School
Mark I-Cheng Chen: National Centre of Infectious Diseases
Lin-Fa Wang: Duke-NUS Medical School
Eng Eong Ooi: Duke-NUS Medical School
Shirin Kalimuddin: Singapore General Hospital
Paul Anantharajah Tambyah: Yong Loo Lin School of Medicine, National University of Singapore
Jenny Guek-Hong Low: Duke-NUS Medical School
Yee-Joo Tan: Institute of Molecular and Cell Biology (IMCB), A*STAR
Antonio Bertoletti: Duke-NUS Medical School

Nature, 2020, vol. 584, issue 7821, 457-462

Abstract: Abstract Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections1. 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.

Date: 2020
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DOI: 10.1038/s41586-020-2550-z

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