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

• 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 Anantharajal Tambyah,
• Jenny Guek-Hong Low,
• Yee-Joo Tan &
• Antonio Bertoletti

Nature (2020)Cite this article

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Abstract

Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections¹. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

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Author notes

1. These authors contributed equally: Nina Le Bert, Anthony T. Tan

Affiliations

1. Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore
   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, Lin-Fa Wang, Eng Eong Ooi, Jenny Guek-Hong Low & Antonio Bertoletti
2. Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, Singapore
   Meiyin Lin & Yee-Joo Tan
3. National Center of Infectious Diseases, Singapore, Singapore
   Mark I-Cheng Chen
4. Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
   Shirin Kalimuddin & Jenny Guek-Hong Low
5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
   Paul Anantharajal Tambyah
6. Division of Infectious Disease, University Medicine Cluster, National University Hospital, Singapore, Singapore
   Paul Anantharajal Tambyah
7. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
   Yee-Joo Tan
8. Singapore Immunology Network, A*STAR, Singapore, Singapore
   Antonio Bertoletti

https://www.nature.com/articles/s41586-020-2550-z