Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients
Anthony T. Tan,
Martin Linster,
Chee Wah Tan,
Nina Le Bert,
Wan Ni Chia,
Kamini Kunasegaran,
Yan Zhuang,
Christine Y.L. Tham,
Adeline Chia,
Gavin J.D. Smith,
Barnaby Young,
Shirin Kalimuddin,
Jenny G.H. Low,
David Lye,
Lin-Fa Wang,
Antonio Bertoletti
Affiliations
Anthony T. Tan
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Martin Linster
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Chee Wah Tan
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Nina Le Bert
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Wan Ni Chia
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Kamini Kunasegaran
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Yan Zhuang
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Christine Y.L. Tham
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Adeline Chia
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Gavin J.D. Smith
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Barnaby Young
National Centre for Infectious Diseases, Singapore, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore; Lee Kong Cian School of Medicine, Singapore, Singapore
Shirin Kalimuddin
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
Jenny G.H. Low
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore; Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
David Lye
National Centre for Infectious Diseases, Singapore, Singapore; Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore; Lee Kong Cian School of Medicine, Singapore, Singapore; Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
Lin-Fa Wang
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
Antonio Bertoletti
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore; Singapore Immunology Network, A∗STAR, Singapore, Singapore; Corresponding author
Summary: Virus-specific humoral and cellular immunity act synergistically to protect the host from viral infection. We interrogate the dynamic changes of virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from disease onset to convalescence or death. We quantify SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells specific for various structural (nucleoprotein [NP], membrane [M], ORF3a, and spike) and non-structural (ORF7/8, NSP7, and NSP13) proteins. Although rapid induction and quantity of humoral responses associate with an increase in disease severity, early induction of interferon (IFN)-γ-secreting SARS-CoV-2-specific T cells is present in patients with mild disease and accelerated viral clearance. These findings provide support for the prognostic value of early functional SARS-CoV-2-specific T cells with important implications in vaccine design and immune monitoring.