Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Abstract The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characte...

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Published inbioRxiv
Main Authors Nina Le Bert, Clapham, Hannah E, Tan, Anthony T, Wan Ni Chia, Christine Yl Tham, Lim, Jane M, Kunasegaran, Kamini, Tan, Linda, Charles-Antoine Dutertre, Shankar, Nivedita, Lim, Joey Me, Louisa Jin Sun, Zahari, Marina, Tun, Zaw Myo, Kumar, Vishakha, Beng Lee Lim, Lim, Siew Hoon, Chia, Adeline, Yee-Joo, Tan, Tambyah, Paul Anantharajah, Kalimuddin, Shirin, Lye, David, Low, Jenny Gh, Lin-Fa, Wang, Wan, Wei Yee, Li Yang Hsu, Bertoletti, Antonio, Tam, Clarence C
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LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.11.2020
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Abstract Abstract The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance. Competing Interest Statement The authors have declared no competing interest. Footnotes * One Sentence Summary: Virus-specific T cells secrete high levels of IFN-γ and IL-2 in asymptomatic SARS-CoV-2 infection.
AbstractList Abstract The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance. Competing Interest Statement The authors have declared no competing interest. Footnotes * One Sentence Summary: Virus-specific T cells secrete high levels of IFN-γ and IL-2 in asymptomatic SARS-CoV-2 infection.
Author Tan, Anthony T
Tun, Zaw Myo
Li Yang Hsu
Kalimuddin, Shirin
Lim, Joey Me
Tan, Linda
Christine Yl Tham
Kunasegaran, Kamini
Lim, Siew Hoon
Low, Jenny Gh
Chia, Adeline
Tambyah, Paul Anantharajah
Lye, David
Nina Le Bert
Kumar, Vishakha
Wan Ni Chia
Zahari, Marina
Tam, Clarence C
Shankar, Nivedita
Lim, Jane M
Charles-Antoine Dutertre
Louisa Jin Sun
Beng Lee Lim
Wan, Wei Yee
Bertoletti, Antonio
Clapham, Hannah E
Yee-Joo, Tan
Lin-Fa, Wang
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Snippet Abstract The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features....
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SubjectTerms Asymptomatic
Asymptomatic infection
Cell activation
COVID-19
Cytokines
Enzyme-linked immunosorbent assay
IL-1β
Immune clearance
Immune response (cell-mediated)
Infections
Inflammation
Interleukin 10
Interleukin 2
Interleukin 4
Interleukin 6
Lymphocytes
Lymphocytes T
Seroconversion
Severe acute respiratory syndrome coronavirus 2
Structural proteins
Tumor necrosis factor-α
Viruses
γ-Interferon
Title Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
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