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

• Published in: bioRxiv
• 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
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.11.2020
• Subjects: 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
• DOI: 10.1101/2020.11.25.399139

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.