PT - JOURNAL ARTICLE AU - Bert, Nina Le AU - Clapham, Hannah E AU - Tan, Anthony T AU - Chia, Wan Ni AU - Tham, Christine YL AU - Lim, Jane M AU - Kunasegaran, Kamini AU - Tan, Linda AU - Dutertre, Charles-Antoine AU - Shankar, Nivedita AU - Lim, Joey ME AU - Sun, Louisa Jin AU - Zahari, Marina AU - Tun, Zaw Myo AU - Kumar, Vishakha AU - Lim, Beng Lee AU - Lim, Siew Hoon AU - Chia, Adeline AU - Tan, Yee-Joo AU - Tambyah, Paul Anantharajah AU - Kalimuddin, Shirin AU - Lye, David AU - Low, Jenny GH AU - Wang, Lin-Fa AU - Wan, Wei Yee AU - Hsu, Li Yang AU - Bertoletti, Antonio AU - Tam, Clarence C TI - Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection AID - 10.1101/2020.11.25.399139 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.25.399139 4099 - http://biorxiv.org/content/early/2020/11/27/2020.11.25.399139.short 4100 - http://biorxiv.org/content/early/2020/11/27/2020.11.25.399139.full AB - 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 StatementThe authors have declared no competing interest.