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

 Nina Le Bert, Hannah E Clapham, Anthony T Tan, Wan Ni Chia, Christine YL Tham, Jane M Lim, Kamini Kunasegaran, Linda Tan, Charles-Antoine Dutertre, Nivedita Shankar, Joey ME Lim, Louisa Jin Sun, Marina Zahari, Zaw M Tun, Vishakha Kumar, Beng Lee Lim, Siew Hoon Lim, Adeline Chia, Yee-Joo Tan, Paul Anantharajah Tambyah, Shirin Kalimuddin, David CB Lye, Jenny GH Low, Lin-Fa Wang, Wei Yee Wan, Li Yang Hsu,  

View ORCID ProfileAntonio Bertoletti, Clarence C Tam

doi: https://doi.org/10.1101/2020.11.25.399139

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2020.11.25.399139v1.full.pdf

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.

https://www.biorxiv.org/content/10.1101/2020.11.25.399139v1