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

Le Bert, N.; Clapham, H. E.; Tan, A. T.; Chia, W. N.; Tham, C. Y.; Lim, J. M.; Kunasegaran, K.; Tan, L.; Dutertre, C.-A.; Shankar, N.; Sun, L. J.; Zahari, M.; Tun, Z. M.; Kumar, V.; Lim, B. L.; Lim, S. H.; Chia, A.; Tan, Y.-J.; Tambyah, P. A.; Kalimuddin, S.; Lye, D. C.; Low, J. G.; Wang, L.-F.; Wan, W. Y.; Hsu, L. Y.; Bertoletti, A.; Tam, C. C.

doi:10.1101/2020.11.25.399139

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bioRxiv · 10.1101/2020.11.25.399139

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

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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-{gamma}, IL-4, IL-6, IL-1{beta}, TNF- 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-{gamma} 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- and IL-1{beta}) 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.

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Le Bert, N., Clapham, H. E., Tan, A. T., Chia, W. N., Tham, C. Y., Lim, J. M., Kunasegaran, K., Tan, L., Dutertre, C.-A., Shankar, N., Sun, L. J., Zahari, M., Tun, Z. M., Kumar, V., Lim, B. L., Lim, S. H., Chia, A., Tan, Y.-J., Tambyah, P. A., Kalimuddin, S., Lye, D. C., Low, J. G., Wang, L.-F., Wan, W. Y., Hsu, L. Y., Bertoletti, A., Tam, C. C.. 2020-11-27. Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. https://doi.org/10.1101/2020.11.25.399139

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