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 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.

Early T cell and binding antibody responses are associated with COVID-19 RNA vaccine efficacy onset

“…Efforts to identify the correlates of protection are being made by measuring the adaptive immune response longitudinally in convalescent COVID-19 cases, which has been shown to contain a spectrum of both humoral and cellular responses. 5 , 6 , 7 Without a sizeable proportion of cases with repeat episodes of COVID-19, however, teasing apart these adaptive immune responses to identify the elements minimally required for protection will be challenging. Similar challenges apply to identifying breakthrough infection among vaccinated subjects, given the high level of vaccine efficacy.…”

“…SARS-CoV-2-specific T cells were tested as described previously. 7 Briefly, cryopreserved PBMC were thawed and directly tested by IFN-γ-ELISpot for reactivity to a pool of 55 peptides covering the immunogenic regions of the SARS-CoV-2 S-protein (S pool) which spans 40.5% of the whole SARS-CoV-2 S-protein. ELISpot plates (Millipore) were coated with human IFN-γ antibody overnight at 4°C.…”

“…320 μL of whole blood drawn on the same day were mixed with 80 μL RPMI and stimulated with pools of the SARS-CoV-2 S-peptides at 2 μg/ml or a DMSO control as described. 7 After 16 hours of culture, the culture supernatant (plasma) was collected and stored at −80°C until quantification of cytokines. Cytokine concentrations in the plasma were quantified using an Ella machine with microfluidic multiplex cartridges measuring IFN-γ following the manufacturer’s instructions (ProteinSimple).…”

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naïve and COVID-19 recovered individuals

“…SARS-CoV-2 peptide pools of 15-mers (55 peptides) covering 40.5% of the Spike protein and contain most of the SARS-CoV2 spike epitope published to date [10] were used as reported in [7]…”

“…The complexity of monitoring virus-specific T cell magnitude and function has so far prevented the full characterization of the immune cellular response to the vaccine. To address this problem, we have shown that SARS-CoV-2-specific T cells (both CD4 helper and CD8 cytotoxic) can be reliably quantified in both SARS-CoV-2 infected individuals [7] and vaccine recipients [11] by a direct and quantitative ex vivo measurement of IFN-gamma secreted by whole blood samples stimulated with a pool of viral peptides.…”