![]() ![]() The frequency of baseline cross-reactive T cells is correlated with the infection outcome following SARS-CoV-2 exposure, and we observe significantly higher frequencies of cross-reactive memory T cell responses in PCR-negative contacts. We quantify T cells specific for in silico-predicted and biologically confirmed pools of cross-reactive epitopes from 5 SARS-CoV-2 proteins, alongside protein-spanning peptide pools, using a highly sensitive dual cytokine fluorescence-linked immunospot (FLISpot) assay to detect both IFN-γ and interleukin-2 (IL-2). Here we assess contacts of newly diagnosed COVID-19 cases to capture the earliest time-points after SARS-CoV-2 exposure. ![]() However, no study yet describes an association of cross-reactive T cells with outcome after SARS-CoV-2 exposure. Studies to date have described the prevalence of SARS-CoV-2 cross-reactive T cells in naive healthy controls 1, 2, 3, 4 and in hospitalised COVID-19 patients 5, 6. Exposure to SARS-CoV-2 does not universally result in infection and pre-existing T cells, primed by endemic human coronaviruses (huCoVs), might mediate protection in SARS-CoV-2-naive persons. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.ĭespite mass deployment of effective vaccines against SARS-CoV-2, correlates of protection against infection remain unknown. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26) no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Nature Communications volume 13, Article number: 80 ( 2022)Ĭross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts ![]()
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