SUMMARY
The authors characterized cellular and humoral immunity in a cohort of 203 patients with acute moderate or severe COVID-19, convalescent phase after asymptomatic/mild or severe COVID-19, and healthy volunteers from Sweden. T cells were shown to display an activated/cycling phenotype, whereas convalescent phase SARS-CoV-2-specific CD8 T cell populations were skewed toward an early differentiated memory phenotype. SARS-CoV-2-specific T cells acquired an early differentiated memory phenotype with higher proliferation and polyfunctionality in the convalescent phase. SARS-CoV-2-specific T cells were also shown to generate anamnestic responses to cognate antigens in the convalescent phase.
Memory T cell responses were detected in exposed healthy individuals lacking detectable circulating antibodies, indicating that seroprevalence alone could underestimate population immunity.
...Of note, we detected cross-reactive T cell responses against spike or membrane in 28% of the unexposed healthy blood donors, consistent with a high degree of preexisting immune responses potentially induced by other coronaviruses (Braun et al., 2020; Grifoni et al., 2020; Le Bert et al., 2020).
Although we detected generally broader and stronger T cell responses in seronegative convalescent and exposed individuals compared to unexposed donors, it remains possible that a fraction of the anamnestic SARS-CoV-2-specific T cell response was initially induced by seasonal coronaviruses (Mateus et al., 2020). The biological relevance of cross-reactive T cell responses remains unclear. However, it is tempting to speculate that such responses may provide at least partial protection against SARS-CoV-2, and different disease severity, given that pre-existing T cell immunity has been associated with beneficial outcomes after challenge with the pandemic influenza virus strain H1N1 (Sridhar et al., 2013; Wilkinson et al., 2012).
Collectively, our data provide a functional and phenotypic map of SARS-CoV-2- specific T cell immunity across the full spectrum of exposure, infection, and disease. The observation that many individuals with asymptomatic or mild COVID-19, after SARS-CoV-2 exposure or infection, generated highly durable and functionally replete memory T cell responses, not uncommonly in the absence of detectable humoral responses, further suggests that natural exposure or infection could prevent recurrent episodes of severe COVID-19.