The Lab: “Dysfunctional Metabolism of T Cells in Collegiate Football Players with SARS-CoV2”

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent of COVID19, which caused a global pandemic. One of the pathogenic hallmarks of COVID19 is a dysregulation of immune cell metabolism accompanied by excessive inflammatory cytokine response, particularly in adults with underlying co-morbidities. However, the impact of SARS-CoV2 on metabolic function in discrete cellular populations, such as T cells, in young, otherwise healthy, elite-level athletes who recovered from COVID19 is currently unknown.

PURPOSE: We examined whether NCAA Division I Football Players exhibited altered T cell metabolism after recovering from COVID19.

METHOD: We studied 9 PCR SARS-CoV2 post-positive (COVID19+) collegiate football players following 14-day quarantine and 4 COVID19 naïve players(COVID19-). Resting T cells were isolated and stimulated overnight with either: 1) SARS-CoV2peptivator pool of S + N + M peptides (JPT peptides), 2) T cell activator beads CD3/CD28, 3)S ARS-CoV2 peptides+CD3/CD28 beads, or 4) T cells alone. Following overnight stimulation, T-cell bioenergetics were characterized using the Seahorse Bio Analyzer (Agilent) to measure extracellular acidification rates (ECAR, a measure of glycolysis) and oxygen consumption rates (OCR, a measure of mitochondrial bioenergetics). Differences between groups were analyzed using ANOVA and Dunnett’s post hoc tests.

RESULTS: The ECAR of T cells isolated fromCOVID19+ participants was 32.5% lower when activated with CD3/CD28 beads and the SARS-CoV2 peptides, than that of T cells activated with beads alone (p < 0.05), but no difference was observed in T cells from COVID19- controls (p > 0.05). Similarly, OCR associated with ATP production was also 32.7% lower in COVID19+ participants (p < 0.001) when stimulated withSARS-CoV2 peptides, but not in COVID19- participants (p > 0.05).

DISCUSSION: Our data suggest that SARS-CoV2 infection is associated with impaired T cell bioenergetics, which could detrimentally impact T cell effector functions. As such, SARS-CoV2 infection appears to be associated with hallmarks of T cell exhaustion even in elite collegiate athletes, which would be exacerbated in adults with pre-existing metabolic diseases (i.e., diabetes, obesity) and other co-morbidities.

RESEARCHERS

Cho, E., Axelrod, C., Kerwin, J., Granger, J., H., Irving, B., Johannsen, N., Spielmann, G.