“We see similar effects on patients with a chronic HIV infection with increased level of exhausted CD57+ CD8+ T cells.”..
SARS-CoV-2 induces a long-term altered exhausted CD57+CD8+ T cell population
To investigate the magnitude of T cell impairment during SARS-CoV-2 infection and recovery, we measured the frequency of co-inhibitory markers that are normally upregulated during exhaustion and suppression on bulk CD3+, CD4+ and CD8+ T cell subsets. CD57 is a marker of terminally differentiated, non-proliferative T cells (senescence and exhaustion) and the frequency of CD57+CD4+ and CD57+CD8+ T cells increases with age as well as with cancer and chronic infections. Dimensionality reduction showed stronger CD57 expression across bulk CD3+ cells at all-time points.
Both CD4+ and CD8+ T cell populations were examined for expression of CD57 as shown by a representative pseudo color dot plot. We found no significant difference in the proportion of CD57+CD4+ T cells between COVID-19 patients and healthy controls. Interestingly, we observed a significant surge in the percentage of CD57+CD8+ T cells among COVID-19 patients at inclusion compared to healthy controls, which increased further by the 6 week time point and was sustained up until 6-7 months. Taken together, our data clearly shows a long-lasting effect on the CD8+ T cell population with increased level of exhausted CD57+ CD8+ T cells.
“Our findings suggest that once T cells become exhausted, they remain fundamentally ‘wired’ to be exhausted—thus it may be hard to get them to become effective virus- and cancer-fighters again,” – E. John Wherry, PhD
