Cytokine storm in COVID-19 may drive T-cell depletion, exhaustion
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Uncontrolled cytokine release, also known as cytokine storm, may prompt the depletion and exhaustion of T cells observed among patients with COVID-19, according to data published in Frontiers in Immunology.
“Our study revealed the main subpopulation of T cells are generally depleted and functionally exhausted in COVID-19 patients, particularly in severe cases,” Yongwen Chen, PhD, of the Third Military Medical University, in Chongqing, China, told Healio Rheumatology. “It also suggests that coronavirus does not attack T cells directly, but rather triggers the cytokine release, which then drives the depletion and exhaustion of T cells.”
To investigate the factors that may cause T-cell reductions among patients with COVID-19, as well as to compare the expression of exhaustion markers among confirmed cases and healthy controls, Chen and colleagues analyzed data from 522 patients with the disease in Wuhan, China. These patients ranged in age from 5 days to 97 years, and had been admitted to either the General Hospital of Central Theater Command or Hanyang Hospital, both in Wuhan. Investigators recruited a control group of 40 healthy participants from individuals who reported to the hospitals for routine physical examinations.
For their retrospective analysis, Chen and colleagues reviewed clinical and nursing records, laboratory results, chest X-rays and CT scans for all patients with COVID-19, as well as physical examination records for the control participants. Also, peripheral blood samples from 14 patients with COVID-19 and three healthy volunteers were simultaneously processed at the General Hospital of Central Theater Command to isolate peripheral blood mononuclear cells (PBMCs) for additional testing.
According to the researchers, the number of total T cells, CD4+ and CD8+ T cells were dramatically reduced among patients with COVID-19, particularly in those who required intensive care. Total T-cell, CD8+ T-cell or CD4+ T-cell counts lower than 800, 300, or 400/L, respectively, were negatively correlated with patient survival. Further, T-cell counts were negatively associated with serum IL-6, IL-10 and TNF-alpha concentrations. Patients in the disease resolution period demonstrated decreased IL-6, IL-10 and TNF-alpha concentrations and restored T cell counts.
T cells among patients with COVID-19 also had significantly higher levels of the exhausted marker PD-1. The researchers noted increasing PD-1 and Tim-3 expression on T cells among patients as they progressed from prodromal to overtly symptomatic disease stages.
“We found that T cell number reduction is earlier than the clinical signs, suggesting that more urgent, early intervention may be required in patients with low T lymphocyte counts” Chen said. “Because of T cell depletion and exhaustion, the patients are more vulnerable to secondary infection, so the meticulous nursing care and anti-infection treatment may be in consideration. The findings offer clues on how to target treatment for COVID-19.”
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