The Effect of COVID-19 on Natural Killer Cell Function
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2024-06-26
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COVID-19 has caused more than 7 million deaths, and according to the World Health Organization, it continues to result in more than 1000 reported deaths per week at the time of this writing. Therefore, it is crucial to understand the immune response to COVID-19 since the virus has the potential to become endemic, like influenza A. Natural killer (NK) cells are essential for immune defence against viral infections and play a critical role in COVID-19. While it is well documented that infected patients have a reduction in lymphocytes and NK cells, gaps in knowledge exist regarding the function of NK cells. To study the function of NK cells in COVID-19 patients, peripheral blood was obtained from patients admitted to the medical (non-ICU) wards at the Foothills Medical Centre with a positive COVID-19 test. I demonstrated a decrease in the mature cytotoxic subset of NK cells within the peripheral blood of patients hospitalized with COVID-19. I also observed a notable decrease in the cytotoxic function of NK cells against tumour targets. I examined the sequence of events within NK cells that lead to killing in a stepwise manner. I found reductions in the intracellular levels of effector molecules, the degranulation of cytotoxic granules, and the extracellular concentrations of released effector molecules. I identified alterations in intracellular granule trafficking required to position the granules for release. I found alterations in the expression of multiple NK cell receptors, suggesting inhibitory signalling. Additionally, males with COVID-19 showed more pronounced NK cell defects than healthy males, which may partly be due to receptor expressions. My findings highlight defects in cytolytic effector molecules, granule trafficking and release, and increased expression of inhibitory receptors in hospitalized COVID-19 patients, in addition to a sex difference in cytolytic function, which contributes to defective NK cell function in COVID-19.
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Dagar, A. (2024). The effect of COVID-19 on natural killer cell function (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.