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Synergistic Role of NK Cells and Monocytes in Promoting Atherogenesis in Severe COVID-19 Patients.

Gunasena, M.; Alles, M.; Wijewantha, Y.; Mulhern, W.; Bowman, E.; Gabriel, J.; Kettelhut, A.; Kumar, A.; Weragalaarachchi, K.; Kasturiratna, D.; Horowitz, J. C.; Scrape, S.; Pannu, S. R.; Liu, S.-L.; Vilgelm, A.; Wijeratne, S.; Bednash, J. S.; Demberg, T.; Funderburg, N. T.; Liyanage, N.

2023-11-12 infectious diseases
10.1101/2023.11.10.23298322 medRxiv
Show abstract

Clinical data demonstrate an increased predisposition to cardiovascular disease (CVD) following severe COVID-19 infection. This may be driven by a dysregulated immune response associated with severe disease. Monocytes and vascular tissue resident macrophages play a critical role in atherosclerosis, the main pathology leading to ischemic CVD. Natural killer (NK) cells are a heterogenous group of cells that are critical during viral pathogenesis and are known to be dysregulated during severe COVID-19 infection. Their role in atherosclerotic cardiovascular disease has recently been described. However, the contribution of their altered phenotypes to atherogenesis following severe COVID-19 infection is unknown. We demonstrate for the first time that during and after severe COVID-19, circulating proinflammatory monocytes and activated NK cells act synergistically to increase uptake of oxidized low-density lipoprotein (Ox-LDL) into vascular tissue with subsequent foam cell generation leading to atherogenesis despite recovery from acute infection. Our data provide new insights, revealing the roles of monocytes/macrophages, and NK cells in COVID-19-related atherogenesis.

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