Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

Chioh, F. W.; Fong, S.-W.; Young, B.; Wu, K.-X.; Siau, A.; Krishnan, S.; Chan, Y.-H.; Teo, L. L.; Gao, F.; Tan, R. S.; Zhong, L.; Koh, A. S.; Tan, S. Y.; Tambyah, P. A.; Renia, L.; Ng, L. F. P.; Lye, D. C. B.; Cheung, C.

The rapid rise of coronavirus disease 2019 patients who suffer from vascular events after their initial recovery is expected to lead to a worldwide shift in disease burden. We aim to investigate the impact of COVID-19 on the pathophysiological state of blood vessels in convalescent patients. Here, convalescent COVID-19 patients with or without preexisting conditions (i.e. hypertension, diabetes, hyperlipidemia) were compared to non-COVID-19 patients with matched cardiovascular risk factors or healthy participants. Convalescent patients had elevated circulating endothelial cells (CECs), and those with underlying cardiovascular risk had more pronounced endothelial activation hallmarks (ICAM1, P-selectin or CX3CL1) expressed by CECs. Multiplex microbead-based immunoassays revealed some levels of cytokine production sustained from acute infection to recovery phase. Several proinflammatory and activated T lymphocyte-associated cytokines correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Finally, the activation markers detected on CECs mapped to the counter receptors (i.e. ITGAL, SELPLG, and CX3CR1) found primarily on CD8+ T cells and natural killer cells, suggesting that activated endothelial cells could be targeted by cytotoxic effector cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.