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

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)Nanyang Technological UniversityNational Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis research is funded by National Medical Research Council (COVID19RF-001, COVID19RF-060, NMRC/TA/0031/2015, MOH-000153, NMRC/OFIRG/0018/2016, NMRC/BnB/0017/2015, MOH-000358), Biomedical Research Council, A*STAR (H20/04/g1/006), National Research Foundation Singapore (NRF2017_SISFP09), Nanyang Technological University (Nanyang Assistant Professorship Start-Up Grant), Ministry of Education - Singapore (MOE2018-T2-1-042) and Agency for Science, Technology and Research (H18/01/a0/017)