Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of endothelial dysfunction associated with higher risk of mortality. However, it is unclear whether endothelial dysfunction is caused by direct infection of endothelial cells or is mainly secondary to inflammation. Here, we investigate whether different types of endothelial cells are susceptible to SARS-CoV-2.

Methods: Human endothelial cells from different vascular beds including umbilical vein endothelial cells, coronary artery endothelial cells (HCAEC), cardiac microvascular endothelial cells, lung microvascular endothelial cells, and pulmonary arterial cells isolated from diabetics were inoculated in vitro with SARS-CoV-2 and analyzed 5 days post infection. Human colon carcinoma cells (CaCo2), which are highly permissive for SARS-CoV-2, served as positive control.

Results: Spike protein expression was detected in HCAECs after SARS-CoV-2 infection but not in the other endothelial cells tested. Mimicking pro-inflammatory conditions by exposing the endothelial cells to tumor necrosis factor-α did not result in increased spike protein and even reduced presence of spike protein in HCAEC. Infection of living human heart slices further confirmed that microvascular endothelial cells are not susceptible to the virus in a cardiac environment ex vivo. Consistently, only HCAEC expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2), required for virus infection, protein. Despite this, no intracellular double stranded viral RNA was detected in HCAECs and the supernatant did not contain infectious virus. Analysis of the cellular distribution of the spike protein revealed that it co-localized with endosomal calnexin, suggesting that SARS-CoV-2 is entering but trapped in HCAECs. SARS-CoV-2 infection also did not induce cytotoxic effects and did not augment pro-inflammatory genes in HCAECs.