Abstract
In 2019, a new strain of coronavirus, severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China. Nearly 25 million cases have since been reported in the US and almost 500,000 Americans have died. The aggressive inflammatory response of the host to SARS-CoV-2 infection plays a significant role in disease severity. Severe SARS-CoV-2 infection often leads to Acute Respiratory Distress Syndrome (ARDS), Severe Inflammatory Response Syndrome (SIRS), and Cytokine Release Syndrome (CRS). Observed in about a third of fatal COVID-19 patients, CRS is correlated to high mortality. Patients experiencing CRS also suffer from systemic vascular dysfunction. Thus, methods to assess endothelial cell function may prove essential to evaluate effectiveness of therapeutic interventions targeting cytokines. Our objective was to characterize dynamic responses of vascular endothelial cell monolayer barrier resistance (Rb) when treated with COVID-19 related cytokines. We quantified the effect of eight different cytokines to induce Rb changes in human aortic endothelial cell (HAoEC) monolayers using Electric Cell-substrate Impedance Sensing. We found that Rb of HAoEC monolayers was significantly reduced when treated with TNF-α, IL-1β, or IFN-γ compared to untreated controls. In the case of TNF-α, no significant difference in Rb was measured in cell monolayers treated with TNF-α and anti-TNF-α monoclonal antibody. On the other hand, anti-IL-1β antibody did not block the effect of IL-1β which induced a significant reduction in Rb compared to cytokine free controls. A significant reduction in Rb values were also noted in cell monolayers treated with TNF-α and IL-1β combinations suggesting a systemic synergistic effect.
