Under imbalanced stress conditions, there are evident cumulative systemic effects leading to chronic inflammation including but not restricted to the lasting vasospastic reactions with systemic ischemic-hypoxic effects and involvement of ET-1 and neuro-immune axes, mitochondrial impairments and increased infection susceptibility with poor outcomes such as caused by the cytokine storm reported for COVID-19-infected individuals [19, 22]. Here, EDN1 is linked to COVID-19.