As all these systems are potentially affected during the progression of severe COVID-19, we propose that disruption of the alveolar niche and abnormal function of ACE2 as a result of SARS-CoV-2 infection could directly and cell-autonomously precipitate the development of lung injury, acute inflammation, cardiovascular failure and thromboembolism, which are the hallmarks of severe COVID-1955. The gene discussed is ACE2; the disease is Thromboembolism.