Rationale: Clinical and epidemiologic data in coronavirus disease 2019 (Covid-19) have accrued rapidly since the outbreak but few address the underlying pathophysiology. Objectives: To ascertain the physiologic, hematologic and imaging basis of lung injury in severe Covid-19 pneumonia. Methods: Clinical, physiologic and laboratory data were collated. Radiologic (computed tomography pulmonary angiography [CTPA, n=39] and dual-energy CT [DECT, n=20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence/extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography (TEG). Measurements and Results: In 39 consecutive patients (M:F 32:7; mean age, 53±10 years [range 29-79 years]; black and ethnic minority, n=25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead-space (dynamic compliance, 33.7±14.7 mls/cmH2O; Murray Lung Injury Score, 3.14±0.53; mean ventilatory ratios, 2.6±0.8) with evidence of hypercoagulability and fibrinolytic ‘shutdown’. The mean CT extent (±SD) of normally-aerated lung, ground-glass opacification and dense parenchymal opacification were 23.5±16.7%, 36.3±24.7% and 42.7±27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]), were present in all patients (wedge-shaped, n=3; mottled, n= 9; mixed pattern, n=6). Conclusions: Physiologic, hematologic and imaging data show not only the presence of a hypercoagulable phenotype in severe Covid-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.