Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations

Abstract

Rationale: Clinical and epidemiologic data in coronavirus disease (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 (CT) pulmonary angiography [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 and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography. Measurements and Results: In 39 consecutive patients (male: female, 32:7; mean age, 53 6 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 6 14.7 ml/cm H 2 O; Murray lung injury score, 3.14 6 0.53; mean ventilatory ratios, 2.6 6 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (6SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 6 16.7%, 36.3 6 24.7%, and 42.7 6 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.

Early experience with critically ill patients with COVID-19 in Montreal

“…Moreover, signs of widespread capillary angiopathy were recently shown on computed tomography (CT) pulmonary angiography and dual-energy CT in patients with severe COVID-19. 30 The increased dead space, in conjunction with the hyperinflammatory profile with repeated febrile episodes, resulted in the persistent need for high minute ventilation in a significant proportion of IMV patients. This manifested as relentless air hunger whenever neuromuscular blockers and sedation were weaned, as illustrated by the relatively high P 0.1 despite high opiate doses in patients on IMV for more than a week.…”

“…The median [IQR] day 1 sequential organ failure assessment score was 6 [3][4][5][6][7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] mL/ cmH 2 O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53-0.67]; day 10 = 0.72 [0.69-0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients.…”

Response to Damiani and colleagues

“…We have read with great interest the comment of Damiani on our article, retaining the hypothesis of a possible major role of microvascular derangement in the physiopathology of COVID-19 ARDS. Such a hypothesis, supported by a number of arguments such as the rich expression of the SARS-CoV-2 ACE2 receptors in lung endothelial cells and dysregulation of the renin-angiotensin system, is now widely mentioned by others, using different approaches such as EIT studies [1], high-energy CT studies [2] and histopathology studies [3].…”

Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia

“…Vascular enlargement has been a common radiographical finding 22 . A recent study highlighted the prevalence of perfusion defects affecting large lung fractions in mechanically ventilated patients with severe COVID-19, as well as dilation of peripheral vessels 30 . Thus, there is strong clinical evidence of vascular dysregulation in the lungs, and there may be potential for poorly aerated injured regions to exhibit at least impairment of HPV if not vasodilation.…”