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. 2020 May 14;M20-2566.
doi: 10.7326/M20-2566. Online ahead of print.

Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series

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Free PMC article

Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series

Sigurd F Lax et al. Ann Intern Med. .
Free PMC article

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.

Objective: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.

Design: Prospective autopsy study.

Setting: Single pathology department.

Participants: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).

Measurements: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.

Results: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.

Limitation: The sample was small.

Conclusion: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.

Primary funding source: None.

Figures

Figure 1.
Figure 1.
Pulmonary thrombosis. A. A cross-section through the lung shows massive thrombosis of medium-sized to large arteries (arrows). B. A peripheral artery and its branches (arrows) are obliterated by thrombosis, and the supplied region is infarcted (asterisks). Note the emphysematous changes in both lungs (formalin-fixed specimens).
Figure 2.
Figure 2.
Stages of diffuse alveolar damage. A. Early, with edema and hyaline membranes (original magnification, × 100). B. Intermediate, with proliferation of pneumocytes admixed with lymphocytes and neutrophils, organizing a residual hyaline membrane (original magnification, × 100). C. Late, with proliferation of fibroblasts (original magnification, × 200). Hematoxylin–eosin staining.
Figure 3.
Figure 3.
Thrombosis of pulmonary arteries of various size. A. Thrombosis of a dilated mid-sized pulmonary artery without subsequent infarction. The surrounding lung tissue is in part edematous (original magnification, × 10). B. A small pulmonary artery is obliterated by a thrombus, which is infiltrated by neutrophils (original magnification, × 100). C. Pulmonary artery with thrombosis and infarction and pneumonia of the surrounding lung tissue (original magnification, × 10; corresponding histology to Figure 1, B). D. Microthrombi of small arteries in areas of diffuse alveolar damage (original magnification, × 100). Hematoxylin–eosin staining.
Figure 4.
Figure 4.
Other involved organs. A. Thrombosis of a central vein with focal necrosis of liver cells at 6 hours. Macrovesicular steatosis and focal canalicular bile plugs (original magnification, × 100). B. Acute tubular injury showing necrosis and regeneration of the proximal tubules. Some tubules contain proteinaceous material (original magnification, × 200). C. Lymphocyte depletion of a hilar lymph node, with absence of germinal centers and dilated vessels and sinuses (original magnification, × 40). D. The same patient showed adrenocortical hyperplasia with a nodular pattern (original magnification, × 20). Hematoxylin–eosin staining.

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