Pulmonary Vascular Endothelialitis in COVID-19

Quick Takes

  • Lung autopsies from patients with COVID-19 demonstrate severe endothelial injury with intracellular virus.
  • Widespread vascular thrombosis with microangiopathy and occluded alveolar capillaries were common in COVID-19 lung autopsy specimens.
  • The role of thromboprophylaxis anticoagulation remains unclear given autopsy specimens in patients with COVID-19.

Study Questions:

What are the associated morphologic and molecular changes in the lung vasculature of patients who die from coronavirus disease 2019 (COVID-19)?

Methods:

Autopsy specimens obtained from seven patients who died from COVID-19 were compared with autopsy specimens from patients who died from acute respiratory distress syndrome secondary to influenza A (H1N1) and 10 age-matched, uninfected controls. The lungs of each autopsy specimen were studied using macroscopic and microscopic imaging techniques, micro-computed tomographic imaging, scanning electron microscopy, and other techniques.

Results:

In patients who died from COVID-19 or H1N1 influenza, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The mean ± standard deviation weight of the lungs was higher for patients with H1N1 influenza than COVID-19 (2404 ± 560 g vs. 1681 ± 49 g, p = 0.04). The lungs of patients with COVID-19 also showed distinct vascular features, including severe endothelial injury associated with intracellular virus and disrupted cell membranes, including up to 10-fold higher ACE2 expression than uninfected lungs. Histologic analysis of the pulmonary vessels in patients with COVID-19 showed widespread thrombosis with microangiopathy (nine times more common in patients with COVID-19 as influenza, p < 0.001). Patients with COVID-19 also had 2.7 times as much new vessel growth (predominately intussusceptive angiogenesis) as patients with H1N1 influenza (p < 0.001).

Conclusions:

The authors concluded that their small series of lung autopsy specimens identified a distinct pattern of angiogenesis in patients with COVID-19 as compared to patients with H1N1 influenza.

Perspective:

This autopsy series outlines three distinctive findings among patients who died from COVID-19: 1) severe endothelial injury with intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and disrupted cell membranes, 2) widespread vascular thrombosis with microangiopathy and occlusion of alveolar capillaries, and 3) significantly higher new vessel growth than non-COVID-19 lungs. Of note, the widespread thrombosis noted on autopsy was microscopic and suggests both in situ and potentially inflammatory-mediated processes. These raise important thromboprophylaxis and therapy questions about the efficacy of anticoagulants, which are used largely based on their efficacy in macrothrombosis and embolic disease.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Heart Failure and Cardiac Biomarkers, Computed Tomography, Nuclear Imaging

Keywords: Anticoagulants, Autopsy, Capillaries, Coronavirus, COVID-19, Diagnostic Imaging, Geriatrics, Influenza A Virus, H1N1 Subtype, Influenza, Human, Lung Injury, Microscopy, Electron, Scanning, Peptidyl-Dipeptidase A, SARS Virus, Secondary Prevention, severe acute respiratory syndrome coronavirus 2, Tomography, X-Ray Computed, Vascular Diseases, Venous Thromboembolism


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