Pulmonary Vascular Endothelialitis in COVID-19

Jul 09, 2020
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Authors:
Ackermann M, Verleden SE, Kuehnel M, et al.
Citation:
Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 2020;383:120-128.
Summary By:
Geoffrey D. Barnes, MD, MSc, FACC

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, COVID-19 Hub, Geriatric Cardiology, Noninvasive Imaging, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, 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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