Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

By M. Ackermann, S. Verleden, M. Kuehnel, A. Haverich, T. Welte, F. Laenger, A. Vanstapel, C. Werlein, Helge Stark, A. Tzankov and 4 more. New England Journal of Medicine, 2020

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BACKGROUND Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. METHODS We examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immunohistochemical analysis, micro–computed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression. RESULTS In patients who died from Covid–19-associated or influenza-associated respiratory failure, the histologic pattern in the peripheral lung was diffuse alveolar damage with perivascular T-cell infiltration. The lungs from patients with Covid-19 also showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels in patients with Covid-19 showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi were 9 times as prevalent in patients with Covid-19 as in patients with influenza (P<0.001). In lungs from patients with Covid-19, the amount of new vessel growth — predominantly through a mechanism of intussusceptive angiogenesis — was 2.7 times as high as that in the lungs from patients with influenza (P<0.001). CONCLUSIONS In our small series, vascular angiogenesis distinguished the pulmonary pathobiology of Covid-19 from that of equally severe influenza virus infection. The universality and clinical implications of our observations require further research to define. (Funded by the National Institutes of Health and others.)

Subfields: Infectious Diseases, Neurology, Pulmonary and Respiratory Medicine

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Citations in the corpus

COVID-19 and the human innate immune system (2021, background): “Furthermore, the virus facilitates the release of coagulation factors, the secretion of inflammatory cytokines, and the formation of leukocyte-platelet aggregates, which might be important mechanisms leading to thromboembolic complications observed in severe COVID-19 (Ackermann et al., 2020; Gupta e”
COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection (2021, background): “To further determine the SARSCoV-2-mediated cytopathic effects on different organs, autopsy studies provided compelling evidences on diffuse alveolar damage with activated type II pneumocytes, fibroblasts, protein-rich exudate, hyaline membrane, and infiltrating lymphocytes in the wall of pulmonary ”
Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis (2020, background): “org Volume 130 Number 11 November 2020 Introduction Accumulated clinical evidence during the evolving coronavirus 2019 (COVID-19) pandemic indicates that severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) infection triggers thrombotic complications that affect multiple vital organs, increa”
COVID-19 is, in the end, an endothelial disease (2020, background): “IL-1 not only induces leucocyte adhesion molecules but, by reducing VE-cadherin production, can contribute to impaired endothelial barrier function and thus capillary leak, a major issue that complicates COVID-19 pneumonitis.47 Agents that inhibit the inflammasome–IL-1b–IL-6 pathway may thus compris”