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

Our take —

In a small autopsy study, lungs from COVID-19 patients demonstrated similar diffuse alveolar damage with immune cell infiltration as is typically seen with influenza. However, COVID-19 lungs also had evidence of notable blockage of the vessels with rampant new vascular development. This may be a key pathogenic feature of the disease, and may correlate with the large vessel disease observed in epidemiologic studies. Further research is needed to better describe the pathophysiology and its implications.

Study design

Case Series; Case-Control

Study population and setting

The study consisted of pulmonary autopsy specimens at the Hannover Medical School in Hannover, Germany, from seven patients who died from respiratory failure due to laboratory-confirmed SARS-CoV-2 infection. There were two sets of comparison specimens: lungs from seven age, sex, and severity matched patients who died of influenza A H1N1 virus infection, and lungs from ten uninfected patients. None of the COVID-19 patients received mechanical ventilation while five of seven patients with influenza received mechanical ventilation. Pulmonary specimens underwent detailed CT and electron microscopy imaging, staining, and gene-expression analysis.

Summary of Main Findings

All COVID-19 lung specimens had evidence of diffuse alveolar damage with widespread T-cell infiltration, as did the influenza-positive specimens. ACE-2 enzyme expression was elevated in both COVID-19 and influenza-positive lungs compared to uninfected controls. In both COVID-19 and influenza-positive lungs, four of seven specimens had evidence of precapillary thrombi. However, alveolar capillary microthrombi were nine times as common in the COVID-19 specimens compared to the influenza-positive specimens. Notably, there was much more evidence of distorted vasculature with significant new, nonsprouting vascular growth in COVID-19 specimens compared to both of the comparison specimens.

Study Strengths

The study provided a comprehensive assessment of both gross pathology and microvascular structure with gene-expression profiles.

Limitations

There was a very small sample size. The COVID-19 patients were considerably older than influenza patients (median age 78 versus 53 years). There appear to have been notable differences in the clinical course and clinical care between the influenza and COVID-19 patients, which may underlie some of the pathologic differences observed.

Value added

This is among the most detailed pathologic analyses of COVID-19 lung specimens to date. It highlights rampant and distorted angiogenesis that may be a key feature of disease pathogenesis.

This review was posted on: 6 July 2020