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Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience

Our take —

This paper was a preprint and thus was not yet peer reviewed. Findings from this interdisciplinary autopsy series of 67 SARS-CoV-2 positive patients suggest endothelial dysfunction and hypercoagulability in several major organs, as well as immune dysfunction. These results provide support for previous studies suggesting key roles of endothelial damage and abnormal macrophage activation in severe COVID-19 disease. More research into potential mechanistic pathways will be key to identifying effective therapeutic strategies.

Study design

Case Series

Study population and setting

This study includes 67 consecutive autopsies on SARS-CoV-2 positive patients performed at Mount Sinai Hospital between March 20 and April 29, 2020. Mount Sinai Hospital performs all autopsies for each of the seven hospitals in the Mount Sinai Health System in New York City. The study reports on lab values for 49 patients and autopsy findings specific to several organ systems: lungs (n=25), thoracic lymph node (n=11), heart (n=25), bone marrow (n=6), spleen (n=22), kidney (n=25), liver (n=22), gastrointestinal organs (n=20), brain (n=35).

Summary of Main Findings

The median age of patients was 69 years (range 34-94), with an average time from admission to death of 9.5 days (range 0-61). Levels of Inflammatory markers (i.e. ferritin, C-reactive protein, procalcitonin, and white blood cell count), d-dimer (despite 81% of patients receiving anticoagulation therapy), interleukin-6, interleukin-8, and TNFa were all higher than the reference levels. The predominant lung findings were diffuse alveolar damage in 22/25 cases and aggregates/thrombi of medium-sized arteries, arterioles, and capillaries in 23/25 cases. Microthrombi were present in several other organ systems, including the brain, lymph, heart, and liver. Endothelial dysfunction was also common, evidenced by high levels of ACE2 expression in lung and brain parenchymal capillaries. Presence of hemophagocytic histiocytes found in lymph nodes, spleen, bone marrow, heart, and liver support previous conjectures about macrophage activation syndrome in COVID-19 patients.

Study Strengths

Compared to existing autopsy studies, the sample size is relatively large (though varies by organ system). The autopsies include comprehensive laboratory and imaging analyses.

Limitations

The clinical and demographic characteristics of patients with available tissue for each autopsy is not available. Autopsy findings were not linked to clinical characteristics. The study includes only adult patients, so findings cannot be generalized to children or adolescents, who may have different disease presentations.

Value added

The is the largest autopsy study to date with data on several major organ systems, suggesting potential mechanisms for some of the more puzzling clinical symptoms in patients with severe COVID-19 disease.