Mount Sinai Study Finds COVID-19 May Be Driven by Pulmonary Thrombi and Pulmonary Endothelial Dysfunction
A new study from the Icahn School of Medicine at Mount Sinai suggests that blood clots, especially in the lungs, may play a role in severe cases of COVID-19. The finding suggests that treatment for respiratory failure caused by COVID-19 might follow the model for stroke—anticoagulation drugs for milder cases and thrombolysis, or clot removal, with continued anticoagulation for more severe disease.
The researchers found that critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical acute respiratory distress syndrome (ARDS), but one that is more consistent with pulmonary vascular disease.
SARS-CoV-2, the virus that causes COVID-19, is closely related to SARS-CoV-1, the virus that caused the SARS outbreak in 2003. Previous autopsy studies from SARS cases demonstrated pulmonary thrombi, pulmonary infarcts, and microthrombi in other organs. Pulmonary thrombi are blood clots in the lungs that can cause pulmonary infarcts, the death of lung tissue due to lack of blood supply. Now, studies show that SARS-CoV-2 appears to be causing similar pathophysiological derangements. Although microthrombi, clots in small blood vessels, are present in sepsis and classic forms of ARDS, they are not the principal drivers of respiratory failure and organ dysfunction in those cases. In COVID-19 pneumonia, the thrombi may play a direct and significant role in gas exchange abnormalities and in multisystem organ dysfunction, the Mount Sinai researchers said.
The researchers observed five cases of COVID-19 patients at Mount Sinai Health System hospitals with refractory respiratory failure requiring mechanical ventilation and shock. Significant pulmonary microthrombi and/or macrothromboses were suspected to be serving as drivers of this pre-terminal state. The patients were administered tPA, a thrombolyic agent used to dissolve blood clots. All cases showed rapid improvement in alveolar ventilation, oxygenation, and/or shock.
These five cases had respiratory failure early in their COVID-19 course along with evidence of the “pulmonary vascular” phenotype, such as elevated protein fragments that are produced when a blood clot gets dissolved in the body and increased dead space, or air that is inhaled but does not take part in the gas exchange. Based on these findings, the researchers said, it may be prudent to consider full systemic anticoagulation—medication that is used to prevent the formation of blood clots—to mitigate disease progression in early stages and thrombolysis, in which clots are dissolved using thrombolytic agents, such as tPA, for more serious cases.
“It seems that for at least a significant subset of these patients, the underlying driver of respiratory failure and organ dysfunction is actually thrombosis and endothelial dysfunction,” said Hooman Poor, MD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai. “Future clinical trials will need to evaluate the role of anticoagulation for milder disease and thrombolysis for more severe disease.”
The high prevalence of obesity, hypertension, and diabetes in patients with severe COVID-19 pneumonia may point to an underlying susceptibility to endothelial injury and dysregulation, in which the inner lining of the small arteries fails to perform all of its important functions. The researchers advise that these therapeutic approaches should be considered in the management of COVID-19 patients and must be further examined in clinical research studies.
The Icahn School of Medicine at Mount Sinai, a top-ranked academic medical center in New York City, and National Jewish Health, the nation’s leading respiratory hospital based in Denver, Colorado, have partnered to create the Mount Sinai – National Jewish Health Respiratory Institute. To learn more about the Mount Sinai – National Jewish Health Respiratory Institute, visit our website, Facebook, or Twitter.
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