Study identifies cardiopulmonary contributors to death in COVID-19

An autopsy study of African Americans who died from COVID-19 in New Orleans has revealed that certain pulmonary and cardiac pathology likely contributed to severe disease and death in this patient population.

“We found that the small vessels and capillaries in the lungs were obstructed by blood clots and associated hemorrhage that significantly contributed to decompensation and death in these patients,” Richard Vander Heide, MD, PhD, professor and director of pathology research at Louisiana State University Health Sciences Center in New Orleans, said in a press release. “We also found elevated levels of D-dimers — fragments of proteins involved in breaking down blood clots. What we did not see was myocarditis, or inflammation of the heart muscle, that early reports suggested significantly contributes to death from COVID-19.”

For the study, which was published in The Lancet Respiratory Medicine, Vander Heide and colleagues performed autopsies on 10 African American patients aged 44 to 78 years who died due to COVID-19. Immunostaining, RNA labeling and electron microscopy were used to evaluate pulmonary and cardiac features.

Notably, all patients had at least one comorbidity, with hypertension being the most common. Many also had a history of obesity, insulin-dependent type 2 diabetes and chronic kidney disease.

“Our study presents a large series of autopsies within a specific demographic experiencing the highest rate of adverse outcomes within the United States,” Sharon Fox, MD, PhD, associate director of research and development in the department of pathology at Louisiana State University Health Sciences Center in New Orleans, said in the release.

All patients presented to the hospital approximately 3 to 7 days after developing a mild cough and fever of 38.3°C to 38.8°C with sudden respiratory decompensation just before arrival to the ED or sudden collapse at home. Bilateral ground-glass opacities consistent with acute respiratory distress syndrome were found on chest X-ray, where available.

In addition to thrombosis and microangiopathy in the small vessels and capillaries of the lung, the researchers noted features of diffuse alveolar damage, including hyaline membranes, even among patients who had not received ventilation, and individual cell necrosis without lymphocytic myocarditis. They also found no evidence of secondary pulmonary infection by microorganisms.

“The findings of diffuse alveolar damage and enlarged, atypical pneumocytes are consistent with autopsy reports from the first SARS epidemic, but the burden of small vessel pulmonary thrombi and platelet aggregation is a novel and important finding specific to SARS-CoV-2, and extends beyond what is typically seen in diffuse alveolar damage,” the researchers wrote. “These findings could suggest endothelial damage or platelet dysfunction within the pulmonary vasculature, as seen in reports of endotheliitis caused by SARS-CoV-2.”

Importantly, the results may help inform clinical decision-making for a patient population that is significantly affected by COVID-19 and likely has wider implications as well, according to the researchers.

“The key implications of our study include the discovery of a mechanism for severe pathology within the African American population, likely extendable to all persons with severe disease, and possibly a target for immediate therapeutic management,” Vander Heide said. “The results may also be applicable to a broader demographic experiencing severe COVID-19 disease. Management of these patients should include therapy to target these pathologic mechanisms.”