Most research into COVID-19 coronavirus is focused on what it is and how to stop it. Virtually all of that research was on live subjects. Now, a team at The Mount Sinai Hospital is looking at the dead to help them better understand COVID-19’s broad impact on the human body.
Sometimes the best way to understand how a pathogen impacts the living is to study the dead. That’s what a pathology team from The Mount Sinai Hospital believes, at least. They’re working on the broadest and most comprehensive autopsy analysis yet done on COVID-19 victims. Their hospital was a key location relative to the global pandemic. Their work is revealing some fascinating and complex new realities about the virus.
“An essential contribution of pathology is the understanding of the biology of the disease and the range of organ damage, and for this reason, we decided to uncompromisingly perform as many autopsies as possible,” said Carlos Cordon-Cardo, MD, Ph.D., Irene Heinz Given and John LaPorte Given Professor and Chair of the Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Molecular and Cell-Based Medicine, and co-author of the study.
Why autopsies? Autopsies allow pathologists to examine tissue, organs and organ systems in ways not possible in a living human being.
“Post-mortem examinations (autopsies) are the gold standard for the elucidation of the underlying pathophysiology of disease. Despite a rapidly growing body of literature focusing on the clinical impact and molecular microbiology of SARS-CoV-2, autopsy studies have comparatively been few and far between,” said Mary Fowkes, MD, Ph.D., Director of the Autopsy Service, and senior author of the paper. SARS-CoV-2 is the virus that causes COVID-19.
Their analysis was released on the pre-print server MedRxiv. It includes analysis of the first 67 of more than 90 autopsies already done by the team. They combined the lab data, clinical history and the gross anatomical findings from autopsy for each patient. They were able to perform microscopic examinations using immunochemistry, molecular pathology assays, electron microscopy and special stains.
Since the start of the original outbreak in the city of Wuhan and Hubei Province in China, COVID-19 has been considered primarily a respiratory illness. But the Mount Sinai team found some other, more surprising impacts of the virus.
They show in detail that COVID-19 also causes damage to the endothelium, a thin layer of cells that line blood vessels, in patients who died of the virus. This seems to explain the hypoxia and clotting abnormalities which were observed in severely and critically ill patients. This is also connected to the multi-organ failure that was the immediate cause of death for some patients.
“The physical evidence we ascertained through our postmortem analyses helps elucidate the mechanisms behind some of the clinical symptoms observed by physicians treating COVID-19 patients, including thromboembolisms and neuropsychiatric disorders,” says Clare Bryce, MBChB, Associate Professor of Pathology, Molecular and Cell Based Medicine, and, first author of the study.
Diffuse damage to the alveoli, the small sacs where the blood exchange of oxygen and carbon dioxide happens, was present in virtually all cases. In cases of clinical acute respiratory distress syndrome ARDS,) this is commonly found. Most of the analyses also found fibrin, which is a fibrous, non-globular protein that’s part of the clotting of blood, and/or platelet thrombi, or clots, to some extent.
This same pathology is common to a number of coronaviruses. The difference with this one is the totality of findings across the entire autopsy group. Blood clots in other organ systems, including the liver, kidney and brain indicate endothelial damage as an underlying contributor. The team connected this to the coagulation cascade and consistent elevation of inflammation markers in the blood.
Only a few of the brains examined showed inflammation. While only a few revealed small foci of chronic inflammation, researchers were surprised at another finding in a significant number of cases. They found microthrombi, along with small, patchy areas of tissue death related to blockage of blood vessels in multiple areas of the brain. They believe these may explain some of the psychological changes noted in some COVID-19 sufferers.
A better understanding of the pathophysiology of COVID-19 seems to provide a solid pretext for the use of some novel treatments for the virus. Among these is the anti-coagulation strategies being used by some clinical leaders. These include Mount Sinai’s own Valentin Fuster, MD, Ph.D., who is the director of Mount Sinai Heart and Physician-in-Chief at The Mount Sinai Hospital.
While most researchers seem focused on the living – living patients, live virus and living tissue – a look at the dead seems to be revealing some unexpected results. It’s also teaching us some things about the virus that we may not have expected.
In the fight against this novel coronavirus, however, more data and more knowledge certainly seem to translate to more power and more weapons.
Keep the faith and keep after it!
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Journal Reference – Clare Bryce et al. 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, (2020). DOI: 10.1101/2020.05.18.20099960