Rapkiewicz directs autopsies at NYU Langone Health, and when she was taking on the grim and daunting tasks she noticed some organs had far too many of a special cell that is rarely found in the places where it was. Though she had never seen it before it seemed familiar, and after researching history books she found reference to a 1960s report on a patient with dengue fever.
Rapkiewicz learned that in dengue the virus appeared to destroy these cells which produces platelets and leads to uncontrolled bleeding, and this novel virus seems to be amplifying their effects to cause dangerous clotting. Of the parallels she says: “Covid-19 and dengue sound really different, but the cells that are involved are similar.”
Autopsies have been used as a valuable source of information and breakthroughs leading to understanding new diseases for many decades, with this outbreak the medical community is counting on them to do the same for COVID-19. Hospital systems are too busy trying to save lives to spend too much time trying to reveal the secrets of the dead, but the first large batch of reports involving patients ranging between the ages of 32-90 have been published. Investigations have confirmed early suggestions of the disease and refuted others, but they have also opened up new mysteries about this pathogen.
Consistent across several studies is the finding that this virus appears to attack the lungs most viciously, and the pathogen was also found in parts of the brain, liver, kidneys, spleen, gastrointestinal tract, and in the endothelial cells that line blood vessels. Also as was suspected there was widespread clotting found in many organs. But the brain and heart revealed surprising findings.
“It’s about what we are not seeing,” said Mary Fowkes, an associate professor of pathology who is part of a team at Mount Sinai Health that has performed autopsies on 67 COVID-19 patients.
Fowkes was expecting to find the virus or inflammation or both in the brain given the reports about neurological symptoms related to this virus, but there was very little and all autopsy investigations found no evidence of myocarditis in the heart despite months of concern over suspected cardiac complications.
Pathologists found another unexpected finding, that of the oxygen deprivation of the brain and the formation of blood clots may start early on in the disease process; this could have implications for how those with this disease are treated and home and if they need to be hospitalized.
Autopsies can help to reconstruct the natural course of disease, but the process for such a new and highly infectious disease requires dedicated and meticulous work with the use of specialized tools to harvest organs to be put into a disinfecting solutions for several weeks before they can be studied to avoid sending the virus into the air. After this process each organ must be sectioned and small bits of tissue must be collected to study under different types of microscopes.
One of the first American investigations to be made public was that of a 44 year old man who was treated in LSU Health; Richard Vander Heide who has been performing autopsies since 1994 remembers discovering what was probably hundreds or thousands of microclots in the lungs. This was something that was unusual that he has never seen before, but as he moved to the next patient and the next he saw the same pattern. He was so shocked and alarmed that he shared a paper online before submitting to a journal to get this information out immediately to all doctors; and his findings have influenced many hospitals to give blood thinners to some COVID-19 patients, and it is now a common practice. Subsequently the final peer reviewed version has been published in the Lancet.
Other autopsies have reported similar findings of clotting, and more recently a study published in the Lancet’s eClinical Medicine reports abnormal clotting in the heart, kidney, liver, and lungs leading the authors to suggest that this may be a cause of the multiple organ failure in COVID-19 patients.
One of the frightening early reports was the number of hospitalized patients appearing to have myocarditis that could lead to sudden death. Classic myocarditis is typically easy to identify in autopsies, as it occurs when the body perceives tissues to be foreign and attacks it causing large dead zones in the heart, and muscle cells would be surrounded by infection fighting lymphocytes cells. However thus far in the autopsy samples taken the dead myocytes were not surrounded by lymphocytes, only very mild inflammation has been seen on the surface of the heart but nothing that looks like myocarditis, according to Fowkes from Mount Sinai.
Rapkiewicz of NYU Langone was shocked at the abundance in the heart of the rare megakaryocytes cells, these cells produce platelets that control clotting, and typically exist only in bone marrow and lungs. Taking samples from COVID-19 patients lungs she discovered that those cells were in abundance there as well. “I could not remember a case before where we saw that,” she said. “It was remarkable they were in the heart.”
From LSU Vander Heide has a more in-depth paper that is under review in a journal explains that “when you look at a covid heart, you don’t see what you’d expect.” According to him a few autopsies he performed were on patients that had gone into cardiac arrest in the hospital, but after examination the primary damage was found in the lungs not in the heart.
A host of neurological impairments are also being reported including excessive sleepiness, reduced ability to smell or taste, altered mental status stroke, seizures, and delirium. 84% of patients in France in ICUs are reported to have had neurological problems with one third being confused or disoriented at discharge. In the UK one report suggests that 57 of 126 patients with a new neurological or psychiatric diagnosis experienced a stroke due to a blood clot in the brain, with 39 having an altered mental state.
Isaac Solomon, a neuropathologist at Brigham and Women’s Hospital in Boston has conducted autopsies taking slices of key areas of the cerebral cortex, thalamus, basal ganglia, and others to investigate where this virus may be embedding itself into the brain. Each slice is divided into three dimensional grids, and 10 sections were taken from each to be studied. Solomon was only able to find snippets of the virus in some areas, and it was unclear whether they were dead remnants or active virus when the patient died; only small pockets of inflammation were found, but large swaths of damage due to oxygen deprivation was found. According to Solomon the pattern was eerily similar regardless of the patient suddenly dying or being in long term intensive care.
Findings underscore the importance of getting supplementary oxygen to patients quickly to prevent irreversible damage. Solomon has published a report in the New England Journal of Medicine, in it he suggests the findings suggest that the damage had been happening over a longer period of time, making him wonder about the effect on those who had been less ill.
“The big lingering question is what happens to people who survive covid,” said Solomon. “Is there a lingering effect on the brain?”
A Mount Sinai Health team took samples from brains, who were also shocked at the lack of virus and inflammation discovered, but they noted the widespread presence of tiny clots as being striking.
“If you have one blood clot in the brain, we see that all the time. But what we’re seeing is, some patients are having multiple strokes in blood vessels that are in two or even three different territories,” Fowkes said.
Rapkiewicz believes that it is too early to know whether the newest batch of autopsy reports can be translated into changes in treatment, but the information has revealed new paths to explore. One of her first calls was to Jeffrey Berger who is a cardiac specialist at NYU and runs a NIH funded lab focusing on platelets after she noticed the unusual platelet producing cells.
According to Berger the autopsies suggest that antiplatelet medications along with blood thinners may be useful for some of the symptoms of COVID-19, and he is pivoting a clinical trial to investigate the optimal doses while examining the effectiveness of such treatment.
“It’s only one piece of a very big puzzle, and we have a lot more to learn,” said Berger. “But if we can prevent significant complications and if more patients can survive the infection, that changes everything.”
