What autopsy reveals about coronaviruses

In dengue, a mosquito-borne tropical disease, she learned that the virus seems to destroy these platelet-producing cells, causing uncontrolled bleeding. The new coronavirus seems to have amplified its effect and caused dangerous coagulation.

“Covid-19 and dengue are really different, but the cells involved are similar.”

Autopsy has made great strides in understanding new diseases, from HIV/AIDS and Ebola to Lassa fever. The medical community expects the same for covid-19, a disease caused by the new coronavirus. Autopsy is becoming an important source for studying possible treatments, as vaccines are probably months ahead even in the most optimistic scenarios.

When the pandemic struck the United States in late March, many hospital systems were overwhelmed by life-saving efforts, spending too much time digging into the secrets of the dead. However, by the end of May and June, the first mass reports of deaths from patients aged 32 to 90 at half a dozen institutions were issued in a row. Research has identified some of our early disease premonitions and has been countered by others-and has opened up new mysteries about pathogens that have killed more than half a million people worldwide.

But the brain and heart brought surprises.

“It’s about what we are Absent See,” said Mary Fowkes, an associate professor of pathology, a member of Mount Sinai Health’s team who performed an autopsy on 67 covid-19 patients.

Extensive report about Neurological symptoms In relation to the coronavirus, she expected she would find the virus and/or inflammation in the brain. However, there were few. As for the heart, many doctors have warned for months of cardiac complications suspected of being myocarditis, inflammation of the myocardial wall, or stiffening, but researchers at autopsy find no evidence of the condition. I was surprised that I could not do it.

Another unexpected finding, according to pathologists, is that hypoxia and clot formation in the brain can begin early in the disease process. This can have a huge impact on how people with covid-19 are treated at home, even if they don’t have to be hospitalized.

Some critics say the new US outbreak was devastating in April, with premature mitigation of social distance restrictions, mainly in some states in the South and West. Because even the day is overtaking. New modeling studies estimate that about 22 percent of the population, or 1.7 billion people around the world, including 72 million in the United States, are prone to serious illness when infected with the virus. According to an analysis published this month at Lancet Global Health, about 4% of these people will need to be hospitalized — emphasizing bets as coroners continue to look for clues.

At best, autopsy can reconstruct the natural course of the disease, but the process of new, highly infectious diseases can be cumbersome and delicate. To protect the pathologist and prevent the virus from getting into the air, it is necessary to take organs with special tools and soak them in antiseptic solution for several weeks before investigating. Next, each organ needs to be cut and small pieces of tissue collected for study with different types of microscopes.

One of the first American surveys published on April 10th was from New Orleans. The patient was a 44-year-old man being treated at LSU Health. Richard Vander Heide remembers cutting the lungs and probably finding hundreds or even thousands of microclots.

“I will never forget that day,” recalled Vander Heide, who has been autopsy since 1994. “I told the resident, “This is a very rare thing.” I’ve never seen anything like this. “

But when he moved to the next patient and the next, Vanderheide saw the same pattern. He was very afraid, he said, as he shared the paper online before submitting it to the journal so doctors could immediately access the information. The findings have caused a turmoil in many hospitals and have affected some doctors to start giving anticoagulants to all covid-19 patients. That is common now. The final peer-reviewed version containing 10 patients was subsequently published Lancet May.

The same was true for other lung autopsies, such as those described in a paper of 38 Italian patients, a study of Mount Sinai Health in 25 patients, and a joint study of Harvard School of Medicine and 7 German researchers. Coagulation findings have been reported.

Recently, last month’s survey Lancet eClinical Medicine, Found that abnormal coagulation was found in the heart, kidneys, liver, and lungs of seven patients, which may be a major cause of multiple organ failure in covid-19 patients.

The next organ studied closely was the heart. One of the most dreadful early reports of the Chinese coronavirus was that a significant proportion (up to 20-30%) of hospitalized patients appeared to have myocarditis, which could lead to sudden death. In this condition, the muscles of the heart are thickened, which prevents efficient pumping.

According to pathologists, classic myocarditis is usually easy to identify at necropsy. It occurs when the body recognizes the tissue as foreign and attacks it. In that situation, the heart has a large dead zone, and muscle cells called muscle cells are surrounded by cells that fight infection, called lymphocytes. But in autopsy samples taken to date, dead muscle cells weren’t surrounded by lymphocytes, so the researchers scratched their heads.

Fowkes from Mount Sinai, and her colleague Claire Bliss, Published online Although not yet peer-reviewed, they said there was “very mild” inflammation of the heart’s surface, but it didn’t look like myocarditis.

NYU Langone’s Rapkiewicz, who studied seven hearts, was shocked by the abundance of rare cells called megakaryocytes in the heart. The cells that produce platelets that control coagulation are usually found only in the bone marrow and lungs. When she returned to lung samples from patients with coronavirus, she found that those cells were too numerous there.

“We couldn’t remember the incident before we saw it,” she said. “It was worth noting that they were in the heart.”

In April, Vander Heide of LSU reported the results of a preliminary study of 10 patients and published a more detailed paper including case studies under consideration in the journal. “When you look at your heart, you don’t know what you can’t see. You’ll expect it.”

He said several autopsied patients had cardiac arrest in the hospital, but when they were examined the major damage was to the heart, not the lungs.

Of all the symptoms of coronavirus, the brain effects are one of the most annoying. Many neurological disorders have been reported, including odor and taste deterioration, changes in mental status, stroke, seizures, and even delirium.

Chinese study published in BMJ’s Journal of Neurology, Neurosurgery & Psychiatry, In March, it was found that 22% of 113 patients experienced neurological problems ranging from excessive drowsiness to coma-the condition is usually grouped as a disturbance of consciousness. In June, a French researcher reported that 84% of patients receiving intensive care had neurological problems, and one-third were confused or confused at discharge. Also this month, British people found 57 of 125 coronavirus patients with new neurological or psychiatric diagnoses had a stroke due to a blood clot in the brain and 39 had altered mental status. Did.

Based on such data and anecdotal reports, Isaac Solomon, a neuropathologist at Brigham and Women’s Hospital in Boston, set out to systematically investigate where the virus was embedded in the brain. He performed 18 consecutive death autopsies and sliced ​​major areas: cerebral cortex (gray matter involved in information processing), thalamus (modulated sensory input), basal ganglia (responsible for motor control). There is) etc. Each was divided into a 3D grid. Ten sections were retrieved and surveyed from each.

He found fragments of the virus only in some areas, and when the patient died, it was unclear whether they were dead remnants or active viruses. There were only small pockets of inflammation. However, there was a large zone of damage due to lack of oxygen. Regardless of whether the deceased was a long-term intensive care patient or sudden death, Solomon said the pattern was creepy.

“We were very surprised,” he said.

When the brain does not get enough oxygen, individual neurons die, and the death is permanent. To some extent, people’s brains can make up for it, but at some point, the damage is so great that various functions begin to decline.

According to Solomon, at a practical level, if the virus doesn’t get into the brain in large numbers, for example in some patients with West Nile and HIV, it becomes more difficult to treat once the infection is widespread, which makes it more of a drug development. Useful Another point, the findings highlight the importance of supplementing people with oxygen to prevent irreversible damage.

Solomon whose work was published as a letter on June 12 New England Medical JournalAccording to the results of the survey, the damage has been occurring for a long time, and people are wondering about the effects of the virus on people who are less ill. “The big and lasting problem is what happens to eager survivors,” he said. “Are there any lasting effects on the brain?”

The team at Mount Sinai Health, which has taken tissue findings from 20 brains, was also confused at not finding a lot of viruses and inflammation. However, the group noted that the widespread presence of small blood clots on the paper was “prominent.”

“If you have a single blood clot in your brain, you will always see it. But what we see is that some patients have multiple strokes in blood vessels in two or three different areas. Is there,” Fowkes said.

Lapkievich said it was too early to see if the latest batch of autopsy results could translate into treatment changes, but this information paved the way for further exploration. One of her first calls after being aware of abnormal platelet-producing cells was to Jeffrey Berger, a cardiologist at New York University who runs a funded lab at the National Institutes of Health focused on platelets. It was a phone call.

According to Berger, autopsy suggests that anticoagulants, in addition to anticoagulants, may help reduce the effects of covid-19. He is also leading a major clinical trial investigating the optimal dose of anticoagulant to address the issue.

“This is just one part of a very large puzzle and there’s a lot to learn,” he said. “But if we can prevent serious complications and more patients to survive the infection, it will change everything.”