Silent evidence: How does the new coronavirus "devour" the patient's body?

Two months ago, Fanpu published an article discussing the strange symptoms caused by COVID-19 infection, mentioning that although COVID-19 is considered a respiratory disease, it can cause many strange symptoms, such as stroke, thrombosis, hypoxia, "COVID-19 toes" shaped like frostbite, delirium and other strange brain diseases... While frontline doctors record patients' symptoms in detail, pathologists are working silently and nervously in the back. Several autopsy reports released in the past two months show that the most abnormal phenomenon in patients is thrombosis, not inflammation. This may partially explain the various strange symptoms previously observed in clinical practice, and also prove that New York doctors are right to use heparin (for anticoagulation) in large-scale treatment.

Text/ Xiaoye

As of today, there have been 11,669,259 confirmed cases of novel coronavirus pneumonia (COVID-19) worldwide, and 539,906 deaths. On the fierce front battlefield, there are still many medical staff around the world fighting on the front line, striving to save more lives.

In the quiet backstage, Amy Rapkiewicz, a pathologist at NYU Langone Health, calmly opened the body of a COVID-19 patient in front of her and carefully removed key organs such as the heart and lungs using special tools. Next, these organs need to be soaked in a disinfectant solution for several weeks, then removed and cut, and small pieces of tissue samples are selected and placed under a microscope for detailed analysis.

Although the virus prevents patients from ever speaking out about their suffering, experts like Lapchiewicz know how to work with "silent witnesses" whose bodies still remain in the world will tell us more groundbreaking clues, help us better understand the disease, and develop potential new treatments.

Since the outbreak of the COVID-19 pandemic, doctors have viewed COVID-19 as a standard respiratory disease, with the virus attacking not only the lungs but also the brain, kidneys, liver, gastrointestinal tract, and spleen. Since March this year, China, the United States, and European countries have successively published autopsy reports, unanimously confirming that the organ most violently attacked by the new coronavirus is the lungs - pathogens have been found in both lungs and vascular endothelial cells of deceased patients. But as we continue to investigate, the situation does not seem to be entirely as expected...

Lungs: Full of microthrombi Under the microscope, Lapkiewicz observed that the virus damage to the lung, kidney, and liver specimens was no different from what other doctors had reported. But then she saw something unexpected and familiar—microthrombi everywhere. After looking through historical materials, she suddenly remembered that this was dengue fever! !

Dengue fever is a tropical disease spread by mosquitoes. The virus "kidnaps" white blood cells, causing them to release signaling proteins such as interferon and cytokines, "relaxing" blood vessels, increasing vascular permeability, and causing uncontrollable bleeding in the body. She was extremely surprised: "COVID-19 and dengue fever sound unrelated, but the consequences of the disease are so similar!"

April 10 was the day when the first autopsy was performed in the United States. Richard Vander Heide of the Louisiana State University Health Sciences Center (LSU Health) in New Orleans clearly remembered his surprise when he cut open the lungs of the deceased and saw hundreds of microscopic blood clots inside:

"I will never forget this day. I have been performing autopsies since 1994 and I have never seen anything like this."

He then dissected the second body and saw the same thing happen to him, as did the third and fourth bodies. So, alerted, he immediately wrote an article and published a preprint online before submitting it, hoping to attract the attention of other doctors immediately.

The news quickly spread throughout American hospitals, and doctors began giving all patients blood thinners, which has now become a common practice. Vander Heide's paper on the autopsies of 10 patients was published in The Lancet in May after peer review. In his paper, he described in detail the important findings of the autopsies: thrombosis and microvascular disease in the small blood vessels and capillaries of the lungs, accompanied by bleeding. He clearly pointed out that these were the main causes of death. [1]

Subsequently, other similar lung anatomy studies, including a paper involving 38 autopsies by an Italian team, 25 autopsies by Mount Sinai Health, seven autopsies by Harvard Medical School and German researchers, and a study by Lapkiewicz's Langone Health team, all reported similar microthrombi.

Lapkiewicz published her autopsy results in The Lancet in June. In the seven patients she dissected, she found abnormal thrombotic symptoms not only in the lungs but also in the heart, kidneys, and liver. She also emphasized that thrombosis was a common and prominent feature of multiple organs, and that platelet-rich megakaryocytes indicated thrombosis (Figure 1), which began to play a destructive role in the early stages of the disease. [2]

Figure 1. Megakaryocytes in the heart, kidney, lung, and bone marrow [2]

Megakaryocytes are a type of bone marrow cell responsible for producing blood clotting cells (platelets), which are necessary for the formation of normal blood clots. Normally, one in ten thousand bone marrow cells is a megakaryocyte, but during certain diseases, this number can increase nearly tenfold. Each megakaryocyte can produce approximately 2,000 to 7,000 platelets. (Source: wikipedia)

Heart: Is it myocarditis? In March of this year, some reports indicated that patients with COVID-19 may experience symptoms of myocarditis, and several early studies on COVID-19 patients in China also showed that 20% to 30% of hospitalized patients had myocardial damage. [3, 4] Myocarditis can cause myocardial thickening, ultimately leading to heart dysfunction, arrhythmias, and the risk of death. However, these reports did not include analysis of the pathological characteristics of myocardial tissue.

Typically, myocarditis is easily identified during an autopsy. Inflammation occurs when the body senses a tissue as foreign and begins to attack it. The heart's myocardial cells are surrounded and killed by lymphocytes that specialize in fighting infection, so the hearts of people with myocarditis should have large areas of dead myocardial cells.

However, "we didn't see that," said Mary Fowkes, assistant professor of pathology at Mount Sinai Health Center. Fowkes, who has extensive experience, has performed autopsies on 67 COVID-19 patients, and Clare Bryce, who is on the same team as her, has studied 25 of the hearts for this purpose. The two published a preprint paper online, saying that they saw some "very mild" inflammatory lesions on the surface of the heart, but they did not look like myocarditis at all. [5]

Lapkiewicz saw a large number of megakaryocytes in the seven hearts she dissected. Megakaryocytes should exist in the bone marrow and in small numbers, but now they are all over the heart, which shocked her.

“If you examine the heart of a COVID-19 patient, you might not see what you expect (myocarditis),” says van der Heide, who has a more in-depth paper under review. Several of the bodies he has dissected died of cardiac arrest, but the autopsies showed that the majority of the damage was in the lungs, not the heart.

Brain: Neural network virus damages brain nerves? In the past, patients with COVID-19 have reported loss of smell or taste, changes in mental state, and even various neurological disorders such as epilepsy and mental confusion. In April of this year, an early report published in the journal Neurology, Neurosurgery and Psychiatry mentioned symptoms related to intracranial infection in patients with COVID-19, such as headaches, epilepsy and impaired consciousness. [6] In June, French researchers reported that 84% of intensive care patients had neurological problems, and one-third of patients were not in a good mental state when they were discharged from the hospital. In the same month, British researchers found that 57 of the 125 confirmed patients had suffered a stroke due to blood clots in the brain, and 39 had changes in mental state (i.e. various brain dysfunction diseases, with mild symptoms of confusion and severe symptoms of coma). [7]

Faced with the above data and reports that sounded strange, Isaac Solomon, a neuropathologist at Brigham and Women's Hospital in Boston, decided to systematically investigate which brain regions the virus might be hiding in. He dissected the bodies of 18 patients who died of COVID-19 one after another and sliced ​​key brain regions: the cerebral cortex, thalamus (regulating sensory input), basal ganglia (responsible for motor control), etc. Each slice was divided into a three-dimensional grid, and 10 cross sections were carefully analyzed.

The results surprised him. The virus fragments only appeared in individual areas, and it was unclear whether the viruses were dead or still active when the patient died. Moreover, only a small number of areas showed inflammation, and large-scale damage was caused by brain hypoxia. Brain hypoxia causes nerve cells to die, and no new nerve cells are produced after death. Although the human brain has certain compensatory functions, when the range of hypoxia is too large, various brain functions still begin to degenerate. This is the case for patients who have been in intensive care units for a long time or patients who die suddenly.

The good news, however, is that if the virus does not enter the brain in large numbers, it could help with drug development, Solomon said, and the finding highlights the need to give patients oxygen in a timely manner to prevent irreversible brain damage. His study was published in the New England Journal of Medicine on June 12. [8]

The Mount Sinai team's brain autopsies confirmed Solomon's claims, and they did not find large numbers of viruses or inflammatory lesions in the brain. However, they noticed something similar to what Lapkiewicz had seen: microscopic blood clots were widespread in the brain. Fox added: "In some patients, they had multiple blood clots in blood vessels in two or three different areas of the brain."

This silent battle with the virus has made scientists dare not relax at all. Although the latest anatomical discoveries are still few in number, whether they can be transformed into practical treatment ideas is still inconclusive. However, the best autopsy can help scientists reconstruct the natural occurrence of the disease, and the new information provided by the autopsy is likely to open up a new path for virus exploration.

Jeffrey Berger, a cardiologist at New York University, commented after learning of Lapkiewicz's findings that the autopsy showed that in addition to blood thinners, antiplatelet drugs may also be effective in treating COVID-19. "We still know very little about the new coronavirus, but each study is a small piece of the puzzle to complete this huge virus. In addition, if we can prevent the occurrence of serious complications, we can save more lives and ultimately completely change the course of the epidemic."

References

[1] https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30243-5/fulltext

[2] https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30178-4/fulltext

[3] https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30178-4/fulltext

[4] https://jamanetwork.com/journals/jamacardiology/fullarticle/2763845

[5] https://jamanetwork.com/journals/jamacardiology/fullarticle/2763845

https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524

[6]https://jamanetwork.com/journals/jamacardiology/fullarticle/2763845

[7] https://jamanetwork.com/journals/jamacardiology/fullarticle/2763524

[8]https://www.medrxiv.org/content/10.1101/2020.05.18.20099960v1

Compiled from: https://www.washingtonpost.com/health/2020/07/01/coronavirus-autopsies-findings/