Coronavirus autopsies: A story of 38 brains, 87 lungs and 42 hearts

What we’ve learned from the dead that could help the living.

The Washington Post, by Ariana Eunjung Cha, July 1, 2020
An examination room in the morgue at the Franklin County Forensic Science Lab in Columbus, Ohio. (Ty Wright/The Washington Post)

When pathologist Amy Rapkiewicz began the grim process of opening up the coronavirus dead to learn how their bodies went awry, she found damage to the lungs, kidneys and liver consistent with what doctors had reported for months.

But something was off.

Rapkiewicz, who directs autopsies at NYU Langone Health, noticed that some organs had far too many of a special type of cell rarely found in those places. She had never seen that before, yet it seemed vaguely familiar. She raced to her history books and — in a eureka moment — found a reference to 1960′s report on a patient with dengue fever.

In dengue, a mosquito-borne tropical disease, she learned, the virus appeared to destroy these cells, which produce platelets, leading to uncontrolled bleeding. The novel coronavirus seemed to amplify their effect, causing dangerous clotting.

She was struck by the parallels: “Covid-19 and dengue sound really different, but the cells that are involved are similar.”

Autopsies have long been a source of breakthroughs in understanding new diseases, from HIV/AIDS and Ebola, to Lassa fever — and the medical community is counting on them to do the same for covid-19, the disease caused by coronavirus. With a vaccine likely many months away, autopsies are becoming a critical source of information for research into possible treatments.

When the pandemic hit the United States in late March, many hospital systems were too overwhelmed trying to save lives to spend too much time delving into the secrets of the dead. But by late May and June, the first large batch of reports — from patients who died at a half-dozen different institutions — were published in quick succession. The investigations have confirmed some of our early hunches of the disease, refuted others — and opened up new mysteries about the novel pathogen that has killed more than 500,000 people worldwide.

Among the most important findings, consistent across several studies, is confirmation the virus appears to attack the lungs the most ferociously. They also found the pathogen in parts of the brain, kidneys, liver, gastrointestinal tract, spleen and in the endothelial cells that line blood vessels, as some had previously suspected. Researchers also found widespread clotting in many organs.

But the brain and heart yielded surprises.

“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.

Aerial view showing new graves in the Nossa Senhora Aparecida cemetery in Manaus, Brazil. (Michael Dantas/AFP via Getty Images)
Aerial view showing new graves in the Nossa Senhora Aparecida cemetery in Manaus, Brazil. (Michael Dantas/AFP via Getty Images)

Given widespread reports about neurological symptoms related to the coronavirus, Fowkes said, she expected to find virus or inflammation — or both — in the brain. But there was very little. When it comes to the heart, many physicians warned for months about a cardiac complication they suspected was myocarditis, an inflammation or hardening of the heart muscle walls — but autopsy investigators were stunned that they could find no evidence of the condition.

Another unexpected finding, pathologists said, is that oxygen deprivation of the brain and the formation of blood clots may start early in the disease process. That could have major implications for how people with covid-19 are treated at home, even if they never need to be hospitalized.

The early findings come as new U.S. infections have overtaken even the catastrophic days of April, amid what some critics say is a premature easing of social distancing restrictions in some states mainly in the South and West. A new modeling study has estimated that about 22 percent of the population — or 1.7 billion people worldwide, including 72 million in the United States — may be vulnerable to severe illness if infected with covid-19. According to the analysis published this month in the Lancet Global Health, about 349 million, or four percent of those people would require hospitalization — underscoring the stakes as autopsy investigators continue their hunt for clues.

Microclots in lungs

A health care worker in full protective gear examines the chest X-ray of a patient in a ward reserved for covid-19 patients at Hospital Juarez in Mexico City. (Eduardo Verdugo/AP)
A health care worker in full protective gear examines the chest X-ray of a patient in a ward reserved for covid-19 patients at Hospital Juarez in Mexico City. (Eduardo Verdugo/AP)

At their best, autopsies can reconstruct the natural course of the disease but the process for a new and highly infectious-disease is tedious and requires meticulous work. To protect pathologists and avoid sending virus into the air, they must use special tools to harvest organs and then dunk them in a disinfecting solution for several weeks before they are studied. They must then section each organ and collect small bits of tissue for study under different types of microscopes.

One of the first American investigations to be made public, on April 10, was out of New Orleans. The patient was a 44-year-old male who had been treated at LSU Health. Richard Vander Heide remembers cutting the lung and discovering what was likely hundreds or thousands of microclots.

“I will never forget the day,” recalled Vander Heide, who has been performing autopsies since 1994. “I said to the resident, ‘This is very unusual.’ I had never seen something like this.”

But as he moved onto the next patient and the next, Vander Heide saw the same pattern. He was so alarmed, he said, that he shared the paper online before submitting it to a journal so the information could be used immediately by doctors. The findings caused a stir at many hospitals and influenced some doctors to start giving blood thinners to all covid-19 patients. It is now common practice. The final, peer-reviewed version involving 10 patients was subsequently published in the Lancet in May.

Other lung autopsies — including those described in papers from Italy of 38 patients, a Mount Sinai Health study on 25 patients, a collaboration between Harvard Medical School and German researchers on seven and an NYU Langone Health on seven — have reported similar findings of clotting.

Most recently, a study out this month in the Lancet’s eClinicalMedicine, found abnormal clotting in the heart, kidney, liver, as well as the lungs of seven patients, leading the authors to suggest this may be a major cause of the multiple-organ failure in covid-19 patients.

Heart cells

The next organ studied up close was the heart. One of the most frightening early reports about the coronavirus from China was that a significant percent of hospitalized patients — up to 20 to 30 percent — appeared to have a heart issue known as myocarditis that could lead to sudden death. It involves the thickening of the muscle of the heart so that it can no longer pump efficiently.

Classic myocarditis is typically easy to identify in autopsies, pathologists say. The condition occurs when the body perceives the tissue to be foreign and attacks it. In that situation, there would be large dead zones in the heart, and the muscle cells known as myocytes would be surrounded by infection-fighting cells known as lymphocytes. But in the autopsy samples taken so far the dead myocytes were not surrounded by lymphocytes — leaving researchers scratching their heads.

Fowkes from Mount Sinai and her colleague, Clare Bryce, whose work on 25 hearts has been published online but not yet peer reviewed, said they saw some “very mild” inflammation of the surface of the heart but nothing that looked like myocarditis.

NYU Langone’s Rapkiewicz, who studied seven hearts, was struck by the abundance of a rare cell called megakaryocytes in the heart. Megakaryocytes, which produce platelets that control clotting, typically exist only in the bone marrow and lungs. When she went back to the lung samples from the coronavirus patients, she discovered those cells were too plentiful there, too.

“I could not remember a case before where we saw that,” she said. “It was remarkable they were in the heart.”

Vander Heide from LSU, who reported preliminary findings on 10 patients in April and has a more in-depth paper with more case studies on the topic under review at a journal, explained that “when you look at a covid heart, you don’t see what you’d expect.”

He said a couple of patients he performed autopsies on had gone into cardiac arrest in the hospital, but when he examined them, the primary damage was in the lungs — not the heart.

Brain grid

New graves are seen at dusk at a Muslim burial area provided by the government for victims of the coronavirus disease at Tegal Alur cemetery complex in Jakarta, Indonesia on June 27, 2020. (Willy Kurniawan/Reuters)
New graves are seen at dusk at a Muslim burial area provided by the government for victims of the coronavirus disease at Tegal Alur cemetery complex in Jakarta, Indonesia on June 27, 2020. (Willy Kurniawan/Reuters)

Of all the novel coronaviruses’s manifestations, its impact on the brain has been among the most vexing. Patients have reported a host of neurological impairments including reduced ability to smell or taste, altered mental status, stroke, seizures — even delirium.

An early study from China, published in the BMJ, formerly the British Medical Journal, in March, found 22 percent of the 113 patients had experienced neurological issues ranging from excessive sleepiness to coma — conditions typically grouped together as disorders of consciousness. In June, researchers in France reported that 84 percent of patients in intensive care had neurological issues, and a third were confused or disoriented at discharge. Also this month, those in the United Kingdom found that 57 of 125 coronavirus patients with a new neurological or psychiatric diagnosis had had a stroke due to a blood clot in the brain, and 39 had an altered mental state.

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 might be embedding itself in the brain. He conducted autopsies of 18 consecutive deaths, taking slices of key areas: the cerebral cortex (the gray matter responsible for information processing), thalamus (modulates sensory inputs), basal ganglia (responsible for motor control) and others. Each was divided into a three-dimensional grid. Ten sections were taken from each and studied.

He found snippets of virus in only some areas, and it was unclear whether they were dead remnants, or active virus when the patient died. There were only small pockets of inflammation. But there were large swaths of damage due to oxygen deprivation. Whether the deceased were longtime intensive care patients, or people who died suddenly, Solomon said, the pattern was eerily similar.

“We were very surprised,” he said.

When the brain does not get enough oxygen, individual neurons die and that death is permanent. To a certain extent, people’s brains can compensate but at some point, the damage is so extensive that different functions start to degrade.

On a practical level, Solomon said that if the virus is not getting into the brain in large amounts, that helps with drug development because treatment becomes trickier when it is pervasive, for instance, in some patients with West Nile or HIV. Another takeaway is that the findings underscore the importance of getting people on supplementary oxygen quickly to prevent irreversible damage.

Solomon, whose work was published as a June 12 letter in the New England Journal of Medicine, said the findings suggest the damage had been happening over a longer period of time, which make him wonder about the virus’s effect on people who are less ill. “The big lingering question is what happens to people who survive covid, he said. “Is there a lingering effect on the brain?”

Jan Claire Dorado, 30, and a physician, tends to a patient in an emergency room designated for coronavirus patients in Manila. (Eloisa Lopez/Reuters)
Jan Claire Dorado, 30, and a physician, tends to a patient in an emergency room designated for coronavirus patients in Manila. (Eloisa Lopez/Reuters)

The team from Mount Sinai Health, which took tissue findings from 20 brains, was also perplexed not to find a lot of virus or inflammation. However, the group noted in a paper that the widespread presence of tiny clots was “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 said it is too early to know whether the newest batch of autopsy findings can be translated into treatment changes, but the information has opened new avenues to explore. One of her first calls after noticing the unusual platelet-producing cells was to Jeffrey Berger, a cardiac specialist at NYU who runs a National Institutes of Health-funded lab that focuses on platelets.

Berger said the autopsies suggest anti-platelet medications, in addition to blood thinners, may be helpful to stem the effects of covid-19. He has pivoted a major clinical trial looking at optimal doses of anticoagulants to look at that question as well.

“It’s only one piece of a very big puzzle, and we have a lot more to learn,” he said. “But if we can prevent significant complications and if more patients can survive the infection, that changes everything.”

Read more:

California to no longer fund new testing sites, may close underutilized test sites

[Significant quote: “A Newsom administration official confirmed that the state wants to see counties fill at least 80% of testing slots at each location. And if testing drops below 50% for a few days or longer, counties are warned, the sites could be transferred elsewhere.”]

As coronavirus cases surge, California pauses multimillion-dollar testing expansion

Los Angeles Times, by Angela Hart, Rachel Bluth, July 1, 2020
Carson Mayor Albert Robles does self-testing outside the Congresswoman Juanita Millender-McDonald Community Center.
Carson Mayor Albert Robles self-tests for COVID-19 at a new drive-up site outside the Congresswoman Juanita Millender-McDonald Community Center. (Genaro Molina / Los Angeles Times)

SACRAMENTO —  In April, Gov. Gavin Newsom launched a multimillion-dollar state initiative to bring COVID-19 testing to the people and places with the least access: rural towns and disadvantaged inner-city neighborhoods.

California is now halting its expansion, citing costs, even as the state is getting walloped by record-setting spikes in new infections and double-digit increases in hospitalizations.

The state will no longer fund new testing sites, despite pleas from counties for additional assistance — and it has closed some locations and moved them elsewhere. It also has threatened to pull testing out of underutilized sites, according to nearly two dozen interviews with county public health officials.

While it’s early in the process, some winners and losers have emerged: El Dorado County, east of Sacramento, lost its testing site in the town of Shingle Springs in June because it couldn’t fill enough appointment slots, while Fresno County gained a site that had been pulled from elsewhere, said its health officer, Dr. Rais Vohra.

Yet San Mateo County has asked state officials three times for a second state-funded venue to address testing gaps in Black and farmworker neighborhoods but has been “told no, repeatedly,” said Justin Mates, deputy county manager. So the county transformed its sole state site into a roving testing unit.

“Equity is certainly a concern for us,” Mates said. “We really need help with testing access if we’re going to reach our Latino residents and places like East Palo Alto,” a diverse city whose population is mainly Latino, African American and Asian/Pacific Islander.

California has committed up to $132 million in contracts with two private COVID-19 testing companies, Verily Life Sciences and OptumServe, to offer free coronavirus tests at more than 100 sites that the Newsom administration has identified as “testing deserts.” The expansion has dramatically increased the state’s overall testing numbers, which swelled from 16,000 tests per day in April to 105,000 on Monday.

Testing is also available at county-funded locations, private pharmacies, hospitals and community clinics.

State Health and Human Services Secretary Mark Ghaly confirmed that California is pulling sites out of counties that aren’t generating high enough numbers and cutting off funding for new locations.

“With every asset and resource — especially when it’s scarce — you want it to go to places where it’s most needed,” Ghaly said. “It wouldn’t be prudent or wise to maintain spending in a place where resources aren’t being used.”

Newsom has voiced concern about the testing price tag, given “unprecedented” budget shortfalls. “There is a big cost associated with testing,” he said in late June.

A Newsom administration official confirmed that the state wants to see counties fill at least 80% of testing slots at each location. And if testing drops below 50% for a few days or longer, counties are warned, the sites could be transferred elsewhere.

Counties argue that there’s a public health benefit to keeping underperforming locations open — simply to ensure that testing is available to rural and disenfranchised communities. Across the state, counties are fighting to save state-funded sites even as they are being overwhelmed by increased numbers of COVID-19 cases, linked largely to social gatherings.

“It’s how we are able to quickly identify where the virus is and if there are hot spots,” said Dr. Olivia Kasirye, health officer for Sacramento County, where holiday celebrations and booze-fueled gatherings among family and friends are sending infection rates soaring.

Contra Costa County saw its testing numbers drop in June and was at risk of losing a state-funded site until it proved it could keep appointments near 80% of capacity, said its health officer, Dr. Chris Farnitano.

Riverside County was warned June 16 that a state-funded site north of Temecula would be “moved to another county” if it didn’t get its testing above 50%, according to an email from the state’s testing task force. The state told Mendocino County it could lose its state-funded site, the only free testing available within a two-hour drive for some rural residents, if it didn’t push numbers up.

Alameda County grew so frustrated with state requirements that it undertook a testing expansion of its own.

“We realized we couldn’t depend on the state, especially to reach our vulnerable communities,” said Dr. Jocelyn Freeman-Garrick, an emergency room physician at Highland Hospital in Oakland, who is leading the county’s testing task force.

El Dorado County, which lost its site, so far has maintained a relatively low count of COVID-19 cases. It can’t afford to replace the site but will “make do,” said county spokesperson Carla Hass.

Ghaly said the state is working with counties in danger of losing sites to give them a chance to fill testing slots. State officials declined to say how many counties have lost sites, but as new infections have soared, testing numbers are starting to pick back up. The list of counties at risk of losing a site has dwindled from around a dozen in early June to a few last week.

Public health experts say focusing so intently on testing numbers, and not on adequate testing in Black and Latino neighborhoods, risks abandoning communities that already face immense barriers to healthcare.

“If you ignore these communities, then we’ll keep seeing the kinds of surges that we’re seeing now,” said Dr. Tony Iton, formerly the top health official for Alameda County and now a senior vice president of the California Endowment, which is working with counties to expand testing in underserved neighborhoods.

Entrenched socioeconomic barriers also make it difficult to get, and keep, testing numbers up. For instance, people who want to be tested at state sites often need Internet access and an email address. Most sites are drive-through, requiring access to a vehicle.

Many low-income people can’t meet those requirements, while undocumented immigrants fear that providing personal information to obtain a test could expose them to immigration officials, said Dr. Marty Fenstersheib, a former health officer of Santa Clara County who is leading its testing program.

“We can have all the tests we want, but if people are afraid to come and get tested, it’s not going to be of any benefit,” he said.

State contracts that fund the testing sites were extended in June but are set to expire Aug. 31, and administration officials have not told counties whether the state will continue funding them after that, said Mimi Hall, president of the County Health Executives Assn. of California and director of public health for Santa Cruz County.

Counties can’t afford to keep the sites running, said Hall, who is on the state’s testing task force.

“It’s hard to plan when we don’t know how long we’ll be able to keep them,” Hall said.

This story was produced by KHN (Kaiser Health News), which publishes California Healthline, an editorially independent service of the California Health Care Foundation. KHN is not affiliated with Kaiser Permanente.