A pathologist’s look inside coronavirus disease
The pathologist snaps a tissue sample under a microscope.
From the palette of samples, including heart, spleen, kidney, trachea, liver, he’s chosen the lung for this demonstration. All of it comes from an elderly male who died of COVID-19, one of Ontario’s first pandemic victims.
It’s a tiny piece of tissue, smaller than a pinkie nail. Shades of pink, mostly, with filaments of red and pinpricks of black.
The white circles are gossamer-like air sacs. Between them, the lungs have somewhere in the neighbourhood of six hundred million alveoli. Oxygen travels through bronchial tubes through the spongy part of the lung — millions of alveoli — penetrating their walls.
“That’s oxygenation,” explains Dr. Michael Pollanen. “That’s how the world works. Amazing huh?”
There’s evidence of inhaled dust, too. And the black pattern of dots? “Glad you asked. Oh boy, you’re not going to like the answer! What’s black in your lung? Smoking. This is what we call carbon pigment and it’s present in all city dwellers, more so in smokers. If this man lived in the country, you wouldn’t see it. But he lived in the city.”
Noting some of the larger alveoli, Pollanen says: “This is emphysema. That’s actually smoking-related lung disease. The lungs here are not entirely normal. This is a bit of a clue. His lungs were susceptible because of this.”
Susceptible to the coronavirus, susceptible to the COVID-19 that killed him in a very short time.
Some of the air sacs, “you see there’s debris in them. And you see what looks like spiderwebs. These are inflammatory cells. They’re not supposed to be there.”
More clues for what brought about mortality. But the real culprit, the gist of the disease that killed both this man and more than 302,000 people globally, as of this writing, are the Type 2 pneumocytes in the lining of the alveoli.
“In normal lungs, they should not be as prominent as this. They are prominent here because this is the target of the virus: those cells, the pneumocytes. That’s where the SARSCoV-2 goes into and binds.”
Plastering the surface of the cell. The phenomenon that leads to acute respiratory distress syndrome: an inability to breathe, which, at its most severe manifestation, lands patients on ventilators. Twothirds of them will die anyway.
“This man has a whole bunch of them,” Pollanen says of the pneumocytes.
The spiky virus, with its crown of probes (hence the moniker coronavirus)that attach, like suction cups, hijacking the cell, can’t be seen in this slide. But they can be identified under a more powerful electron microscope in the microbiology lab.
“It’s inside the nucleus of the cell. They’re all proliferating and reactive. Then notice over here, these are inflammatory cells. So there’s the inflammation. What’s really interesting — you have to tune your eye to it — is the pink material here. I’m tracing now the wall of the alveolus … This pale pink stuff is more feathery. That is called a hyaline membrane. And this is a sign of severe lung damage.”
Many forms of serious lung damage will cause hyaline membrane. “You could have different viruses that cause the same appearance,” Pollanen points out. “That’s why you have to demonstrate the virus.”
He interrupts his non-linear dialogue, as scientist and reporter hunch over microscopes, to admire one particular wedge of the sample. “Ooh, look at that! Chunk of pink. That’s a really beautiful Type 2 right there.”
Beauty is in the eye of the scientific beholder.
For the reporter, Pollanen compresses the vast scientific concepts into a nut-graph: “Inside the alveoli, normally full of gas, we have what? Proliferating pneumocytes, inflammatory cells, hyaline membranes … You have solid material inside those microscopic air sacs. That’s why, in an X-ray of the lungs, they would look white, because the X-ray can’t penetrate it. Also, very importantly, oxygen gas has got to go into those alveoli and then get into the blood vessels. That’s very difficult when the alveoli are filling up with this material.”
It’s an extraordinary inside look, literally, at COVID-19.
The Star’s tour guide here at the coroner’s HQ on Morton Shulman Avenue, Dr. Pollanen, is not just any ordinary pathologist; he’s Ontario’s chief forensic pathologist. “The brains of it all,” extols Dr. Dirk Huyer, Ontario’s chief coroner, the medico-legal yin to Pollanen’s forensic yang. (The pathology part of the coroner’s system is the Ontario Forensic Pathology Service.)
“I spend a lot of time trying to understand real content. Forensic pathology gives you an amazing perspective on medicine, too. One minute, you’re dealing with the cellular processes of COVID-19 and, the next minute, you’re dealing with skeletal remains from a clandestine grave.” The men and women who respond to homicides and accidents and, when deemed necessary, open up the victims from stem to stern.
But while the path of a bullet in the head can be easily traced visually, disease, COVID-19 specifically, is another kettle of fish entirely.
The disease may show itself under a microscope, prove the virus was present, but that doesn’t necessarily mean it actually killed that person.
Could be an underlying condition. Could be a secondary condition.
That’s where “clinical pathological correlation” enters the picture — the observations of symptoms and manifestations from everyone who’s cared for the patient: lung specialists, nephrologists, cardiologists, neurologists, all the doctors and nurses.
“Then, you look at autopsy and you put it all together,” says Pollanen, with a voilà gesture.
He’s conducted far fewer autopsies on COVID-19 victims than you might imagine. Autopsies have been performed on only a small fraction of bodies and none, apparently, by pathologists working in hospital morgues. (Hospital pathologists do autopsies purely for medical reasons.)
Families don’t want their loved ones cut open and the coroner’s office is quite considerate of that. There are also risks, although the autopsies are done in self-containment rooms and those performing them wear protective equipment.
“When you’re thinking about potential pathogens, aerosolized in the autopsy room, we will take a minimally invasive approach for health and safety considerations,” Pollanen notes. “Because we have to balance what we need to know versus the health and safety of staff.”
There’s so much, frankly, that isn’t known yet about risks.
When a person dies of COVID-19, is the virus dead, too?
“We don’t know the details around that.”
How long can the virus live inside a cadaver? “You need living cells for the virus to replicate. Once the person is dead, there’s no more viral replication. But nobody has looked to see how long the virus persists, how long is can remain viable in the body.”
Has a COVID-19 cadaver infected a pathologist?
“That’s not been documented.”
Can bodies still expel air with droplets that might be laden with the virus? “Not like that. But sometimes when you move bodies, you can get gas coming out. Usually from the stomach, gas bubbles moving up. That’s not a serious risk.”
The coroner’s office only does COVID-19-related autopsies when there’s a medico-legal issue, questions of causation such as whether there’s been neglect in a nursing home.
“For us, it’s not purely a medical research interest,” Pollanen says.
Which is why, from these findings, we might see an inquest called in the future over the multitude of nursing home COVID deaths in recent months.
“I can’t speak to that,” says Pollanen, who is also on the faculty of medicine at the University of Toronto, which trains pathologists from around the world. “The factual basis of the matter will become hugely relevant when we analyze this retrospectively.”
At the morgues, in Toronto and the regional offices, the autopsy, itself, follows classical protocols: internal examination, weighing of organs, taking samples for laboratory testing (the histology component). An adult lung that normally weighs 250 grams is so saturated with infection and pus in a COVID victim that it can weigh up to 1,000 grams.
The samples provide much broader insights than the swab sample the victim might have had while alive, which only confirms the virus is in the nose.
This is a clever and adventurous virus, biologically. Its ability to infect and actively reproduce in the respiratory tract, thwarting the body’s natural immune system, has stunned doctors.
Evidence suggests that after the virus attaches itself, the host cell snips the spike protein on the invader, triggering a chain of amino acids that help to pry open the host cell’s membrane so that the virus’s membrane can merge with it.
Once the invader’s genetic material gets inside the cell, as described in a recent article in the journal Nature, the virus commandeers the host’s molecular machinery to produce new viral particles.
Then, those “progeny” exit the cell to go and infect others.
Because, of course, the coronavirus doesn’t confine itself to ravaging the lungs; it can push kidneys into renal failure; cause blood clots that impede circulation to the lungs, heart or brain, leading to multiple organ failure as the immune system is overwhelmed.
The classical autopsy has become more sophisticated, primarily through conducting CT-scanning, which sometimes removes the necessity of opening up the body. But this has its limits. “There’s no substitute for going inside the body and examining tissue under a microscope,” Pollanen says. “Taking a sample to determine if the virus is present.”
The infection can be patchy or present throughout the lungs. “In other words, there may be areas that are involved and other areas that are not involved. Or it may be diffusely involved. That probably relates to the stage of progression.”
Pollanen carefully returns his tissue specimens to their tray. He knows why this poor man died.
The mysteries of COVID-19 are profound.
But for this victim, cause of death is not in doubt.
“It’s the most fascinating part of medicine,’ ” Pollanen says of his specialty. “Because it is the branch of medicine that ultimately underpins everything. Not only disease, but violence, neglect, everything.
“It all starts with the observations made at post-mortem examination. That’s the beginning of knowledge, of understanding.”