Create PDF

Both small vessel thrombosis and large vessel thrombosis in the lungs and heart are evident at autopsy. “We’ve seen that in several cases, and that does resonate with the clinicians who are finding it difficult to control chronic clotting in the patient. There is definitely a blood clot component to the disease, and we are seeing a lot of it in the lungs.”

The clotting in the larger vessels includes classical pulmonary emboli and pulmonary thrombosis, he says. “But at autopsy we’ve also seen some coronary thrombosis.” Unlike other diseases, there is a quantity of the smaller clotting in the small vessels of the lung and also in the capillary bed of the lung present in COVID patients. “Although that type of clotting may happen in other acute illnesses, it is particularly prominent in a large subset of our patients.”

A second dramatic feature of COVID patients in autopsy is that “the lung weights of these patients are exceptionally high. That is part of ARDS in general, but it is very notable with COVID and, again, the novelty is the presence of these microthrombi and platelet thrombi in the microcirculation” Dr. Borczuk says.

From the autopsy perspective, “COVID is showing changes that we’ve seen individually in different diseases involving respiratory distress syndrome. But it’s the severity and the combination of all these different injuries—very heavy lungs, platelet microthrombi in the capillary bed, and large airway ulcerating inflammatory lesions— that make COVID unique.”

The existing literature on COVID-19 autopsy supports the same things he has seen, but mostly the thrombotic complications. The large airway lesions have been less noted; he is now planning to collect enough cases to present this aspect of COVID for publication in the coming weeks.

“The question I am interested in is what is the unique injurious effect on the lung that is resulting in this quite accelerated severe disease with thrombosis.” Modern molecular biology techniques, gene and protein expression, looking at protein phosphorylation and pathways of activation in the blood, will likely be able to shed light on this, he says.

Initial observations have been made about what may be causing injury of the vascular bed. “But we need to find out more. What about those epithelial cells—how are they being damaged such that the lungs are more prone to thrombosis? What is the pathway of that thrombosis? Can it be blocked? Can it be blocked through standard anticoagulation or is it going to require a more targeted approach to get us to the cause of the initial injury?”

Autopsy findings on these questions may not immediately change therapy for COVID patients, but they have started to guide thinking about what would be a reasonable therapeutic approach, he says.

Another line of inquiry Dr. Borczuk is pursuing relates to undetected COVID-19. “I’m looking at our autopsy cases going back a couple of months prior to our index case to see whether there are some sudden death cases that we attributed to some other cause or perhaps thought may have been COVID-related.”

“Good tests that work in autopsy material—that is, in situ hybridization and maybe some PCR testing on paraffin tissue—are still in development. When we have a robust assay in that way, and I think we’re getting very close to that, we’ll be able to start interrogating older cases and looking for definitive evidence of COVID infection.”

Dr. Borczuk finds that the autopsy service has worked well with the clinical laboratory in uncovering more details about patients’ COVID-related conditions. “We can do nasal swabs in the postmortem setting if we need to do a confirmatory test, and we have done that. Blood cultures, which we’ve done at autopsy, have been very informative because, again, it may be that patients are developing secondary infections in the hospital and the lung disease may not be due to COVID.

“But while we may have seen one or two patients who definitely have more classical bacterial pneumonias, the ability to have antemortem and postmortem culture has made it possible for us to definitively state which patients had a bacterial infection and which ones didn’t. And, of course, the development of tissue-based PCR tests will be a critical interlaboratory collaboration.”

The need to prepare for future pandemics is also part of what makes answering those questions important. “We need to get answers about the virus as it causes severe lung injury,” he says. “But we need to also start learning what might be the features of this virus in our samples as we move forward,” now that the pandemic lockdown conditions are being eased.

“As we start seeing patients and patient material again, we will need to recognize the complications of this virus in people who perhaps are not as severely ill as the people we have seen so far,” Dr. Borczuk says. In addition, physicians should begin to develop some understanding about whether there will be any long-term sequelae in patients who recover, ”especially in the lung, but not exclusively the lung.”

“Then we will want to see if there are any features that may alert us to a new outbreak in the future. As pathologists who look at tissue and pathologists who do clinical pathology, we will need to have a really good armamentarium of tests that can recognize this disease in its myriad forms and the different ways it causes tissue injuries. But we also need to have robust testing to make sure we are detecting the disease early if there is a future outbreak.”

Anne Paxton is a writer and attorney in Seattle.