CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anne Ford
October 2020—Autopsies conducted at University Medical Center in New Orleans on 22 patients who died from SARS-CoV-2 infection found not the expected typical inflammation of the heart muscle associated with myocarditis but instead scattered individual myocyte necrosis.
Early reports suggested that the heart was a primary target of the infection. In one study, conducted in January and February in Wuhan, China, nearly 20 percent of 416 patients hospitalized with COVID-19 were found to have cardiac injury (Shi S, et al. JAMA Cardiol. 2020;5[7]:802–810).
Those findings, however, have not been borne out in the experience of Richard S. Vander Heide, MD, PhD, MBA, professor of pathology at Louisiana State University School of Medicine and director of autopsy services, University Medical Center New Orleans. There, he says, “a large majority of the COVID-19-related deaths to date have been primarily due to lung damage and the resulting respiratory failure.”
Still, examinations of the heart during COVID-19 autopsies at University Medical Center have uncovered striking findings—enough of them to make Dr. Vander Heide predict: “I think as we go forward what we’re going to find is that the heart may be a long-term consequence of COVID infection.”
Given the myocarditis mentioned in early reports, myocarditis was naturally one of the things that Dr. Vander Heide and his colleagues at University Medical Center looked for when performing autopsies on 22 COVID-19 patients (10 male, 12 female; 86 percent African American; median age 68.5 years).
Specifically, “we were interested to find out whether there was a lymphocytic infiltrate into the heart associated with damage to the heart cells themselves, which is what, classically, people associate with myocarditis,” he says. “And we did not find anything like that. We did not find typical myocarditis in any way, shape, or form. I kept looking and looking and looking.”
All that looking did pay off, albeit in an unexpected way. With routine H&E staining, the team found what Dr. Vander Heide calls “swelling or increased prominence” of endothelial cells in the capillaries. Additional immunostaining on a subset of the sections for lymphocytes, endothelial cells, and DNA/RNA, however, didn’t yield anything striking. Or did it?
“As we saw in the H&E, we did not see significant numbers of lymphocytes in the myocardium,” he says. “What we did see is that the lymphocytes present seemed to be centered on the blood vessels, if anything. So that confirmed our impression that myocarditis, as it’s typically described, really isn’t present, and what we were seeing was something involving the small blood vessels and the endothelium.”
At that point, the team turned to electron microscopy. “In the initial SARS-CoV infection in 2002, there were reports that about 30 percent of patients who had died from SARS had virus identified—or at least viral sequences identified—in the myocytes themselves,” he says. “And so we were interested to find out whether there was virus present in the myocytes in SARS-CoV-2.” Samples from six COVID-19 autopsies were sent to the University of Delaware’s electron microscopy laboratory.
“We did a pretty exhaustive look,” Dr. Vander Heide says, and he’s glad they did. As he and colleagues wrote in a research letter published July 21 online ahead of print, “Electron microscopy revealed particles consistent with SARS-CoV-2 virus in the myocardial endothelial compartment, pneumocytes, and renal tubular epithelium, but not in the myocytes of six patients examined by EM” (Fox SE, et al. Circulation. 2020;142[11]:1123–1125).
“I was very excited,” he says. “This confirmed our thinking that maybe it’s the endothelium that is the target in the heart. A lot of data has come out in the last couple of months [showing] that the endothelium is certainly a target for SARS-CoV-2 infection in many different organs. I don’t think it’s a stretch to think that the heart would certainly be one of the targets, that the virus uses the endothelial cell to gain access to the heart.”
Dr. Vander Heide’s concerns about potential long-term cardiovascular consequences of COVID-19 appear to be reinforced by a case study that he and his colleagues reported (Fox SE, et al. Ann Intern Med. Published online ahead of print July 29, 2020. doi:10.7326/L20-0882). The patient was a 31-year-old female African American who was admitted to University Medical Center for treatment of COVID with typical comorbidities such as obesity, diabetes, and hypertension.
In primary SARS-CoV-2 infection, there is no significant lymphocytic infiltrate. Neutrophils are noted in collections within small vessels (blue arrows) and plump endothelial cells (yellow arrowheads) are common.
“When she was discharged, she didn’t have a fever, and her oxygen levels were quite high on room air,” he says. “Twelve days later she came back with a sudden fever, neck pain, nausea and vomiting, and sinus tachycardia. They did some workup and found that she had bilaterally enlarged parotid glands—which they thought might be mumps, which is interesting—and some other nonspecific inflammatory responses in the tissue and also in the laboratory values.” PCR was negative for SARS-CoV-2. While being evaluated for admission, the patient died after developing hemodynamic instability and ventricular fibrillation.
“We were very interested in that case because that was the first one at the time where we had someone who had had COVID, had recovered, and now had presented later with other kinds of symptoms,” Dr. Vander Heide says.