COVID-19 Autopsies Hint at Direct Viral Infection of the Heart
Two-thirds of patients in the small postmortem series had evidence of active virus in cardiac tissue, but questions remain.
The myocardial injury that has been documented in patients with COVID-19 may stem from active virus replicating in heart tissue, a German autopsy study suggests.
In the paper, published online July 27, 2020, in JAMA Cardiology, the researchers say it appears that the presence of SARS-CoV-2 in cardiac tissue “does not necessarily cause an inflammatory reaction consistent with clinical myocarditis,” and that the “long-term consequences of this cardiac infection requires further investigation.”
Speaking with TCTMD, Gregg C. Fonarow, MD (University of California, Los Angeles), said it is important to bear in mind that the autopsy reports from COVID-19 patients published to date, including this one, have all been relatively small and either single-center or pooled data in select, most elderly patients.
“But on the other hand, they do give important insights for which there are clinical correlates,” he added. “Specifically, with this autopsy series, it's enlightening because from the very earliest reports coming out of China regarding COVID-19, there were elevations in cardiac troponins, and there was a lot of puzzlement as to what that actually meant.”
Fonarow, who along with Clyde W. Yancy, MD (Northwestern University, Chicago, IL), wrote an editorial accompanying the study, said if anything, “it’s reassuring that we're, at least in these cases, not seeing acute myocarditis with the frequency that some people speculated very early on when reports started to come in.” But it also shows that there is more cardiac involvement than initially suspected, some of it clearly subclinical, he added.
Interstitial Cell Involvement
Hamburg, Germany, where the autopsies were performed, has mandated full-body postmortems for all COVID-19 deaths in the city, senior study author Dirk Westermann, MD (University Heart and Vascular Centre Hamburg), noted in an email. TCTMD has previously reported on a smaller series of autopsies from the Hamburg region that described lung weights that ranged from two- to fourfold higher than average.
In the new report, Westermann and colleagues led by Diana Lindner, PhD (University Heart and Vascular Centre, Hamburg, Germany), used reverse transcriptase-polymerase chain reaction testing to identify SARS-CoV-2 RNA in the myocardium of 24 of 39 patients (61.5%) who died in April 2020. All had tested positive for the virus prior to death, and none had clinically fulminant myocarditis. The median age was 85 years and the cause of death in 89% was pneumonia. The cardiac tissue included two specimens from the left ventricle.
In 16 cases, a viral load above 1,000 copies per μg RNA was noted. Those patients also had increased proinflammatory genes. Virus replication in the myocardium was documented in five patients with the highest virus load.
Lindner and colleagues also conducted in situ hybridization of SARS-CoV-2 RNA and found virus present in interstitial cells or macrophages within the cardiac tissue rather than in myocardiocytes.
“Importantly, fulminant myocarditis was not associated with SARS-CoV-2 infection in this study with no significant change in transendothelial migration of inflammatory cells in the myocardium in patients with high virus load vs no virus,” they write. “In the published cases in which myocardial inflammation was present, there was also evidence of clinical myocarditis, and therefore the current cases underlie a different pathophysiology.”
While the findings provide important new clues as to the possible mechanism of myocardial injury in COVID-19 infected patients, Lindner and colleagues say the clues provided by the autopsies are limited and that “future studies are needed to reveal whether cytokine expression correlates with cardiac dysfunction during the disease and its aftermath.” They also question whether myocardial biomarkers might be upregulated due to the SARS-CoV-2 infection.
Indeed, the literature to date has been mixed on the extent to which this virus is infiltrating the heart, with another recent autopsy analysis reported by TCTMD making the case that not all patients with cardiac manifestations of COVID-19 show signs of direct viral infiltration. Indeed, 15 of the patients in the current autopsy analysis showed no SARS-CoV-2 RNA in the myocardium.
According to Fonarow, many avenues for additional research can grow out of these sorts of clues, especially in the current environment where there is still so much left to learn about COVID-19, its management, and any lasting impact on the heart.
“It would be really interesting with therapies like dexamethasone, for example, to look at . . . whether we see a corresponding decline in troponin levels in those who respond that parallel that time course,” he said. Further insight from autopsy studies showing how COVID-19 impacts the heart also may help lead to the creation of strategies involving cardioprotective medications. That’s an idea also put forward by the authors of another article out this week in JAMA Cardiology that found evidence of myocardial inflammation on MRI in recovered COVID-19 patients more than 2 months after their initial positive COVID-19 test, even those who never experienced severe illness.
“Even in that period where clinically patients are recovering, there’s still evidence of myocardial inflammation, reflecting this injury,” he noted. “Those findings also need to be replicated to see how generalizable they are and [if] we see that same frequency of involvement of the heart through cardiac MRI.”
Lindner D, Fitzek A, Bräuninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol. 2020;Epub ahead of print.
Yancy CW, Fonarow GC. Coronavirus disease 2019 (COVID-19) and the heart— is heart failure the next chapter? JAMA Cardiol. 2020;Epub ahead of print.
- Westermann reports personal fees from AstraZeneca, Bayer, Novartis, and Medtronic.
- Yancy reports no relevant conflicts of interest.
- Fonarow reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck, and Novartis.