Not Just a Respiratory Disease – The Cardio-COVID Link
Early in the coronavirus pandemic, evidence emerged that COVID-19 was not just a disease of the respiratory system as initially thought. It became clear that people with underlying cardiovascular problems, such as prior heart failure, coronary artery disease, or hypertension, were more susceptible to severe infection with SARS-CoV-2. There was also evidence to suggest that many patients who were hospitalized with COVID-19 showed markers of cardiac injury.
In July 2020, two pivotal studies, published in JAMA Cardiology, suggested that COVID-19 might have a prolonged impact on heart health, even in patients whose illness was not severe enough to require hospitalization.
In the first study,1 researchers examined the MRIs of 100 patients recently recovered from COVID-19 infection and compared them to those from healthy individuals who were not infected with the virus. The team found abnormalities in the hearts of 78% of recently recovered patients and ongoing myocardial inflammation in 60%, independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.
The second study2 evaluated the presence of SARS-CoV-2 in the myocardial tissue of 39 COVID-19 autopsy cases. The researchers detected high levels of the virus in 24 (61.5%) of these patients. Furthermore, the viral load was above 1,000 copies per μg RNA in 41% of patients.
Uncovering the Connection
Since these findings were reported, physicians and researchers have continued to explore the relationship between SARS-CoV-2 infection and patients’ hearts.
A study3 conducted by researchers from the University of Cambridge, led by Anthony P. Davenport, showed that expression of the genes involved in viral entry were upregulated in aged cardiomyocytes. The researchers said this might explain why older people appear to be particularly susceptible to the cardiovascular complications associated with COVID-19. The team concluded that their findings could inform future studies into the relationship between cardiomyocytes and COVID-19.
Just six months later, Davenport and colleagues published a second study4 outlining a screening platform which could be used to identify inhibitors of infection. The aim of the study was to confirm that their model expressed the protein machinery critical for SARS-CoV-2 infection and then to screen for novel therapeutic agents. The new platform, which used human embryonic stem cell-derived cardiomyocytes (hESC-CMs), helped identify two novel inhibitors of SARS-CoV-2 viral entry, namely Benztropine and DX600.
“Our results provide a platform to generate high quality data in pre-clinical studies to justify translational research in animal models of acute respiratory distress syndrome and the repurposing of current drugs for clinical trials,” said Davenport et al.
Full details of the screening platform and the experimental approach used by Davenport’s team can be found here.
- Puntmann V, Carerj M, Wieters I, Fahim M, Arendt C, Hoffmann J et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiology. 2020;5(11):1265.
- Lindner D, Fitzek A, Bräuninger H, Aleshcheva G, Edler C, Meissner K et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiology. 2020;5(11):1281.
- Robinson E, Alkass K, Bergmann O, Maguire J, Roderick H, Davenport A. Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes. Journal of Molecular and Cellular Cardiology. 2020;147:88-91.
- Williams T, Colzani M, Macrae R, Robinson E, Bloor S, Greenwood E et al. Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection. 2021;.