The COVID-19 pandemic has been found to cause disproportionate harm in patients with cardiovascular disease, especially among the elderly population, among other risk factors. However, a new study published on the preprint server medRxiv* in June 2020 is the first to report its clinical features in patients with aortic stenosis who have had a transcatheter aortic valve replacement (TAVR).
Heart Disease and COVID-19 Risk
Earlier studies have shown that up to 40% of patients who will need intensive care unit (ICU) admission because of severe or critical COVID-19 symptoms have a history of congestive cardiac failure. Patients with pre-existing cardiovascular disease may have a mortality rate of up to 36%, in contrast to the overall mortality of 3.4%.
Despite ample evidence that heart disease is directly implicated in the susceptibility and severity of COVID-19, there is not much knowledge about the risk of COVID-19 in patients with disease of the heart valves. The current study is therefore focused on patients with aortic stenosis who are treated with TAVR. It also seeks to detect biomarkers of increased risk for acquiring the virus or for developing severe disease, in the light of earlier observations that the blood group A is linked to a higher risk of COVID-19, but the O group to a lower risk.
TAVR and COVID-19 Risk
The study by researchers at the University Hospital of Strasbourg in France examined 702 patients who had TAVR between 2010 and 2019. Among them, the mean age was 82 years, and 44% were men. The most common underlying or coexisting conditions included coronary heart disease in 44%, atrial fibrillation in 40%, congestive cardiac failure in 36%, and peripheral artery disease in 27% of patients.
Over a quarter of these patients had cancer, while 12% had chronic obstructive pulmonary disease (COPD) and 17% chronic kidney disease, respectively. With respect to medications, almost half of them were on angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), half on statins, about 45% on anticoagulants and 53% on aspirin.
There were 22 patients who developed COVID-19, with 14 patients (64% of the COVID-19 patients) dying or requiring hospitalization with severe disease. On follow-up, they found that the mortality due to all causes in the study group was about 7%, while 3% died of cardiovascular causes. When only COVID-19 cases were analyzed, the all-cause mortality was much higher, relative to the rest of the group, at about 46% vs 6%. The rate of hospitalization was also much higher in the COVID-19 group, at 59%, vs. 2% in the other group.
Blood Group and COVID-19 Risk
The researchers also found that COVID-19 patients in the TAVR group were much more likely to have blood group A, at 82%, which is double its prevalence of 41% in the rest of the group. On the other hand, group O is found in 18% of the TAVR-COVID-19 subgroup, but 47% of those without COVID-19. Blood groups B and AB are not represented at all among COVID-TAVR patients but make up about 9% and 3% of the rest of the group.
When Rhesus group subtyping was observed, the researchers found that the A+ blood type is found in 68% of COVID-19 cases in this group, but 29% of the rest of the group. The A- blood type was not overrepresented, however.
Similar to the earlier trend, O+, B+, and AB+ blood types continued to be underrepresented in the COVID-19 group of TAVR patients, at 22%, 7%, and 3%, vs. 9%, 0 and 0 in TAVR patients without COVID-19. The O-, B- and AB- patients were also lower in proportion than expected.
Overall, patients with blood group A were 6 times more likely to develop COVID-19 than those with other blood groups, and over 3 times more likely to die of the disease, and had an 8 times greater risk of death or hospitalization.
Predictors of COVID-19 Risk in TAVR Patients
Could the risk of COVID-19 be predicted, asked the researchers? The answer they found was that the presence of blood group A predicted the risk of disease independent of other risk factors, with the odds increased by over 6 times. Both cancer and blood group A predicted severe disease or death due to COVID-19 in TAVR patients.
High Risk for Infection and Severe Disease
This study is the first to look specifically at the risk of COVID-19 in TAVR patients. The investigators demonstrate the high susceptibility of this group and the significantly increased risk with blood group A.
In fact, over 3% of this group developed COVID-19 as opposed to a general population prevalence of 24/10,000 in France. A local difference in the viral characteristics must be ruled out before it can be concluded that the history of TAVR confers a higher risk.
The mortality from COVID-19 was 45% in this study, which could perhaps be explained in terms of increased age, frailty, and other coexisting disease conditions in part.
The proportion of patients with severe disease was high, at 64%, which could possibly be due to the underexpression of the ACE2 receptor in patients with TAVR, as a result of the underlying vascular condition. This might cause accumulated angiotensin II activity, such as vasoconstriction, thrombosis, and inflammation
Earlier research has proved the increased susceptibility of blood group A to COVID-19, as well as the higher risk of severe disease. The current study confirms these findings and adds the risk of Rh typing as well, by showing that the latter antigen significantly increases the risk of COVID-19 in type A blood group.
Implications and Future Directions
More research is needed on whether the presence of anti-A antibodies limit the binding of the virus to the ACE2 receptor on the host cell and thus prevent infection. However, the A group is already related to a higher risk of cardiovascular disease, through a number of mechanisms such as the increased production of intercellular adhesion molecules, and von Willebrand factor. In contrast, the latter is cleaved in individuals with blood group O, reducing the risk of thrombosis in the latter if they are infected with SARS-CoV-2.
Despite the limitations of the current study, such as the small number of deaths and hospitalizations and the skewed sex ratio in different blood groups, the study shows that TAVR patients have a high risk of COVID-19, and that “the ABO blood group may be a useful laboratory parameter that should be taken into account for risk stratification during clinical work-up of patients with COVID-19.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.