Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19

Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19

This most likely explains the augmented response of the immune system and the more severe disease progression. However, certain hypertension-reducing drugs known as ACE inhibitors can have a beneficial effect. They not only lower blood pressure, but also counteract immune hyperactivation. The scientists have now published their findings in the journal Nature Biotechnology.

More than one billion people worldwide suffer from high blood pressure, or hypertension. Of the more than 75 million people around the world who have become infected with the SARS-CoV-2 virus worldwide so far, more than 16 million also have hypertension. These patients are more likely to become severely ill, which in turn results in an increased risk of death. It was previously unclear to what extent treatment with antihypertensive drugs could be continued during a SARS-CoV-2 infection - and whether they were more likely to benefit or harm the patients. This is because antihypertensives interfere with the exact same regulatory mechanism that the novel coronavirus SARS-CoV-2 uses to enter the host cell and trigger COVID-19.

The virus uses the receptor ACE2 as an entry portal into the cells, and the formation of this receptor is potentially influenced by the administration of antihypertensive drugs," explains the senior author. "We had therefore initially feared that patients receiving ACE inhibitors or angiotensin receptor blockers might have more ACE2 receptors on their cell surfaces and thus become more easily infected."

To clarify this suspicion, the scientists analyzed individual cells from the respiratory systems of COVID-19 patients who were also taking medication for high blood pressure. The author explains that they were subsequently able to give the all-clear: "We found that the drugs do not seem to cause more receptors to form on the cells. As a result, we do not believe that they make it easier for the virus to enter the cells in this way and thus cause the more severe course of COVID-19." On the contrary, cardiovascular patients taking ACE inhibitors actually displayed a lower risk of becoming severely ill with COVID-19. In fact, they displayed almost the same level of risk as COVID-19 patients without cardiovascular problems.

The blood of hypertensive patients usually shows elevated levels of inflammation, which can be fatal in the case of a SARS-CoV-2 infection. "Elevated inflammation levels are always a warning signal that COVID-19 will be more severe, regardless of any cardiovascular issues," explains the author. The scientists therefore employed single-cell sequencing methods to investigate the immune response of hypertensive patients with COVID-19.

"We analyzed a total of 114,761 cells from the nasopharynx of 32 COVID-19 patients and 16 non-infected controls, with both groups including cardiovascular patients as well as people without cardiovascular problems," reports the research group leader in the lab. "We found that the immune cells of the cardiovascular patients displayed strong pre-activation even before infection with the novel coronavirus," explains the author. "After contact with the virus, these patients were more likely to develop an augmented immune response, which was associated with the severe disease progression of COVID-19. However, our results also showed that treatment with ACE inhibitors, though not with angiotensin receptor blockers, could prevent this augmented immune response following infection by the coronavirus. ACE inhibitors could thus reduce the risk of patients with hypertension from experiencing severe disease progression."

Furthermore, the scientists found that the anti-hypertensive drugs can also impact how quickly the immune system is able to reduce the viral load, i.e., the concentration of the virus in the body. "Here, we observed a clear difference between the different forms of treatment for high blood pressure," notes another author. "In the patients treated with angiotensin II receptor blockers, the reduction in viral load was significantly delayed, which could also contribute to a more severe course of COVID-19. We did not observe this delay in the patients who were receiving ACE inhibitors to treat their hypertension."