Patient with hypertension or cardiovascular disease has critically progressed his disease with COVID-19

Patients with COVID-19 who also have high blood pressure are more likely to fall seriously ill, which also puts them at greater risk of death.

Scientists from the Berlin Institute of Health (BIH) and Charité – Universitätsmedizin Berlin, together with partners in Heidelberg and Leipzig, have now discovered that the immune cells of patients with hypertension are already pre-activated and that this pre -activation is greatly improved under COVID-19.

This most likely explains the increased immune system response and the more severe progression of the disease. However, some antihypertensive drugs called ACE inhibitors may have a beneficial effect.

They not only lower blood pressure, but also neutralize immune overactivation. Scientists have now published their results in the journal Biotechnology of nature.

Over a billion people around the world suffer from high blood pressure or hypertension. Of the more than 75 million people worldwide who have been infected with the SARS-CoV-2 virus worldwide to date, more than 16 million also suffer from hypertension.

These patients are more likely to become seriously ill, which in turn leads to an increased risk of death. It was not previously known to what extent antihypertensive therapy could be continued during SARS-CoV-2 infection – and whether they were more likely to benefit or harm patients.

This is because antihypertensive drugs interfere with exactly the same regulatory mechanism that the novel coronavirus SARS-CoV-2 uses to enter the host cell and trigger COVID-19.

Professor Ulf Landmesser is Medical Director of CharitéCenter 11 for Cardiovascular Diseases, Director of the Medical Department of Cardiology and BIH Professor of Cardiology on the Charité Benjamin Franklin Campus in Berlin. He recognized early on that the patient with hypertension or cardiovascular disease often had particularly critical disease progression with COVID-19.

The virus uses the ACE2 receptor as a gateway into cells, and the formation of this receptor is potentially influenced by the administration of antihypertensive drugs. We therefore initially feared that patients receiving ACE inhibitors or angiotensin receptor antagonists would have more ACE2 receptors on the surface of their cells and thus become more easily infected. “

Ulf Landmesser, professor, medical director of CharitéCenter, director of the medical department of cardiology, BIH de la Charité

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To clarify this suspicion, the scientists analyzed individual cells in the respiratory systems of patients with COVID-19 who were also taking medication for high blood pressure.

Dr Sören Lukassen, a scientist in Professor Christian Conrad’s group at the BIH Digital Health Center, explains that they were then able to give the green light: “We found that the drugs did not seem to cause the formation of more than receptors on cells Therefore, we do not believe that they facilitate the entry of the virus into cells in this way and thus cause the more severe course of COVID-19. “

On the contrary, cardiovascular patients taking ACE inhibitors actually had a lower risk of becoming seriously ill with COVID-19. In fact, they had almost the same level of risk as COVID-19 patients without cardiovascular issues.

Severe course of COVID-19 linked to pre-activation of the immune system

The blood of hypertensive patients usually has high levels of inflammation, which can be fatal if infected with SARS-CoV-2. “High levels of inflammation are always a warning signal that COVID-19 will be more severe, regardless of cardiovascular issues,” says Landmesser.

Scientists therefore used single-cell sequencing methods to study the immune response of hypertensive patients with COVID-19.

“We analyzed a total of 114,761 nasopharyngeal cells from 32 COVID-19 patients and 16 uninfected controls, both groups including cardiovascular patients as well as people without cardiovascular problems,” reports Dr. Saskia Trump, group leader of research in the lab of Irina Lehmann, who is BIH Professor for Environmental Epigenetics and Lung Research.

“We found that the immune cells of cardiovascular patients showed strong pre-activation even before infection with the novel coronavirus,” explains Lehmann.

“After contact with the virus, these patients were more likely to develop an enhanced immune response, which was associated with severe progression of COVID-19 disease. However, our results also showed that treatment with inhibitors of the ACE, but not with angiotensin receptor blockers, could prevent this enhanced immune response following infection with the coronavirus. ACE inhibitors could thus reduce the risk of patients with hypertension to experience severe progression. of disease.

Delayed reduction in viral load

In addition, scientists have found that antihypertensive drugs can also have an impact on how quickly the immune system is able to lower the viral load, which is the concentration of the virus in the body. “Here we have seen a clear difference between the different forms of treatment for high blood pressure,” notes Roland Eils, director of the BIH Digital Health Center.

“In patients treated with angiotensin II receptor antagonists, 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 patients who received ACE inhibitors to treat their hypertension. “

Interdisciplinary collaboration accelerates research

More than 40 scientists worked at breakneck speed on this in-depth study. “The ability to respond quickly to urgent questions during the ongoing pandemic requires interdisciplinary collaboration among many engaged people,” explains Eils.

“COVID-19 is such a complex disease that we have brought together experts from cardiology, immunology, virology, pulmonary medicine, critical care and informatics for this study. Our goal was to provide a scientifically valid answer as quickly as possible to the question of whether simultaneous treatment with ACE inhibitors or angiotensin receptor antagonists could have beneficial or even adverse effects during the COVID pandemic. -19. “

No evidence of increased risk of infection

Thanks to this study, the teams of BIH, Charité and collaborating institutions in Leipzig and Heidelberg can now reassure both patients and the doctors who treat them: “Our study does not provide any evidence that antihypertensive treatment is increasing. the risk of infection with the new coronavirus ”, explains Ulf Landmesser, summarizing the results.

“However, treatment of hypertension with ACE inhibitors may be of greater benefit for patients with COVID-19 than treatment with angiotensin II receptor blockers – a hypothesis that is currently being investigated further. in randomized trials. “