High blood pressure is one of the key risk factors for developing severe illness from COVID-19, but understanding that connection has proven difficult beyond simple, observational studies.
Researchers at The University of Toledo hope to change that.
Using CRISPR gene-editing technology, Dr. Bina Joe and her team from the College of Medicine and Life Sciences and the Center for Hypertension and Precision Medicine have engineered a new rat model that is prone to hypertension and is testing its susceptibility to COVID-19.
The project has received a two-year grant from the National Institute of Allergy and Infectious Diseases totaling $425,000.
Rats, which are a primary platform for studying hypertension, do not naturally contract the virus that causes COVID-19. To create an effective model, the UToledo team engineered the genome of a genetically hypertensive rat to swap out the rat’s own ACE2 receptor and replace it with the human receptor.
The ACE2 receptor is what allows the SARS-CoV-2 virus to bind and infect cells.
While animal models for COVID-19 have allowed a range of research, UToledo’s newly developed model would be the first for studying COVID-19 in the context of hypertension.
“There are pathologies in the cardiovascular system that are for unknown reasons linked to COVID-19,” said Joe, Distinguished University Professor and chair of the Department of Physiology and Pharmacology and the project’s lead investigator. “To understand this, there are fundamental research questions that we have so far been unable to study. If successful, this model could be a platform to add significantly to our knowledge of the link between COVID-19 and hypertension.”
The NIH funding will allow UToledo researchers to explore and evaluate the effectiveness of their model. As a secondary goal, the team also will test a hypothesis that differences in gut microbiota may be why some individuals experience gastrointestinal symptoms with COVID-19 while others do not.
The key, however, is finding a way to study the relationship between hypertension and susceptibility to COVID-19.
A recent study published in the journal Anaesthesia, for example, found that patients with a history of high blood pressure who were admitted to an intensive care unit with COVID-19 were 54% more likely to die.
Understanding why hypertensive patients are at such an elevated risk for COVID-19-related complications and death could potentially help clinicians to improve those outcomes.
After leveling off in June, new cases of COVID-19 are again on the rise in the United States as the more transmissible delta variant has become the dominant strain. And while daily death totals from COVID-19 remain far below their peak, the virus still claims between 200 and 300 lives a day.
“We’ve come out of it with vaccines, but vaccines alone are not going to be enough,” Joe said. “We need to know what’s causing these pathologies. Animal models are indispensable for this field of study.”
Joe is working on the project with co-investigators Dr. Jason Huntley, associate professor of medical microbiology and immunology, and Dr. Saurabh Chattopadhyay, assistant professor of medical microbiology and immunology, in the College of Medicine and Life Sciences.