An investigation into why asthma sufferers are less likely to contract COVID-19 is one of several aims for research funded through a $7.16 million National Institutes of Health cooperative agreement with the Asthma and Airway Disease Research Center at the University of Arizona Health Sciences.

Early in the pandemic, scientists learned that one of the ways the SARS-CoV-2 virus infects cells is through the angiotensin-converting enzyme 2 (ACE2) receptor. The ACE2 receptor is an enzyme that, among other things, helps relax veins and lower blood pressure. Last summer, Monica Kraft, MD, deputy director of the Asthma and Airway Disease Research Center and professor and chair of the UArizona College of Medicine – Tucson’s Department of Medicine, led a study that showed the proteins governing asthma-induced inflammation reduce ACE2 expression.

“It seems having asthma confers some degree of protection against COVID-19, because the ACE2 receptor is reduced in asthma,” said Dr. Kraft, who also is a member of the BIO5 Institute. “We’ve seen a lot fewer asthma exacerbations during the pandemic. And when you look at all the comorbidities of patients admitted with severe COVID-19, asthma does not stand out as one of them.”

Respiratory infections caused by viruses can make asthma worse and are challenging to treat due to lack of effective antiviral therapy. Under the National Institute of Allergy and Infectious Diseases cooperative agreement, Dr. Kraft and the research team will seek to learn more about viral interactions as part of their ongoing research into the molecular pathways that control inflammation in asthma. They will focus on three viruses and how three natural immune responses might protect against them.

In the first project, researchers will test the ability of fat and protein components of the pulmonary surfactant, a thin layer of fluid secreted by the lung’s cells to reduce tension during breathing, to inhibit rhinovirus C. In addition to causing the common cold, rhinovirus C is a known exacerbator of asthma that can cause severe disease.

The second project will focus on a toll-like receptor interacting protein that initiates immune responses. Researchers hope to determine how it protects airways from severe forms of viral infection, specifically the influenza A virus, in asthma.

The third project builds on earlier research into surfactant protein A and cytokines. Surfactant protein A has anti-inflammatory effects in asthma, while cytokines are small proteins that activate the immune system. Both may limit COVID-19 by reducing the expression of the ACE2 receptor. Researchers hypothesize that synergy between the two may offer protection from COVID-19 by dampening the initiation and the effector phases of SARS-CoV-2 infection.

“The Asthma and Airway Disease Research Center team has made important discoveries in understanding asthma patients’ reactions to allergens and infectious agents,” said University of Arizona President Robert C. Robbins, MD. “I am very glad to see the impact of their incredible research advance with these projects, which have the potential to help millions of people around the world who suffer from asthma while also expanding our knowledge of SARS-CoV-2 and COVID-19. I am very excited to see the results.”

The projects will be conducted in collaboration with National Jewish Health, the University of Colorado Denver, Cedars-Sinai Medical Center and the University of California, Los Angeles.

This research is supported by the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health (U19AI125357).