Q&A: Does asthma mitigate the risk for COVID-19?

In a study conducted in collaboration with National Jewish Health, University of Colorado Denver, Cedars-Sinai Medical Center and University of California, Los Angeles, researchers are investigating how three separate viruses interact with the biological mechanisms that control inflammation in asthma.

In an interview with Healio, Monica Kraft, MD, Robert and Irene Flinn endowed chair in medicine at University of Arizona College of Medicine, Tucson and deputy director of the Asthma and Airway Disease Research Center, discussed what is known about the link between asthma and other respiratory diseases and what researchers hope to discover about its link to COVID-19.

Healio: What is already known about the connection between asthma and contracting certain respiratory diseases?

Monica Kraft

Kraft: It's an interesting topic because many viral illnesses — common viruses include rhinovirus, influenza, respiratory syncytial virus (RSV) and parainfluenza — can exacerbate asthma, making it worse and causing asthma attacks. There are data showing that early-life infections with specific viruses, like rhinovirus and RSV, can hasten the presentation of asthma in those children who are at risk, who have a family history of asthma or allergy, etc. That's the more common school of thought, and that's what makes this observation we've had with SARS-CoV-2 really interesting. Asthma does not appear to be a huge risk factor at this point, but we're still learning, and this field is very fluid.

Healio: What has been observed so far about the association between asthma and COVID-19?

Kraft: When we first looked at papers coming out of Wuhan, China and Europe about COVID-19 in the spring of 2020, we noticed that asthma and allergy weren't listed as comorbidities along with diabetes, heart disease, obesity, etc. One reason that asthma and allergy may not necessarily be associated with severe COVID-19 is because of the ACE2 receptor, which is one of the major receptors that the virus uses to enter cells. For reasons that are separate from this infection, ACE2 levels are reduced in allergic or eisinophilic asthma, so therefore the virus has less opportunity to infect the cell. That's one hypothesis, but we think that's the link, because the other common viruses that can cause asthma attacks do not use ACE2 receptors to get into the cell.

There's also an interesting body of literature suggesting that some of the medications we use for asthma such as inhaled corticosteroids, which is used first line, may be protective in asthma. The challenge is there aren’t a lot of trials on this directly, so this is more observational.

Healio: What will the three projects of the study entail?

Kraft: One project is looking at the relationship of asthmatic inflammation to SARS-CoV-2 specifically in terms of surfactant protein A, which we think has therapeutic properties in asthma. Now we're also looking at whether it may be protective in SARS-CoV-2, and we have some very early data there.

The second project is led by investigator Hong Wei Chu, MD, at National Jewish Health in Denver, and he and his group are looking at another protein made by the lung called toll-interacting protein, or TOLLIP. The hypothesis is that TOLLIP decreases the inflammation and is protective in the setting of viral infections. But, TOLLIP may not always be 100% functional depending on somebody's genetics, so the researchers are evaluating TOLLIP-deficient cell models and TOLLIP-deficient mice to understand the role of TOLLIP in the setting of viral infection, and influenza in particular.

Mari Numata-Nakamura, MD, PhD, and Dennis R. Voelker, PhD, also at National Jewish Health, are leading the third project, which is looking at another aspect of surfactant. They're looking at the lipid portion of surfactants and its protective properties in the setting of rhinovirus infection, because rhinovirus C can cause very significant asthma attacks.

We each have a part of the innate immune system, which is very large, so we're picking three aspects of it and trying to study in more detail what it means for asthmatics. What are the protective entities that the lung makes to protect asthmatics? Why do they go awry?

Healio: How do you think your findings will be helpful in the fight against COVID?

Kraft: I think it will just add one more piece to the puzzle about this virus, which seems to do a lot of very different things compared with many of the viruses that we’re vaccinated against. The findings should add additional information because we're still trying to understand who's at risk and what we can do to modify risk factors and protect our patients. The more we understand about the interaction between our underlying health and SARS-CoV-2, the better. We want to understand if asthma is protective across the board or if it’s just certain kinds of asthma. We also want to get a better understanding of where the vaccine comes into this and if asthmatics respond to the vaccine well, which would be very important to know for public health reasons.

Healio: Anything else you would like to mention that we haven’t covered?

Kraft: Yes, there will be a paper coming out in early 2022 on the IMPACT trial, sponsored by NIH. This is a nationwide study done at centers all around the country, for which we have recruited about 1,000 patients who were hospitalized with COVID-19 from spring 2020 through June 2021. We’re looking at the various disease trajectories, as well as risk factors and disease processes that are associated with more severe or less severe courses of COVID-19. We also are doing a separate sub-study looking at those patients with asthma, who might have a more benign course. It will be one of the largest cohorts really studied intensively from a clinical perspective and also from an immunologic perspective. There'll be a number of papers coming out from this group, but the clinical paper should be coming out in early 2022.

For more information:

Monica Kraft, MD, can be reached at kraftm@email.arizona.edu.