Sleep, inflammation, and COVID-19

Breathing, sleeping, and good health go hand in hand. People with lung diseases and allergies often have problems getting a quality, healthy night’s sleep which in turn can lead to further health challenges. Physician-scientist Dr. Sairam Parthasarathy is a BIO5 member who works at the intersection of chronic illness and sleep. Dr. Parthasarathy is a professor of medicine and clinical translational sciences at the University of Arizona, as well as the College of Medicine’s Division Chief of Pulmonary, Allergy, Critical Care and Sleep Medicine. He’s also the medical director of the Banner – University Medical Center Tucson Center for Sleep Disorders and director of the UArizona Health Sciences Center for Sleep and Circadian Sciences.

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Your research primarily focuses on comparing the relationship between sleep and inflammation in people who are critically ill and those in the general population. Tell us a little bit more about the general nature of your research and how you got into that area.

My background was originally in critical care in the ICU, and then I transitioned into doing an additional fellowship in sleep after my fellowship. When I was working with my mentor, I wanted to combine those areas - I wanted to look at sleep in critically ill patients, specifically in ICU patients who are supported by mechanical regulators.

We know that sleep is important for health and for the immune system, so in these people who are hospitalized on a ventilator with tubes out of every orifice and in a very uncomfortable and acutely sick situation are highly likely to disturbed and very deranged sleep. Therefore, the immune system can get affected, and if there's anyone who needs an immune system, it’s someone in the ICU with an infection who is fighting for their life. 

Subsequently, I got so enamored with the brain and how complex of an organ it is, and even though I began as a specialty interest in the lungs, the interaction with the brain and the lungs in terms of control of breathing and sleep got me very much interested in that area. That's how I tried to create a new area of research looking at sleep in ICU patients.

The connection there is that the way in which sleep disturbances worsens the risk for bodily harm and recovery is by affecting the immune system, so that's why I decided to study inflammation - it's an easily accessible way of studying the immune system in these people. 

Now we know that that's hugely relevant in the era of the COVID pandemic and vaccination, how important the immune system is, and I think the layperson’s understanding of immune system has skyrocketed in this these two years, so I guess I see that as a silver lining in all of this.

Here at BIO5, we had the facilities and the resources to be able to quickly pivot to address the COVID-19 pandemic, and you were one of those people who took on that challenge. Can you talk about your role in working to address the pandemic through your work?

I’ll begin talking about what we were doing with regards to sleep and inflammation. Previously, along with collaborators here at the University of Arizona, specifically at the Asthma & Airway Disease Research Center, we looked at biobank samples going back to 1971 as well as in 1983, when better integration sleep questionnaires were administered to the patients and followed up through 2011. 

In that particular study, we found that people with persistent insomnia for at least five years had greater levels of inflammation and they were more likely to die from cardiovascular death. There is this thinking that inflammation is like the icepick that actually breaks the ice (blockages in blood vessels), so inflammation is responsible for breaking those blocks and causing clot formation to ultimately cause a heart attack.

The ice patch is formed by high amounts of cholesterol consumption, but you need something to break that patch and for that you need inflammation. The inflammation comes from various sources, one of them is inadequate sleep, in this case insomnia.

Similarly, in ICU patients, we were trying a sleep intervention prior to the pandemic. We wanted to see if we could improve sleep with a novel sedative, which acts very differently than conventional sedatives, and in turn reduce inflammation. We showed that it does reduce inflammation.

Now fast forward to the pandemic when we were still allowed to be at the bedsides of these patients, we took blood samples and biobanked them. That biobank served as not only a source of information not only to validate the PCR tests being developed by Ryan Sprissler at UAGC for allowing students to return to campus, but also for the work of Dr. Nikolich-Zugich and Dr. Bhattacharya to use as a reference population for their antibody studies.

We also did another study to see if people, both COVID positive and negative, who left the ICU were experiencing insomnia. That served as a very good, fertile research ground for us to try and figure out why people develop long COVID and the inflammatory markers that are associated. This led to us getting the $29M grant, which is part of a $1.18B investment from the NIH, to study long COVID. 

The fact that we were primed in these areas allowed us to really quickly pivot and segue into the current research area to address burning questions about antibodies and long COVID. We are coming up with what we think is a unifying hypothesis. When people long COVID, they develop symptoms in specific organs like the lung or brain, but we think biologically there's pathways that are responsible for how it ties in these various manifestations for long COVID into one problem. 

It's putting us in a very good situation, and that’s in part thanks to the establishment of the biobank, the IRB, and all the other resources to allow us to do these studies. The scientists can’t do it alone – we need those administrative pieces to support us. I think it's something to be said about team science and the collective teamwork of every member of UArizona. 

How do you balance the tough road of being a physician-scientist, and how does that dual career path benefit both sides of the equation?

With the time we’re in, you start thinking about meaningfulness and the meaning of existence and things of that nature. I was having a conversation with my wife trying to define how and why we exist, and what is the purpose of life – we are now empty-nesters so we have the time to actually have these discussions. 

We talked a lot about leading a purposeful life, so coming from that stance, being able to do this work, we see that as luck and a wonderful opportunity that was given to us. We know as physicians, both my wife and I, and that there are others who really don't even know about this career pathway. We are happy doing what we're doing, and we feel content and like we've been leading purposeful lives and we don't see it as a burden.

We have this job satisfaction where we take care of a patient, and the patient says, “Thank you.” We get an idea that we are able to actually implement as a research idea at the bedside and we are lucky to be able to do that. We see this job as a gift we were given. 

You’ve also founded two sleep centers here at the University of Arizona. What led you to want to assemble these teams, and what are some of your biggest milestones?

The clinical center at Banner takes care of patients with sleep disorders, and it's much needed for the community. As a faculty member of a land grant university, it's our obligation to make sure that we can also serve the needs of the institution.

Not only do we have a high burden of sleep disorders that need to be cared for by people who are academics, but we also see complex cases, and we have the capabilities to offer them unique diagnostic and therapy options. 

The research center is something that came about to fill the need for high-quality research on sleep and circadian rhythms. We have a great mass of sleep and circadian rhythm researchers here at the University of Arizona, but we were limited by not having a research center, so many years ago, I lobbied for the center. 

I thought how cool it was that we were planning on the Mars mission, but on Earth, we have a 24-hour cycle, but in space, there’s no circadian rhythm. We needed to understand exactly what the astronauts would be going through so we could help them maintain their rhythms and help prevent disease associated with impaired sleep. For that, we needed a controlled environment where we could alter night and day and study how these people would be affected with simulated conditions of Mars and space. 

It's not just relevant for space travel, but we also needed this center to understand how sleep impacts lung function in chronically ill patients, for example. Unlike other research that you can do in a dish or at the bench, we needed a facility and the infrastructural support. 

After a few long years, we were approved for the establishment of the center – it’s currently a four-bed center, but soon-to-be eight-bed research center. We will be able to not only change light timing, but also light frequency - how much on blue light versus red light. We can also administer IV medications to someone in the remote bedroom, as well as draw samples without going into their bedroom and disturbing their sleep.

We can also change the intensity of the light, and you can also change the gasses that people inhale in this place. For example, you can add a bit more CO₂ to mimic global warming. We’re working with Dr. Esther Sternberg to see how a slight increase in CO₂ affects sleep and cognition, with the idea that global warming will decrease our sleep and therefore negatively impact our brain function. 

This was thanks to a $5 million construction grant from the NIH, and it's actually only the third construction grant received by the University of Arizona in its history. The construction has started, and we are hoping the center will be open in January 2023. 

I know you’re also passionate about mentorship – can you talk a little about that?

One of our young faculty members just got a grant that allows him to be considered to transition to independence, and I was just mentioning to him I'm actually more excited about him getting a grant than a grant that I got about at the same time. When he got to his grant, it warmed my heart.

There's a unique pleasure in lighting the way for someone to be successful, and that is different from experiencing personal success, so to me that's where I draw that energy from. 

I’m also passionate about supporting underrepresented minorities in biomedical research. 

We are part of an R25 training program here which allows people to train in the area of pulmonary and sleep related breathing disorders. We are soliciting applicants to come for two weeks in the summer and winter each.

There is an opportunity for being able to tackle disease conditions and find solutions for public good by having a more diverse workforce. We know that from a clinical care delivery standpoint, people of color find more comfort and are more likely to have better outcomes that are treatment adherent if they're taken care of by physicians from their race and ethnicity. 

Similarly for our research participation, for us to be able to understand what's going on with them and for them to be more accepting of getting vaccinated during the pandemic, if they have these messages come from people that they trust, and in that sense, people being represented in our biomedical workforce, they are more likely to get vaccinated. and so the more diverse workforce that we have.

The University of Arizona has just really hit it out of the park - I think we are number one for Native Americans getting their PhDs in the nation, and I believe we're in the top 10 for Hispanics. We also have great representation of underserved minorities at the faculty and staff level in our biomedical areas, which is critical to get diverse perspectives to find solutions to diseases.

Besides the moral, ethical obligation of making sure that we are both diverse and inclusive, it's also important for the advancement of science to have a more diverse workforce, so along those lines, we are very passionate about that. We spend time on it, not just speak about it. I'm fortunate to work with a couple of other principal investigators who are passionate about that. 

That's what's great about this institution - every time we interact with someone, we learn something from them and that allows us to do better.

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