A conversation with OHSU’s Dr. Aluko A. Hope, medical director at OHSU’s Long COVID-19 Program

The medical mysteries associated with Long COVID are frustrating for many. For the patients who suffer the effects of Long COVID, as well as their doctors, it has largely been a matter of managing the various symptoms, rather than the condition itself as a whole. It is also not uncommon, as U.S. Census Bureau data from 2022 show 14% of people in the United States reported having Long COVID at some point.

It’s quite difficult, however, to define Long COVID, and many experts are skeptical that it represents a unique condition. Many patients suffer lingering symptoms after any infection—regardless of the cause of the infection. Not surprisingly, many patients have also reported persistent symptoms after a bout of COVID-19, which has been dubbed “post-acute sequelae of COVID-19 (PASC),” or, more commonly, “Long COVID.” So how is Long COVID special?

Researchers have spent the last four years trying to answer that question, and some observations are worth considering. For example, some patterns have emerged when it comes to who might be more likely to experience Long COVID, and why.

Certainly, more time and research are needed. The Long COVID-19 Program at Oregon Health and Science University (OHSU) has been at the forefront of this research since it was created in March 2021, treating about 2,000 patients to date and learning valuable medical science along the way.

We asked a series of questions about Long COVID to Dr. Aluko A. Hope, the medical director of OHSU’s Long COVID-19 Program. He is also professor of medicine, Division of Pulmonary, Allergy and Critical Care at OHSU and director of OHSU’s Critical & Acute Illness Recovery Engagement (CAIRE) program.

To most people, Long COVID generally means lingering symptoms of being infected with the SARS-CoV-2 virus, ranging in severity from mild and annoying, to debilitating and life altering. What is the most current definition of Long COVID and its associated symptoms?

Dr. Hope: Long COVID is the most common umbrella term for the infection-associated chronic conditions that can emerge after a COVID-19 infection. Most of the definitions try to distinguish the acute symptoms people experience during the illness from the chronic symptoms experienced later by saying that symptoms must last at least two or three months and be either continuous, relapsing or remitting, or progressive in order to call it Long COVID.

Most commonly, Long COVID presents with multiple symptoms across multiple organ systems simultaneously. (Persistently experiencing only one symptom is less common.)

The most common Long COVID symptoms that we see in our clinic include:

• Chronic fatigue.
• Post-exertional malaise, which is when someone feels overly fatigued after minimal exertion. That exertion can be cognitive, physical, emotional or sensory.
• Orthostatic intolerance, which is a fancy term for symptoms such as dizziness, lightheadedness or feeling faint that start or continue when patients sit up or stand up.
• Sensory changes such as increased pain, balance impairment and difficulty hearing or smelling.
• “Brain fog,” which includes changes in certain mental activities such as attention, memory or the ability to get things done. It may also include changes in mental function that we can identify through psychological testing.
• Changes in sleep which can include not getting enough sleep, sleeping too much, or not feeling rested after sleep.

As we learn more, our understanding of how these conditions present and how to manage them continue to evolve and mature with time.

The Centers for Disease Control and Prevention (CDC) conducts an ongoing survey that shows females are more likely to develop Long COVID than males. It also shows the age group most likely to develop Long COVID is people in their 40s. What else do we know about those who might be more likely to develop Long COVID?

Dr. Hope: Yes, that survey is publicly accessible and can provide more insight into Long COVID prevalence and incidence by race/ethnicity, geographic location, etc. What’s clear is that Long COVID can occur across all age groups, genders, racial or ethnic groups and can occur in all socioeconomic groups. We know that the more severe the COVID-19 infection, the more likely one is to develop Long COVID. We also know that people with female sex assigned at birth appear to be at higher risk of Long COVID.

Some studies suggest that people with certain chronic conditions such as obesity or type 2 diabetes (adult onset), cancer or chronic liver disease are at higher risk of developing Long COVID. There are also some emerging studies that suggest that patients with certain connective tissue disorders such as Ehlers Danlos syndrome or hypermobility spectrum disorders (HSDs) seem to be at higher risk of chronic fatigue symptoms. (HSDs occur when people’s joints are extra “bendy” or flexible, such as being “double-jointed,” causing instability, pain or injury.)

When it comes to treating Long COVID, are physicians generally treating the individual symptoms, or are they looking at the condition more holistically, as its own syndrome, with its own therapies?

Dr. Hope: We aim to treat Long COVID holistically in collaboration with the patient’s primary care team, our rehabilitation team and other subspecialists across the OHSU community and beyond. When Long COVID presents with multiple symptoms across multiple body systems, we try to help patients and their providers think about the condition holistically. Since we still have so much to learn about these infection-associated chronic conditions like Long COVID, we think it’s important that we listen to our patients and validate their experiences.

It can be challenging for patients as well as for providers to wrap their heads around the various ways Long COVID can present itself. Even when multiple patients exhibit the same set of Long COVID symptoms, there can be differences in how we understand the significance of those symptoms in each patient. For example, Long COVID can lead to dizziness, feeling weak, headache and an inappropriately rapid heart rate when rising from a lying or sitting position (orthostatic intolerance). In some patients, these symptoms could be the body’s appropriate response to physical activity when the patient doesn’t have enough energy. In other patients, these same symptoms might be due to a short-term poor functioning of their autonomic nervous system due to stress, including the stress of the COVID-19 infection; and in yet other patients, these same symptoms might reflect a long-term imbalance in their autonomic nervous system that has been triggered by the COVID-19 infection. (The autonomic nervous system is the part of our nervous system that controls a lot of the automatic functions in our body — heart rate, blood pressure, digestion, tears and sweat production, body temperature and much more.)

So, managing a particular set of Long COVID symptoms is rarely as simple as just finding a pill for each symptom. Often, we have to spend some time coming to agreement on the factors that might be contributing to the symptoms, help the patient avoid further injury, help the patient develop skills to manage the impairments that result from the symptoms, and work collaboratively with the patient and the other members of their clinical team to diminish their symptoms and enhance their capacity. Given the state of medical knowledge, we often rely on a mix of behavioral and medication-based approaches that must be personalized to each patient.

How does being vaccinated against COVID-19 factor into Long COVID, if at all?

Dr. Hope: There are several studies suggesting that people who have been vaccinated for COVID-19 were less likely to develop Long COVID. Most of this research, however, has focused on a person’s initial COVID-19 vaccination. We need more research on the role of booster vaccinations and re-infections in the development of Long COVID.

Are there any Long COVID symptoms that may be permanent, or is it too early to say?

Dr. Hope: In general, this question assumes too much about the condition to be answerable. If somebody fell and got a concussion and developed symptoms four months after the injury, are the symptoms permanent? If someone fell and shattered their femur, are there permanent symptoms? The answer always depends on the specific patient, on treatments they chose to have, when they chose to have such treatment, what other medical and social problems are contributing to their chronic symptoms, etc.

Is there a correlation between the number of times someone gets sick with COVID-19 and Long COVID?

Dr. Hope: I don’t know of any findings that answer this specific question. We know from recently published studies that, at the population level, Long COVID is more likely after a severe COVID-19 infection which is most likely to be a person’s first COVID-19 infection, so it would not be surprising if multiple things end up being true regarding Long COVID risk and re-infections: 1) that fewer individuals get Long COVID following a reinfection and 2) that more Long COVID will develop over time due to re-infections than from the initial infection since most people will get infected multiple times.

A while back you said it’s really important for people to be their own best advocate when it comes to Long COVID – to understand their symptoms and what triggers them, for example – because in general the medical community wasn’t adequately educated when it came to Long COVID. While it’s always good for people to advocate for themselves, have providers come to understand Long COVID better?

Dr. Hope: Philosophically, I continue to believe that these infection-associated chronic conditions such as Long COVID will need patients to “flip the clinic.” Patients with these conditions should throw away the ATM-machine model of western medicine where doctors have all the medical knowledge, and patients are just expected to passively withdraw from that fountain of knowledge. Patients with these chronic conditions often need to make changes in the way they eat, breathe, move, think, socialize and work, and they must forge these changes while grappling with severe symptoms and discomfort.

I am skeptical that simply educating doctors will ever be a comprehensive solution to how we manage conditions such as Long COVID. We need to forge a health care system in which patients are better able to communicate what is going on with their bodies; a system in which patients can more easily come to understand, communicate and challenge their own health care values; a system in which doctors, patients and informal caregivers can more effectively work together to better serve the patient in their recovery journey.

What are the most exciting discoveries, or “ah-ha!” moments, regarding your long COVID research? Have you made any notable discoveries that have the potential to unlock either treatment or prevention of long COVID?

Dr. Hope: We are happy to be participating in several of the Long COVID clinical trials for RECOVER (Researching COVID to Enhance Recovery) – an initiative with the National Institutes of Health (NIH) created to find answers across many different types of research studies. The website offers a wealth of Long COVID information stemming from all participants’ research, not just OHSU. The collective is studying “the world’s most comprehensive and diverse group of Long COVID patients.”

Even without new exciting “discoveries,” I can say with confidence that repair and recovery is possible for many, if not most, patients, even if it’s not as quick or easy as we might like. And for patients who remain chronically impaired, we need to be willing to forge a world where justice and love are not only for those who can talk on Zoom for two hours, or walk for two hours, or stand for two hours, or remember what they are doing without cues, or respond to emails or texts in five minutes. Justice and love, after all, are for all people, with all levels of ability.

What Long COVID mysteries continue to challenge you and other researchers? Are there one or two that are especially significant head-scratchers?

Dr. Hope: Every patient is a head-scratcher for me. That posture of curiosity is the way I try to approach my clinical practice.

---

Participating in OHSU’s Long COVID research

At this time, OHSU’s Long COVID Program is temporarily closed to new patients. However, OHSU is currently recruiting certain patients to participate in the RECOVER clinical trials, funded by the National Institutes of Health (NIH). Specifically, OHSU is enrolling Long COVID patients experiencing sleep changes, exercise intolerance or orthostatic intolerance. Those interested in participating in this Long COVID research can send an email to longcovidresearch@ohsu.edu.