COMMENTARY

Long COVID Is Frustrating. That Doesn't Mean We Should Lose Hope

E. Wesley Ely, MD, MPH

Disclosures

August 08, 2022

Let's face it: Long COVID is frustrating, not only for the patients who are suffering but also the families suffering alongside them. It is also frustrating for healthcare professionals who are still looking for a better understanding of this mysterious syndrome.

I would like to make three points to help put this frustration in context.

Long COVID is complicated. Patients with long COVID have described more than 200 symptoms that they experience for months or even years after acute SARS-CoV-2 infection. It is clear to them that this viral infection has endangered their livelihoods and personal well-being. Yet we can offer patients no outright cures.

Worse, I'm sure that as a physician, I have at times seemed upset and perhaps sent the message to my patients that they are a burden to me. If I have, I am sorry. It's in no small part because I'm grappling for answers, just like they are.

I remind myself that these patients are not difficult. The situation is difficult. My patients are simply opening up about the ways in which they are suffering. Just because I don't have a scientific explanation for all that they are experiencing does not diminish the veracity of their complaints. Patients who attend our Critical Illness, Brain Dysfunction, and Survivorship (CIBS) Center long COVID support group tell us that even "mild" COVID has left them disabled and unable to work, care for families, or complete tasks in their job and daily life.

When I communicate with patients living with long COVID, I work to temper and channel my response: "I want to admit to you that I do not understand what is wrong with you. However, I believe you. You are the expert of your own illness, and even if I don't offer you a cure or remedy today, I want to assure you that I will not leave you; that I will stick with you in the months and years ahead as we gain more scientific information with which we may prescribe the right treatment."

Early COVID neuroscience was incomplete. The earliest autopsy studies of patients with COVID-19 showed a lack of viral presence in the neurons themselves. This led us to believe that the brain was not involved and allowed us to dismiss the patient's complaints as potentially psychosomatic. Now, there is a growing body of evidence that tells a different story, including the UK Biobank MRI study of 401 patients (mostly nonhospitalized with mild COVID) showing an overall reduction in global brain size over time compared with 384 controls. Specific findings included changes in gray matter thickness and tissue contrast in several parts of the brain — the orbitofrontal cortex, parahippocampal gyrus, and olfactory cortex. Other neuroimaging and cognitive testing data support abnormalities in regions of the brain, like the hippocampus and frontal cortex, that help explain the profound anxiety, memory loss, and neurocognitive deficits among patients with long COVID.

In addition, there are now excellent data from the basic sciences documenting that the virus infects not only endothelial cells but also astrocytes, both of which indirectly will affect the longevity and overall health of our neurons. Glial cells are essentially the glue that holds the brain together and provide the environment for neurons to thrive. When glial cells are activated by COVID infection, they create inflammation, which in turn sets in motion a pathway toward overall brain atrophy, long-term cognitive disability, and mental health disorders.

We have solid data across mammals (eg, humans and mice) that COVID causes increases in neurotoxins and neuronal cell death similar to that seen in the brains of patients with cancer after receiving chemotherapy. The neuropsychological testing we are doing as part of our ongoing National Institutes of Health (NIH)–sponsored investigations indicates that many of our patients with long COVID essentially have deficits commensurate with an acquired dementia.

The takeaway for me is that there are data to support the complaints we are hearing from millions of patients with long COVID. I feel compelled to validate them, so they don't think they're going crazy. The benefit to those with long COVID of being heard by medical professionals cannot be overstated, and I will gladly be an instrument in this important aspect of the healing that needs to happen in their lives.

Neither patients nor healthcare professionals should lose hope. At times in this pandemic, it has been easy to feel hopeless. Now, with many COVID survivors still struggling long after the virus is gone from their bodies, too many people are losing hope. A study of 150,000 COVID survivors, both hospitalized and not, showed they had a 10-15 times higher risk of considering suicide at 1 year compared with 11 million control patients.

If I've learned anything over the past 20 years of studying long-term outcomes after critical illness, it is that rapid-onset neural injury is also highly likely to be at least partially correctable.

When patients acquire a brain injury from the post–intensive care syndrome after sepsis or other forms of critical illness, many of them benefit from brain exercises even years after their initial injury. We have exciting data being generated in current NIH- and US Department of Veterans Affairs–sponsored clinical trials of cognitive rehabilitation for both COVID and non-COVID ICU survivors.

Although the intensity of the postviral syndrome, long COVID, seems "on steroids" compared with prior postviral illnesses, I believe that every patient should still have some faith in the power of the brain. Neuroplasticity can still be harnessed. If your patients love math, they can do Sudoku. Those who love words can spend more time on crosswords or playing Scrabble and Wordle.

There are online games as well; I won't endorse any specific examples, but the brain wants exercise. If a patient's arm atrophied while in a cast, they'd be advised to lift weights. Patients can be encouraged to find their preferred way to "lift weights" with their brains. Doctors, nurses, and therapists, consider speaking with your patients and explore how to help them learn to do this themselves.

Some of my patients have found great benefit from self-regulated 12-week prescriptions of brain games. None of us can promise benefits for everyone, and we are still early in our understanding, but this is not a reason to be hesitant. We are in the infancy of the science specific to long COVID, but we are building on decades of neuroscience from other forms of acquired dementia and cognitive impairment.

Patients, more than anything, should be reminded of this: Do not lose hope. The brain is robust and flexible in its neuroplasticity.

To all those serving patients with long COVID as they go through this difficult time, let's help each other harness the power of empathy and compassion to enhance patients' recovery.

E. Wesley Ely, MD, MPH, is a professor of medicine and critical care at Vanderbilt University. He is co-director of the Critical Illness, Brain Dysfunction, and Survivorship Center at www.icudelirium.org and the author of Every Deep-Drawn Breath: A Critical Care Doctor on Healing, Recovery, and Transforming Medicine in the ICU. He can be found on Twitter and TikTok at @WesElyMD.

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