“But my hurt soon moved to anger as I ruminated on the fact that it is long haulers like me, who have so little reserve energy left to give, who have been doing the heavy lifting to get the message out.”
- Tracy Kurtzer, MD, obstetrician & gynecologist, Northwestern University
“If you encounter [patients with long Covid], remember that they are suffering. Remember that they don’t want to be pitied. . .and they don’t need to be told to do more or less or to approach things differently. Be gentle. Disease eventually ensnares us all; when it happens to you, you’ll crave the same.”
- Jennifer Senior, staff writer, The Atlantic
Well after their initial COVID-19 infection, an estimated 16 million Americans continue to suffer from the puzzling, often disabling illness called “post-acute sequelae of COVID-19 (PASC)” or, simply, “long Covid.” Although much remains unknown about this disease, considerable progress is being made on two fronts: understanding the pathogenesis of the illness; and finding an effective treatment. Today I focus on these advances.
Defining “long Covid.” Before embarking on the main topic of this post—progress in understanding and treatment of the illness—we need to know what we mean by “long Covid.” There is yet to be a universally accepted “case definition” of the disease. Nonetheless, most experts agree that two elements must be met for the diagnosis: (1) evidence of a recent SARS-CoV-2 infection; and (2) an otherwise unexplained fatigue that persists for at least 3 months after the initial (acute) infection.
What causes long Covid? No one knows what causes long Covid. What we do know is its etiology, that is, the disease is triggered by a specific virus, namely, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We also know that many of the clinical features of long Covid are shared by another equally debilitating and puzzling illness called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). (See my August 5, 2020, Germ Gems post, “Post-COVID-19 Fatigue: the New Chronic Fatigue Syndrome?”)
As is the case for patients with ME/CFS, patients who are suffering from long Covid experience a sense of exhaustion that is made markedly worse by relatively minor physical exertion. They’re also routinely plagued by unrefreshing sleep as well as trouble concentrating and impaired memory. (The neurocognitive symptoms of long Covid are often referred to as “brain fog.”) Like the initial infection (acute COVID-19), long Covid is a multisystem disorder. In addition to the brain, the illness can involve the lungs, heart, gastrointestinal tract, and in all cases, a dysregulated immune system.
Pathogenic mechanisms of long Covid? In the article “At the Root of 3 ‘Long’ Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome,” in the June 2022 issue of Neuroscience Insights, University of Minnesota neuroscientists Lisa James and Apostolos Georgopoulos provided what I consider a breakthrough in thinking about the pathogenesis of long Covid. These researchers proposed what they called “the persistent antigen hypothesis,” and they backed up their hypothesis with scientific data. (See my September 7, 2022, Germ Gems post, “Long Covid: Older Adults at Risk” for more discussion.) Since then, several other research groups have published studies supporting the “persistent antigen hypothesis” of long Covid.
The key concept underlying this hypothesis is that some patients who become infected with certain kinds of pathogens (in particular, viruses and bacteria, or components of these pathogens called “antigens”) have an immune system that is unable to clear the body of this microbial material. Instead, the pathogens/antigens persist and continue to cause damage. If the ongoing damage is to the brain, for example, a condition called “neuro-PASC” develops.
Treatment and prevention. The rationale behind the search for understanding the pathogenesis of long Covid is to discover effective treatment and prevention strategies. The most convincing evidence of therapeutic benefit for long Covid emerged from a recent randomized clinical trial of cognitive behavioral therapy (CBT) in The Netherlands. (The results of this study were published in Clinical Infectious Diseases in May 2023.) CBT is a form of talk therapy aimed at changing the way a patient thinks or behaves. It has proved useful for a variety of mental and physical health problems.
In the study from the Netherlands, the researchers showed that patients that received CBT “were significantly less severely fatigued across follow-up assessments than patients receiving CAU (care as usual).” Secondary outcomes in the study also favored CBT. These were physical and social functioning, somatic symptoms, such as pain and weakness, and neurocognitive symptoms.
In several small studies, researchers also tested a growing number of other treatment modalities. These include antiviral drugs (Paxlovid and molnupiravir), a diabetes drug (metformin), a cellular bioenergetics compound, AXA1125 (studied at Oxford University), psychedelic drugs, and hyperbaric oxygen. Several of these agents appear promising, but it’s too soon to know.
The list of agents that may be useful in prevention of long Covid is much shorter than that of potential treatments. Early antiviral treatment of acute COVID-19 appears beneficial. And COVID-19 vaccines prevent not only acute infection but also development of long Covid.
What should you do if you think you have long Covid? Patients with long Covid are desperate to feel better and, like many ME/CFS patients, are often willing to try anything. Unfortunately, there is no quick fix for this illness. And, while there are charlatans out there promoting numerous false claims and fake cures for long Covid, some of these claimed “cures” can be harmful. (See “Snake Oil” Fake Cures for Long COVID Leave Patients at Risk” WebMD, August 2023). Anyone with long Covid should be wary of such claims.
What all patients with long Covid do need, however, is a good primary care doctor (an internist or family physician). Good primary care doctors can make the diagnosis of long Covid, and, when deemed appropriate, refer patients to clinics specializing in the care of long Covid patients. (See, Science News, “Where are the long COVID clinics?” November 2022.) The crucial instrument that these caregivers possess is a pair of ears, that is, they listen empathetically; they practice the “art of medicine.”
It is also important for patients with long Covid to know that many of the health outcomes of the disease can resolve on their own over time. The course may be long but don’t give up! As I conveyed in Rule 9 in my book “Get Inside Your Doctor’s Head,” Timing is everything. And sometimes, time is the cure.
