Hello friends! With the country slowly recovering from COVID-19 and an overwhelming sprint to get people vaccinated, I'd like to introduce my first article covering the pandemic. I have long avoided writing about COVID-19 because mainstream journalism has beat the topic into the ground, over-saturating the masses with spotty trends, conclusions, and politics. COVID-19 has, of course, been controversial, especially the infamous "long haul" symptoms that recovering patients experience, including brain fog, fatigue, coughing, high heart rate, and abnormal smell and taste. These sequelae have raised alarms on social media, and I want to look into these phenomena further.
I'm eager to try something a bit different when writing up on a topic like this. I think it would be fun to postulate theories behind the specific symptoms of brain fog/fatigue prior to me actually researching, and then I will reassess how close my initial theories are to what the leading science suggests are the true reasons. I'm prepared to swing-and-miss. Let's do this.
My Best Guess:
The brain fog and fatigue might be caused widespread inflammation. That's all I got, really. I've also heard of these exact symptoms being reported as long haul sequelae for people who fought infectious mononucleosis. I think there's a psycho-social dynamic contributing to these symptoms; people have been indoors, lacking stimuli from the world, possibly not eating the healthiest, etc.
Well, I gave that the good ole medical student try. Let's do some research.
What does the science say?
Dr. Anthony Fauci has suggested in the past that the feared brain fog matches well with what is known as "Myalgic encephalitis/chronic fatigue syndrome" (ME/CFS). Right off the bat, this name scares me because the run-of-the-mill medical student would likely associate "encephalitis" with a patient who is severely immunocompromised and has contracted a bug. Seeing encephalitis being characterized in a more "healthy-person" picture is enlightening and points to the fact that medical students are subjected to a learning bias when they approach new diseases. Anyways, my initial research suggests that this is still quite an unknown disease. ME/CFS, also described as "DaCosta's syndrome, effort syndrome, soldier's heart, neurasthenia, myalgic encephalitis/encephalomyelitis, Iceland disease, Akureyri disease, Royal Free disease, and chronic fatigue and immune dysfunction syndrome,"₁ is defined by the Institute of Medicine as fatigue lasting at least six months and having increased intensity at least half the time. In addition to fatigue, you may also see "post-exertional malaise, unrefreshing sleep, cognitive impairment, and orthostatic-related symptoms [dizziness and lightheadedness]."₁ There is no singular diagnostic test, and ME/CFS should be considered a diagnosis of exclusion, meaning that serious causes of such fatigue (including all things endocrine, psychological, neurological, hematological, nutritional, etc) should be ruled out and addressed prior to coming to this diagnosis.
Many people point to certain viruses as the epidemiological cause of ME/CFS, although current literature warns that no infectious cause has been proven yet.₁ Please allow me to pat myself on the back because I was spot on with the EBV association (the virus that causes infectious mononucleosis). EBV infection paints an interesting picture because it reactivates often, and patients with CFS were found to possess higher than expected titers of antibodies to the EBV antigens.₁ A couple of other viruses have been studied for an association to ME/CFS, although consistent findings are lacking.
I think it's important to note that ME/CFS is not a disease of true immune deficiency. As I alluded to earlier, these patients are not at increased risk for opportunistic infections. Some headway has been made to suggest that there may be "depressed natural killer (NK) cell function, low levels of autoantibodies (often directed at targets in the nervous system), increased numbers of activated CD8+ T cells, and increased levels of cytokines that correlate with CFS symptom severity. A widely held hypothesis is that activation of the immune system in the brain leads to production of cytokines, and that the cytokines produce the symptoms of the illness."₁
Besides from an immunology perspective, endocrine-metabolic dysfunction has been noted in many cases, including increased levels of insulin-like growth factor, decreased corticotropic-releasing hormone and decreased cortisol.₁ On the neurological/vascular perspective, the odd-ball orthostatic (position) hypotension symptoms were studied in a tilt-table test, and improvements in dizziness and lightheadedness were noted with blood pressure/cardiac drugs such as fludrocortisone, atenolol, and disopyramide.₁ It also appears that I was rolling in the right direction with the psycho-social dynamics related to this disease; depression and anxiety are believed to be consequences of this disease, although it has been difficult for scientists to ascertain what fraction of patients had clinical depression before becoming ill.₁ On the spectrum of sleep health, ME/CFS patients had "less total sleep time, lower sleep efficiency, and less rapid eye movement (REM) sleep than controls" in one study.₁ Genetically, ME/CFS patients had different levels of genes expressed relating to a major hormonal axis and the sympathetic nervous system, compared to controls.₁ Really quite interesting.
Just like Kevin O'Leary from Shark Tank is famous for yelling "show me the money" at entrepreneurs, I also like to yell something along the same lines: "show me the imaging!" (It's easier to say this because medical school has taken all my money). A study out of the Journal of Translational Medicine utilized functional MRI imaging to assess the neurological function of ME/CFS patients. Researchers found that "more extensive brain areas were recruited during cognitive tasks in patients with ME/CFS, which had not previously been well recognised. This feature may represent brain function inefficiency caused by an neurovascular coupling dysfunction."₂
So, this is an absolute crummy situation for a large group of people, especially for those who dealt with the classic COVID-19 symptoms and now have to battle this. The good news is that this disorder is getting recognized as real and serious. UpToDate suggests that doctors can address the common symptoms systematically. The associated sleep disorders can be managed with thorough assessment of sleep hygiene and medical management, specifically low dose amitriptyline prior to bedtime.₃ Pain symptoms can be managed with conservative drugs, such as NSAIDs. Depression can be managed through psychotherapy, and you guessed it, antidepressants. And dizziness/lightheartedness can be improved with the vascular drugs I mentioned previously. Curative therapy for this is wishful thinking, unfortunately. We discussed the proinflammatory cytokines, so while it would make some sense to hit ME/CFS with a cytokine receptor antagonist, like anakinra, a study showed no difference in symptomatic improvement between treatment group and controls.₃
I personally wouldn't care to start myself on medications unless absolutely necessary. As a supporter of all things exercise, I am glad to see the current literature suggesting that a formal graded exercise therapy program has been found to improve cognitive symptoms.₃ Patients can hit two birds with one stone: improved overall physical health and improved ME/CFS symptoms. How about that, eh?!
Much more research needs to be done, but a greater appreciation for ME/CFS in the medical community is a good start.
Sources:
₁ https://bit.ly/3ewQlx0
₂ https://bit.ly/32LtJ6A
₃ https://bit.ly/3dNB0cr
At the time of creating this blog article, I am a medical student. This is not medical advice. I graciously accept donations towards website hosting costs to my Venmo @Ezra-Guttmann
תגובות