The science behind Long COVID is understandably evolving. The majority of the literature falls into three categories. 

1. Examining the patients with biopsies, lumbar punctures, scans, and electrophysiologic studies in very small select groups of patients. 

2. Following patterns of symptom progression in larger populations, identifying which symptoms are common, and which go together.

3. Looking at treatments (medications or other therapies) often given for other reasons and how they affect risk and progression. 

Because of how new the science is for Long COVID, it isn’t surprising that there is little data on specific drugs or treatments in the classic double blind placebo controlled setting. However, the results of the current literature have found that Long COVID isn’t so new after all. 

The results of the biopsies and other testing, the patterns of symptom progression, and the treatment effects seem to perfectly (or near perfectly) mirror two prior conditions that have a lot more data on effective interventions. The older and more accepted diagnosis that is very similar to Long COVID is ME/CFS which occurs in patients after recovering from infectious Mono (the epstein barr virus). The other, still quite controversial in academic circles, is typically called Chronic Lyme. This is extraordinarily helpful with finding possible treatments because to the extent that Long COVID is similar to ME/CFS, the treatments seem to be similarly effective. 

When we talk about testing, there are two main categories. There are tests that we run on patients to help make a diagnosis or to make decisions about treatment, and there are tests that are only relevant in research because they don’t seem to help make decisions about how to treat the patient. It is very frustrating for patients, but most of the clinically relevant testing in Long COVID (as well as ME/CFS) is looking for other conditions that could be contributing to symptoms. Regular brain MRIs don’t show changes in most patients because there isn’t a lot of large structural damage to the brain. An MRI can look for other conditions like strokes or prior inflammation, but they don’t show the brain fog or fatigue. Very high strength MRIs, or other scans that look for changes to brain energy use are showing some changes in Long COVID patients, but since they are very expensive and don’t guide treatment they aren’t run outside of research trials. 

The immune system is clearly playing a major role, though it's pretty complex. There are a few “categories” of immune system troubles, and the testing for them is looking for antibodies that attack the patient instead of the infections like they are supposed to. There are also chemicals we can test for called “cytokines” that are dysregulated in certain autoimmune syndromes. Lastly, there are symptoms that really only happen when the immune system is acting out, like fever, flushing, and certain rashes. All of these tests can be abnormal in Long COVID and ME/CFS, but not in a way that helps us to treat the patients. They sometimes do identify other autoimmune conditions like Rheumatoid Arthritis, Sjogren’s, and others, but the main abnormal cytokines aren’t tested for clinically because they don’t change an individual patient’s diagnosis or help make treatment decisions.  

Muscle testing is also abnormal in ME/CFS patients. Certain measurements of the electrical activity in the muscle have been shown to be altered in small groups of Long COVID patients in a nearly identical way that they change in ME/CFS. Biopsies using very specific types of microscopes like those fancy electron microscopes, or looking for tiny changes to blood vessels, similarly show changes when you compare healthy controls to Long COVID patients. However, there are some symptomatic people with normal appearing biopsies, and some healthy people who have some of those changes. We call this limited sensitivity and specificity. That makes these tests very valuable in identifying that the problem is “real” and that something is happening to these patients, but the only real test that helps diagnose Long COVID is a physician taking a good history and doing a proper physical exam. 

Now this isn’t the end of the story. While we don’t need a test to diagnose the POTS syndrome, a tilt table test and a skin biopsy to look at the nerve fibers are done to support the diagnosis. Sleep studies are often helpful in making sure that the fatigue isn’t (at least in part) due to sleep apnea. Testing of the heart’s electrical activity and specific scans can look for evidence of inflammation in or around the heart in some people. Lung doctors can test to see if Asthma or COPD are part of the shortness of breath that many patients experience. However, these aren’t really looking for Long COVID, and having sleep apnea doesn’t mean a patient doesn’t also have Long COVID. 

So if Long COVID doesn’t have a blood test, then how is it diagnosed? It’s pretty simple. First, there has to be some evidence that a person likely had COVID-19, and that the immediate infection period has passed. Some of the same symptoms of fatigue, migraine, and shortness of breath can be part of the active infection. If they occur in the weeks following the infection, it could be a different syndrome called “post-acute sequelae of COVID” that resolves for the majority of patients. However, at 3 months after the infection, most of the other problems will have stabilized and the likely diagnosis is Long COVID. 

While there are no formal criteria for the diagnosis of Long COVID, I am sure many people are planning committee meetings to make one. In the meantime, the classic symptoms occurring after infection are 

1. Brain fog and other cognitive complaints

2. Mental and physical fatigue

3. Migraine

4. Insomnia or excessive sleep requirements

5. Muscle type pain (aching, throbbing) and nerve type pain (burning or zapping)

6. Shortness of breath with minimal exertion

7. Fast heart rate, or at least feeling of palpitation, with minimal exertion

8. Dizziness and perceptual disturbances

9. Depression and Anxiety

Obviously there can be other symptoms, and many of the above symptoms go together. Most of the dizziness is either related to the light headedness in POTS or the sensory processing disturbances in Migraine. When the all powerful committees meet, they may leave off a few of those symptoms or add some more. I suspect you will need to fulfill 3 criteria. They love that. 

The population data seems pretty consistent from group to group, and luckily, unlike chronic lyme, there isn’t too much debate about how real Long COVID is. However, it will be a long time until there is enough data on Long COVID for us to use it to guide treatment. For now, we will need to use the data on treatment of ME/CFS. Most of that is treatment of the component symptoms and working on global measures of health (diet, exercise, etc…). While this may seem like it is treating “the symptom and not the problem” that isn’t entirely true. Many symptoms of Long COVID create a vicious cycle that worsens the syndrome over time if untreated. 

It is really hard to work on breathing techniques when you have a severe migraine. It is hard to treat a migraine if you have severe insomnia. It is very difficult to exercise with the POTS syndrome and muscle pain. Without exercise, you can’t improve stamina, treat fatigue, and regulate your sleep cycle. While medications don’t “fix the cause” of Long COVID, they can stop this vicious cycle and put patients onto a helpful cycle. The migraine is a bit better so they can be more active during the day. That helps their sleep quality, which helps their migraine in turn. Lastly, those global health measures I talked about (sleep, diet, exercise) do have a huge impact on the immune system functions that are abnormal in Long COVID. Many (including this author) believe they are the most important treatments in Long COVID, though there are many other options as well. To discuss your symptoms, request a consult today.