Long Covid And Chronic Illnesses


I've noticed an overlap between the symptoms of "Long Covid" and chronic illnesses such as Fibromyalgia, Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) [CFS/ME], Systemic Lupus Erythematosus (SLE).

The common symptoms may tie in with a low-level of background inflammation also seen in obesity, which may explain the link between the severity of acute Covid symptoms and obesity. Finally, I speculate that there may also be a link between background inflammation and mental health.


What Is "Long Covid"?

For some people, infection with the virus SARS-CoV-2 causes COVID-19 symptoms for weeks or months after the acute phase of the infection has ended. For the first 12 weeks this is called, "Ongoing symptomatic COVID". After 12 weeks it's called "Long Covid" or "post-COVID syndrome".

Long Covid And Chronic Illnesses

Many people recover from COVID-19 infection within a few days or weeks. However, many people report one or more post-infection symptoms lasting for months. The severity of "Long Covid" symptoms do not appear to be related to how badly you were affected by the initial infection with COVID-19.



There are many different symptoms of Long Covid. Some of the symptoms are...

Respiratory & Cardiovascular symptoms
Chest tightness
Chest pain
Generalised symptoms
Neurological symptoms
Cognitive impairment (‘brain fog’, loss of concentration or memory issues)
Sleep disturbance
Pins and needles or numbness
Delirium (in older people)
Gastrointestinal symptoms (digestive system)
Abdominal pain
Anorexia and reduced appetite (in older people)
Weight loss
Musculoskeletal symptoms
Joint pain
Muscle pain
Psychological/psychiatric symptoms
Symptoms of depression
Symptoms of anxiety
Ear, nose and throat symptoms
Sore throat
Loss of taste and/or smell
Dermatological symptoms
Skin rashes

(source: UK NHS)

Note, if you think you may have COVID-19, contact NHS 111 for help and advice.

How Does Long Covid Relate To Chronic Illness?

The symptoms of Long Covid are similar in many respects to those reported by people suffering from chronic illness.

Long Covid And Fibromyalgia Syndrome (FMS)

People with Fibromyalgia report chronic, systemic pain and fatigue as well as "fibro fog" which is a cognitive impairment. While the body is hypersensitive to pain, there's currently no biological mechanistic explanation for it.

However, a very recent study led by King's College London, has shown that many of the symptoms of fibromyalgia are caused by antibodies increasing the sensitivity of pain-sensing neurons. This brand new research shows that fibromyalgia is a disease of the immune system, rather than the model of previous work which suggested that it was due to differences of neurotransmitters in the brain.

When antibodies from humans were injected into mice, the mice developed fibromyalgia-like sensitivities to pressure and cold and also moved less (perhaps analogous to fatigue in humans). Mice injected with antibodies from healthy adult humans did not show the same symptoms. Furthermore, antibodies from people living with fibromyalgia in the UK or Sweden produced the same results. It was only the IgG fraction of the blood which generated the physical changes. The IgG antibodies from fibromyalgia patients bound...

"to satellite glial cells and neurons in vivo and in vitro, as well as myelinated fiber tracts and a small number of macrophages and endothelial cells in mouse dorsal root ganglia, but no cells in the spinal cord".

Mice injected with the fibromyalgia antibodies recovered after a few weeks, when the antibodies had been cleared from their system, which strongly indicates that any therapy which neutralises the antibodies in humans may be an effective treatment.

Under "Generalised Symptoms" of Long Covid, listed above, "Fatigue" and "Pain" are both listed and "Cognitive Impairment (brain fog)" is listed under "Neurological Symptoms".

Long Covid And Lupus (Systemic Lupus Erythematosus (SLE))

People with Lupus (SLE, Systemic Lupus Erythematosus) also report "Fatigue" as well as "Headaches, confusion and memory loss". However, Lupus is an auto-immune disease with a known increase in auto-antibodies, which means a test can differentiate it from Fibromyalgia.

Symptoms of Lupus not common in Fibromyalgia are: a butterfly-shaped rash on the face, fever, swelling of joints along with joint pain or tenderness, shortness of breath, chest pain and skin lesions that appear or get worse with sun-exposure.

Again, we can note that symptoms overlap with Long Covid such as the fatigue, confusion, memory loss, chest pain, headaches, joint pain.

Interestingly, Lupus symptoms can range from mild to severe. Milder cases produce joint and skin problems and tiredness. Moderate and severe symptoms are a result of increasing inflammatory damage to internal organs such as the heart, lungs, brain or kidneys. The severest symptoms can be life-threatening.

The severest symptoms of Lupus are reminiscent of the "cytokine storm" seen in the worst affected COVID-19 cases.

Lupus sufferers will be familiar with the "flare-ups" (relapses) and remission states of the condition. Why this happens is unknown, but triggers can be as disparate as anything which causes emotional or physical stress.

For a full Lupus review, see here. What appears to happen is that immune cells which normally "eat" dying cells (phagocytes) don't do their job properly, which results in dying cells (apoptotic cells) not being cleared from the body normally. These apoptotic cells then display parts of themselves at their cell surface. The parts are not normally displayed by healthy or dying/dead cells. The inappropriate display activates the immune system via T-cells which results in the release of cytokines, inflammation and stimulation of B-cells which generate IgG auto-antibodies. The auto-antibodies bind to apoptotic cells, forming immune complexes and inflammatory reactions which cause tissue damage. It's the auto-antibodies which can be tested for and confirm a Lupus diagnosis.

Long Covid And Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) [CFS/ME]

The symptoms of Chronic Fatigue Syndrome (CFS/ME) are mainly a feeling of extreme tiredness (fatigue, as the name of the syndrome suggests), as well as sleep problems, muscle or joint pain, a sore throat or sore glands which aren't swollen, problems thinking, remembering or concentrating, flu-like symptoms, feeling dizzy or sick and a fast or irregular heartbeat (NHS: CFS/ME).

As we can see, there's again significant overlap between the symptoms of CFS/ME and Long Covid. The fatigue is obviously the major similarity, but again there's muscle or joint pain, sore throat, sleep disturbances, nausea and cognitive issues. Again, it appears that Long Covid and CFS/ME, like Fibromyalgia and Lupus, have many symptoms in common, which again points to a systemic low-grade inflammation as a probably cause.

The BBC has a video on ME and Long Covid's overlapping symptoms…

Long Covid Gender Differences

Women are at much higher risk of developing Fibromyalgia (90% of sufferers), Lupus (90% of sufferers) and CFS/ME (60-65% of sufferers). It would be interesting to know what percentage of Long Covid sufferers were male and what percentage were female.

According to an article in the Guardian, "women who get long Covid outnumber men by as much as four to one". I would consider that to be strong circumstantial evidence to support my hypothesis that long Covid is another chronic illness which women are more likely to get than men due to hormonal differences which make them more prone to low-level background inflammation.

One theory for women being more prone to chronic auto-immune diseases such as Long Covid is that hormonal changes, particularly related to pregnancy, may increase susceptibility. The mother's immune system must prevent its own rejection of the developing foetus to prevent miscarriage. It's possible that this dampening of the immune response may make auto-immune conditions more likely.

Inflammation And Diet

In a recent article I looked at obesity and why the low-level background inflammation associated with adipose tissue may have made obese individuals more susceptible to COVID-19.

It could also be the case that what we eat and drink may cause inflammation directly, distinct from the cytokines released from fat stores. For example, this scientific study says this about alcohol...

"Specifically, alcohol and its metabolites promote intestinal inflammation through multiple pathways. That inflammatory response, in turn, exacerbates alcohol-induced organ damage, creating a vicious cycle and leading to additional deleterious effects of alcohol both locally and systemically. "

Do people know that drinking alcohol causes direct damage to their organs and indirect damage through triggering direct gut inflammation AND the calories in alcohol increasing their chances of being overweight or obese and the inflammation triggered by that? If they did, would they drink less? I think it's fair to say they would.

A meta-review (which looks at many previously published scientific studies to try to get a clear understanding of a situation) published in 2020 showed very strongly that an inflammation biomarker (CRP, C-reactive protein) was reduced in vegans compared to omnivores. The significance was p < 0.0001, which equates to a 1 in 10,000 chance that the result was due to randomness. A scientific study generally needs a "p" value of < 0.05 to be considered significant, which is equivalent to a 1 in 20 chance of randomness. The results of comparing vegetarians with omnivores produced that exact number, p = 0.05, which is therefore on the border of significance.

However, as the authors point out, none of the other biomarkers of inflammation showed significant differences (interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1 receptor antagonist (IL-1 RA), tumor necrosis factor-alpha (TNF-ɑ), E-selectin, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), adiponectin, omentin-1 and resistin.) The authors stated that this may be due to most inflammatory biomarkers only being investigated in "single studies so far".

Inflammation And Gut Bacteria

Interestingly, bacteria in the gut produce various short chain fatty acids (SCFA's) by fermentation of fiber. The more fiber you eat, the more SCFA's are produced. The fatty acids such as acetate, propionate and butyrate are known to directly affect the immune system of the human host at multiple locations by passing into the bloodstream.

"Insufficient intake of “healthy foodstuffs” adversely affects the production of bacterial metabolites. These metabolites and those derived directly from food drive beneficial downstream effects on immune pathways. We propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of inflammatory disorders in Western countries.

It therefore appears that the effect of diet on the inflammatory response and background activity levels can either be harmful due to cytokine release from adipose tissue, or beneficial through SCFA's released by gut bacteria as long as they have sufficient fiber to ferment.

Long Covid, Inflammation And Mental Health

The UK Office of National Statistics released a report in July 2021 which stated...

Three in ten adults (30%) with long COVID reported experiencing moderate to severe depressive symptoms in the last 2 weeks compared with 16% of those who have not had coronavirus (COVID-19) 
Of those who have experienced long COVID, a quarter (25%) were likely to have some form of anxiety compared with 15% of those without COVID-19. 

While this kind of analysis can't prove that Long Covid was responsible for the increased rates of depression and anxiety, it is a strong indicator, especially when the rates are nearly double that of people who hadn't had COVID-19.

But why would COVID-19 cause depression and anxiety?

Low-level background inflammation associated with adipose tissue may have made obese individuals more susceptible to COVID-19. It may also lead to mental health issues. It seems that on-going background inflammation may contribute to depression, anxiety and other mental health conditions because the pro-inflammatory cytokines associated with inflammation can cross the blood-brain barrier and affect the brain.

Specifically, cytokines can interfere with the serotonin levels, by activating IDO, which degrades both tryptophan and serotonin, which may decrease the amount of serotonin in the brain and depress mood.

"Proinflammatory cytokines such as interleukin-2, interferon-γ, or tumor necrosis factor-α activate the tryptophan- and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO)."

A common class of anti-depressants are SSRI's (selective serotonin uptake inhibitors) which keep serotonin active in the brain for longer.

Genetic variation in the serotonin transporter gene, which encodes for the serotonin transporter molecule, which transports serotonin back into the pre-synaptic neurone, has been associated with anxiety...

"Studies have shown a small, but significant, increase in anxiety in both infants and adults that carry a variant of the serotonin transporter (5-HTT) gene, indicating that 5-HTT influences anxiety-related behaviour."

... and in mice, genetic mutations in the serotonin receptor have been associated with anxiety...

"Anxiety-related behaviour is altered in mice bearing mutations in specific genes, including 5-HT1A."

Few studies have been done looking at Long Covid and mental health, but a meta study done on outbreaks of previous coronaviruses SARS and MERS showed that 32% of people suffered from PTSD post-illness, 15% from depression and 15% from anxiety. A study on Long Covid showed that:

"In patients with no previous psychiatric history, a diagnosis of COVID-19 was associated with increased incidence or a first psychiatric diagnosis in the following 14 to 90 days compared with six other health events. "
"In this study the incidence of any psychiatric diagnosis in the 14 to 90 days after COVID-19 diagnosis was 18%."

One would expect a psychiatric illness to develop over time. It will be interesting to see the follow-up data for people suffering extended Long Covid and its effect on their mental health.

Latest Long Covid News

Vaccinated People Who Catch Covid Are Less Likely To Get Long Covid

Data gathered from the Zoe Self-Reporting Covid app and published in The Lancet has shown that people who are vaccinated against Covid are less likely to get Long Covid. In the people who got Covid despite having two vaccine shots, the odds of getting Long Covid were halved (5.2% vs 10.7% for unvaccinated controls).

Long Covid In Children And Young Adults Not As Common As Feared.

Long Covid in children is not as common as some people had feared, leading child health experts have said, based on an unpublished large survey:

After the world's biggest study into the issue, the researchers, led by University College London, said they were "reassured".
They surveyed 11- to 17-year-olds testing positive for coronavirus in England between September and March.
The research suggests somewhere between 2% and 14% still had symptoms caused by Covid 15 weeks later. (BBC source) 

Long Covid Is Not As Common As Feared In Adults

Along with the findings for children and young adults (see above), a study by the ONS has shown that long COVID isn't as common as thought in the general population.

Instead of one person in ten suffering symptoms beyond three months, it appears to be more like one in forty. Three percent of people experienced continuous symptoms for 12 weeks, compared to just 0.5% of controls.

Interestingly, they say that...

"Irrespective of the approach to measurement, post-acute symptom prevalence was highest in females, adults aged 50 to 69 years, people with a pre-existing health condition, and those with signs of high viral load at the time of infection."

It may not be a coincidence that middle-aged females would also appear to be most susceptible to chronic illnesses which may have made them more likely to get long COVID.

Neil Shearing, Ph.D.