If you have Long Covid and are feeling confused by the different theories about the main mechanisms driving your ongoing symptoms, then I hope this blog will be very helpful for you. I am going to look at the top five mechanisms that have been well documented and discussed in the scientific literature. Now I am not suggesting that if you have Long Covid that all or even any of these mechanisms are definitely happening in your body, but these are the ones being most highlighted and with the best explanation for explaining the symptoms we see in Long Covid.
The other important thing to note is that each of these mechanisms will operate on a spectrum. If you just take problems with energy production in the body as an example then you may get someone feeling tired a lot of the time, you may have someone feeling completely burned out or even someone bed bound with chronic fatigue. So you can see that this will result in potentially different symptoms or different intensity of symptoms. Lastly of course you may have several of these mechanisms going on at different levels of intensity.
As you read through this blog you will begin to get the idea of how inflammation maybe an underpinning factor in all these conditions and luckily this is something that we do have a certain amount of control over through relatively simple lifestyle interventions.
So here are the tope 5 key mechanisms driving Long Covid:
· MAST Cell Activation
· Neuroinflammation & Dysautonomia
· Microvascular damage
· Metabolic dysfunction
· Mitochondrial dysfunction
MAST Cell Activation – An Immune System Response
MAST cells are a type of immune cell responsible for hypersensitivity or allergy reactions, they are present in great numbers in the gut and help keep our immune system in balance. An infection with the SARS-COV-2 virus can result in a release of a lot of cytokines, you might have heard of the cytokine storm which happens when there is a sudden and large increase in the release of cytokines, something that is more likely to happen to some people with this virus. These cytokines are chemical messengers that help to orchestrate our immune system response to an infection, and they play a significant role in generating an inflammatory response.
The ongoing release of cytokines can activate MAST cells which then breakdown and release histamine which can cause a range of symptoms including fatigue, hives, headache, and others. It is now known that around 17% of the population may have some level of MAST cell activation problem and it is often overlooked.
MAST cell activation can escalate with major physical or psychological stress, and we know that the severity of symptoms has been shown to increase after being ill with Covid-19. And people with Long Covid report a significantly higher number of symptoms that affect their activities of daily living including severe fatigue, muscle pain or tenderness, chest burning/pressure/pain, cough, sweats, loss of smell, hair loss, and loss of taste.
Neuroinflammation & Dysautonomia – Inflammation of Your Brain & Nervous System
Here I’m going to explain the involvement of the Autonomic Nervous System, that is the part of your nervous system that is not normally under your conscious control. For example it is the part that controls your breathing and heart rate. When the Autonomic Nervous System becomes out of balance it is called dysautonomia.
Long Covid symptoms possibly relating to neurological issues include fatigue, loss/change of smell, brain fog, headaches and hypoxia (oxygen shortage in body tissue). Some Long Covid patients with fatigue may exhibit a dysautonomia (imbalance of their nervous system) which might be picked up if your HRV, that is heart rate variability, is monitored. If you have a watch or Oura ring you might be able to monitor it yourself and see what helps to improve it.
The SARS-COV-2 virus may get into the central nervous system (including our brain) as it is small enough in diameter to cross the blood–brain barrier (BBB). As well as creating an infection there are also other ways that the virus could damage our brain cells (neurons) and this can lead to obstruction of the blood flow around the brain leading to hypoxia, oxygen shortage, in brain tissue.
Inflammation elsewhere in the body can result in Inflammatory molecules in our blood which can also cross into the brain and cause tissue damage. For example we know that high levels of inflammation when someone is ill with Covid-19 may drive MAST cell activation which in turn can prime our brains immune cells known as microglia to be on high alert which can sometimes lead to destruction of healthy brain tissue.
POTs (Post Orthostatic Tachycardia Syndrome) is one example of a condition thought to be caused by dysautonomia. It affects the cardiovascular system and the nervous system and can result in symptoms such as dizziness, heart palpitations, chest pain, shortness of breath and gut issues such as nausea, pain and diarrhoea. The reason it can cause gut symptoms is because our nervous system and our gut are connected and communicate with each other all of the time. It is our nervous system that controls how our gut contracts to move food through it, how it secretes mucus and enzymes and co-ordinates the blood flow to support digestion, absorption of fluid and nutrients and elimination of waste (your pee and poo!). If the normal functioning of the nervous system is disrupted it can cause excessive and uncoordinated activity and resulting in gut symptoms like diarrhoea. There is an interesting study that shows how all the long-haul COVID-19 patients in developed POTS during a tilt test (which is the gold standard test for POTS).
Vigorous inflammation in the brain can be like a chemical concussion in its severity. The brains nerve cells (neurons) drive the response of the immune system and when it goes wrong, they can destroy healthy neurons and increase the risk of autoimmunity where our immune system starts destroying our own brain tissue. This is what I mentioned earlier when the brains immune system (our microglial cells) go on high alert and start to attack our own healthy brain tissue.
There are various signals to the immune cells as to whether they should be active or not and this includes the level of inflammation, the blood flow in the brain and the type and level of neurotransmitters (chemical messengers between neurons) an they are also sensitive to our stress chemistry too, the chemical signals that get sent to our brain when we are under stress.
Microvascular Damage – Your Blood Vessel Health
So this is where the clotting problem associated with Covid-19 comes in. Blood clotting can be due to a number of mechanisms and it gets a bit too complicated to go into any indepth explanations here but these mechanisms include NETs (neutrophil extracellular traps) and Fibrinosis.
Symptoms that might be looked for to indicate a blood clotting problem can include brain fag, fatigue, hypoxia (which may in turn include anxiety, depression and inflammation) and organ damage. Obviously specialist medical intervention may be needed and if you have organ damage you will be likely under the care of a specialist medical consultant.
The type of clotting caused by NETs (neutrophil extracellular traps) is a response by the immune system to try and contain infections. In this process webs are constructed made from chromatin, microbicidal proteins, and oxidant enzymes that white blood cells release. Unfortunately this web formation can get out of control and increase inflammation (vasculitis) and cause microclotting (thrombosis).
Fibrinosis is another potential mechanism leading to clotting. This happens when there is damage to the cells lining the blood vessel which can then expose the underlying matrix and this can activate a coagulation cascade, the conversion of fibrinogen (protein involved with blood clotting) to fibrin (a strong fibrous protein which help heal wounds) which along with platelets clumping can cause clotting.
With Covid-19 as well as in those with Long Covid there potentially seems to be a problem balancing the clotting (fibrin forming) and the fibrin-dissolving pathways. When the blood vessel walls are not functioning well, this also can contribute to inflammation.
SARS CoV-2 can affects the microcirculation (capillaries) directly, causing swelling and damage of the cells lining them, and this together with the micro clotting can potential cause damage to the smooth muscle cells that are important for pumping our blood around. This of course can happen all over our body as well as in our brain. So this blood vessel damage as well as inflammation (vasculitis) may cause problems with sufficient oxygen getting to our body tissue and brain tissue which could alter things like our brain function and of course create ongoing symptoms.
Metabolic Dysfunction – Your Metabolism Is Out Of Balance
Metabolism is a term that describes the biochemical processes that allow people to grow, reproduce, repair damage, and respond to their environment, when this normal functioning gets disrupted it is known as metabolic dysfunction.
There are many direct links between COVID-19 and the metabolic (systems that use and make energy in the body) and endocrine systems (glands that secrete hormones). People with metabolic health problems e.g. obesity, hypertension, non-alcoholic fatty liver disease and diabetes, are at increased risk of metabolic dysfunction. The data shows that two-thirds of people in the UK who have fallen seriously ill with COVID-19 were overweight or obese and had a metabolic problem like high blood pressure or poor blood sugar control.
Metabolic syndrome is the medical term for the combination of diabetes, high blood pressure (hypertension) and obesity. Metabolic syndrome may be diagnosed if you have 3 or more of the following:
being very overweight or having too much fat around your waist
high triglyceride levels (fat in the blood) and low levels of HDL (the "good" cholesterol) in your blood, which can lead to atherosclerosis (where arteries become clogged with fatty substances such as cholesterol)
high blood pressure that's consistently 140/90mmHg or higher
an inability to control blood sugar levels (insulin resistance)
Metabolic syndrome is linked to impaired immune function and more severe symptoms and complications with COVID-19.
Insulin resistance is a major driver of metabolic health problems and is when the body no longer responds as normal when insulin, (the hormone that regulates blood glucose levels), is released. This has a big role to play in inflammation in the body. A vicious cycle can result, with more inflammation causing more insulin resistance in an ongoing process.
The most significant factor that determines blood glucose levels is the consumption of dietary carbohydrate, that is, refined carbs, starches and simple sugars. You will see this mentioned again in my recommendations at the end of this blog.
Mitochondrial Dysfunction – When Your Energy Has Disappeared
And finally we have mitochondrial dysfunction. Mitochondria are the powerhouses of our cells producing 90-95% of our energy and play an important role in keeping everything in our cells working well and in balance (homeostasis). Our mitochondria are tiny organelles only visible through a microscope but they are very important and in some cells make up to 40% of the cell content. Cells which require a lot of energy like heart, brain and muscle cells can have thousands of them and other cells like blood and skin cells have fewer or none.
The mitochondria are making energy when all is well, but when things start to go wrong they can switch into another mode known as the Cell Danger Response. This response to physical, chemical or biological threats aims to protect us from harm and moves mitochondria from energy production to defence mode.
Problems in mitochondrial energy production are thought to play a role in Long Covid and might be one reason for the chronic fatigue experienced by some people. COVID-19 has been found to highjack the mitochondria of immune cells and reduce the mitochondria’s ability to function and this gets worse the older we are. When the SARS-CoV-2 virus is present in mitochondria it can result in the release of mitochondrial DNA (mtDNA) into the cell resulting in an immune response and inflammation.
We know now that with chronic fatigue there can be problems in the energy production process in mitochondria where aerobic (using oxygen) processes switch over to anaerobic (without oxygen) as well as in oxidative phosphorylation, the latter part of the energy production process, where electrons are transferred to create ATP (adenosine triphosphate) our energy. With anaerobic energy production lactate is produced which can cause muscle pain, something common in both Chronic Fatigue Syndrome and Long Covid. Less energy is produced during anaerobic energy production and the mitochondria are unable to meet energy demands during exercise or acute stress giving a reason for the severe post-exertional fatigue that is commonly seen in these conditions.
Oxidative damage, as well as inflammation, can play a role here too. To understand oxidative damage the easiest example to describe is when you get sun burn or long term skin damage, like wrinkles, from the high energy molecules in the sun’s rays which attack your skin. In a similar way other high energy molecules in our environment and produced in our body can cause damage too. Mitochondria themselves produce a lot of high energy molecules, through their energy production process, which makes them vulnerable to oxidative damage. If your body does not have adequate nutrients such as vitamin E and CoQ10 then the cells struggle to help mop up these high energy molecules and this can lead to damage of the mitochondria and surrounding cell tissue.
Why Might Inflammation Be The Key?
Well by now you have probably got the idea that inflammation is a problem in Long Covid. Several of the mechanisms I have talked about potentially cause inflammation and inflammation also drives further inflammation making it a difficult process to slow down, stop and reverse. But the good news is that there are some things you can do to lower the level of inflammation generally in your body which may have a knock on effect on these processes. The aim is to try and slow it down and turn it around. I want to stress that this advice is not medical advice but lifestyle advice and that you should always seek the advice of your medical professional before making changes, especially if you are taking any medication. You may need your medication monitored and adjusted, for example if you change your diet and are on any blood sugar or blood pressure medication.
We talked about metabolic dysfunction and it might shock you to know that in the UK 1 in 4 adults are thought to have metabolic syndrome, 36% are overweight, 26% have high blood pressure, 7% have diabetes. Unfortunately many more have less than optimal levels of blood pressure and blood sugar and might be on a trajectory to be diagnosed with one of these conditions.
In the UK feeling tired all the time is one of the most common reasons (80-85%) to visit a GP surgery. This might give you an idea that mitochondrial dysfunction might be very common too.
So I believe we need to try and tackle inflammation to stand a chance at reducing the amount of dysregulation going on the body and try to bring it more into balance. So how do we do this?
Anti-Inflammatory Strategies
So now we are going to look at my top 5 recommendations for anti-inflammatory strategies that you could put into action.
1. Go Low Carb With Plenty of Healthy Fats & Protein
2. Brighten Up Your Plate With Colourful Fruit & Vegetables
3. Cut Out Processed Food & Go With Whole Foods
4. Pace Yourself Physically & Mentally
5. Find Ways To Relax Your Mind & Body
Why Should I Go Low Carb?
There are two reasons. We can use carbohydrates or fats as main fuel for our body, these two macronutrients provide the fuel source for us to make energy. You might remember the mitochondria I talked about earlier in the blog – well they help to turn these nutrients into ATP or Adenosine Triphosphate, which is the energy we run on. The mitochondria run at a high speed and we really want them to be doing this as cleanly as possible and producing as few of the high energy molecules that can cause damage and inflammation as possible. The best fuel to do this is fat and NOT carbohydrates. So this is the first reason so now lets look at the second.
Eating fewer carbohydrates is linked with improved markers of metabolic syndrome, things like insulin resistance and blood sugar control that we looked at earlier. Eating more fats and protein an fewer carbohydrates puts less stress on these systems, it results in lower blood sugar levels, more control of insulin levels and in some cases can actually reverse inflammatory conditions such as diabetes.
For more information about anti-inflammatory foods and eating to balance your blood sugar check out this blog and to understand more about your energy and what can go wrong check out this one.
So What Should I Be Eating?
You want your plate to have colour on it at every meal. Going low carb doesn’t mean no carbs at all, but it does mean that the carbs you eat should be from natural whole fruits and vegetables that are low in sugar. Good examples of these foods include blueberries, raspberries, strawberries, apples and pears, broccoli, spinach, cauliflower, lettuce, rocket, peppers, courgettes and cabbage. You want as much colour and diversity as possible as the colour pigments in these fruits and vegetables are due to phytochemicals with anti-inflammatory properties.
What To Avoid?
So you need to make sure you avoid eating inflammatory foods, especially highly processed, industrially produced foods such as biscuits, cakes, bread, cereals, crisps, chocolate bars and sweets. These foods are all inflammatory in nature and in addition to being high in carbohydrates they often contain a lot of additives which can be inflammatory too, things such as emulsifiers, colourings, preservatives, flavourings etc..
If you do need a sweet something try having a couple of pieces of 85% dark chocolate.
Pace Yourself
Now I am no longer talking about food! I am now talking about your life and how you lead it. Especially if one of your key symptoms is fatigue then you need to try and make sure you don’t overdo the amount of activities in your day that might set you back. Traditionally pacing was thought about more in terms of physical activities and particularly in relation to the symptom of post-exercise fatigue. Now we know that mental pacing can be just as important and that put yourself under too much mental or emotional stress can also be a problem.
So with physical pacing you want to try and do no more than what you could comfortably repeat the day after. This way you are trying not to over stretch your bodies capacity for making energy and coping with the physical stress on the body. With mental and emotional pacing you need to be thinking about the amount of brain power, so things like how much concentration you are using and emotional pacing might include how much time you spend dealing with emotional subjects or could relate to relationships or social situations. The key thing to be aware of is whether you are placing your body under more stress as a result of what you are doing day to day. Unfortunately our bodies reaction to stress whether it is physical, chemical, biological or mental is really just the same in terms of how it affects our nervous system and the impact it can have on other systems of the body like how we produce our energy. We used to think of stress just affecting our mind, now we know it can have a much greater physical effect on our body too. If you want to know more about how inflammation and stress are linked look at this blog.
The Art of Rest
So as I just mentioned stress can have a negative effect on our mind and body and we need to fin ways of relaxing and resting much more than we traditionally do living in our modern society. Most of us are constantly on the go whether physically or mentally, we are glued to our screens and unfortunately much of what we see results in a negative effect on our nervous system. For examples watching the news or scrolling through social media or watching a block buster film , often we go through a range of emotions from worried, angry, sad, jealous or guilty. Our brains are programmed to respond like this and can heighten the stress response in our body. The best way of countering this is to find ways of resting and relaxing that support our bodies to produce calm and happy chemical messages. So reading a relaxing book, listening to music, spending time with your cat. sitting in nature, walking at the beach, having a bath, meditating or watching a candle burn. It doesn’t matter what it is as long as it works for you. Don’t feel guilty taking this time, we all need it and you should always to look after yourself first or else you may be of no help to anyone else if you are not well. If you want to explore more about how stress and inflammation are linked then check out this blog.
I hope this blog has helped you understand some of the mechanisms that might be going on in Long Covid and how there is a strong link with inflammation. Do seek out support if you need it from someone like myself who has a special interest in Long Covid and can help you work out exactly what you need support with.
Long Covid Checklist
You can download a copy of My Personal Long Covid Checklist then please click HERE.
The checklist tells you exactly what I would do if I was suffering with Long Covid. It gives you a checklist of actions for the 6 key areas which I think are most important.
This is my starting point and it focuses on the key areas of energy production, immune and nervous system health, reducing inflammation, moving your body gently and syncing your body clock. No matter what my exact symptoms were I would go back to basics and do this first.
If you would like to book a free call with me to see how I might be able to help you then please email me on hello@moiranewiss.co.uk.
Disclaimer: Before changing your diet or lifestyle and taking any supplements always seek the advice of your doctor or another suitably qualified professional such as a nutritional therapist. The content of this blog is for informational purposes only and is not a substitute for professional medical advice. Always seek the advice of your doctor with regards to any questions you have about a medical condition.
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