By Liv E. Helmfrid

Does it feel like your cells are tired?

There is some research showing that post COVID is very much physical – and not something you get from “worrying too much about your health”, or some other dismissive nonsense. I’m sorry if that’s what you’ve been told.

Researchers had people with post exertion malaise due to long COVID do a workout. They studied how the muscle cells were affected by the activity and found that they worked poorly after the workout in several ways. Exactly how is written in their report: “Muscle abnormalities worsen after post-exertional malaise in long COVID” 

So, no wonder it feels like something is wrong – it is! This is one of many research findings indicating that what I and many other patients are commonly told – that  post COVID is caused by a  “dysregulated nervous system” – is just not true.

Why me…

Data suggests that the longer it takes for the body to get rid of the virus from an acute COVID infection the more likely it is to get long COVID. 

“Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection”

This may mean that long COVID can be prevented (or at least the risk reduced) by helping the body clear out the virus faster. Trials suggest that people treated with Metformin, which has antiviral properties, during the first five days after getting infected with acute COVID were 40% less likely to get long COVID. “Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up | medRxiv”

This connection between clearance time and risk of long COVID should, one might conclude, mean that helping the immune system to be efficient is good. I also personally think it may actually help when you already have long COVID. Those things could be vitamin D as well as other vitamins and minerals, not eating things your immune system reacts to, taking care of your other medical conditions, medications and your menstrual cycle, sleep, and some kind of peace and quiet. 

Talking about vitamins and minerals, there are a few things that are good to know:

A) The way blood tests are evaluated is through a set of values called reference intervals. The reference interval for a given test is based on the results that are seen in 95% of the healthy population. Clear signs of deficiency can be present even if the value is inside the reference interval because of how they are constructed. The optimal interval can be much more narrow, and it’s possible to experience symptoms of deficiency even inside some of the reference intervals. 

B) Nutrient Reference Value (NRV) is the statistically proven minimum recommended daily intake to prevent serious diseases such as scurvy, in 97.5% of the healthy population. Supplement companies often have many times the NRV in their products in order to promote health. Look up the toxic dose of the substance and compare it with NRV.

C) It really helps general health to have optimal levels of vitamins and minerals. And suboptimal levels are common.

The vaccine against COVID also prevents long COVID, and not just because of the obvious prevention of getting it in the first place. I’ve also found some research suggesting that it reduces risk of long COVID even if infected. “Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis”

I clearly have some symptoms of long COVID but a long way from all of them, does that mean I don’t have it?

Researchers have looked at data from a lot of patients suffering from post COVID. They found a pattern of symptoms and identified four different categories of patients with problems in different parts of the body:

Type 1: cardiac and renal systems (heart, kidney and circulatory problems) – mostly older people that had severe COVID

Type 2: respiratory (breathing), sleep-problems and anxiety

Type 3: musculoskeletal (muscle pain, connective tissue disorders etc.) and nervous system (blood pressure, thinking etc.)  – this is the category that had most autoimmune diseases. It’s unclear to me if “nervous system” includes POTS (postural orthostatic tachycardia syndrome – postural tachycardia syndrome — read on for more information).

Type 4: digestive and respiratory systems.

“Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes – PMC”

Here is a beautiful graph of the types in more detail:

“ Incidence rates of potential PASC conditions in each subphenotype”

But why, what, how, why? 

There are different teams researching different “parts” of the disease. As of now I find it a bit hard to work out the puzzle of how they relate to each other. But my feeling is they somehow do. I really hope the teams talk to each other! Here are a few different things I found:

Virus bits

There is a theory that long COVID is caused by small bits of virus that are still in the body after the acute infection is over. Researchers are testing an antiviral drug, Paxlovid, to see if it makes the bits of virus go away and thereby long COVID itself – hopefully. The results should be out some time this year. 

 “Pfizer’s Paxlovid is being tested against post-COVID in a major Swedish study”

Abzymes

Antibodies are made by the body after an infection to recognise pathogens, and they are the reason why you don’t get the same infection twice (unless the virus mutates). It seems like some antibodies for COVID viruses happen to be very similar to enzymes that have a task somewhere in the body. Because of the similarity it can in some ways do the job of that enzyme and this can be a problem. These antibodies are called abzymes. 

There is one abzyme that is similar to an enzyme that regulates blood pressure.

This is interesting because POTS – postural tachycardia syndrome – is a very common problem in people with post COVID and is all about regulating blood pressure: POTS is the inability to sustain a stable blood pressure, for instance when standing up.

“COVID-19 Antibody Discovery Could Explain Long COVID”

and

“ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients – PMC”

Virus protein

A protein from the COVID virus disrupts processes in the body, called nociception and angiogenesis. The former has to do with the processing of some kinds of pain, and the second with the function of growing new blood vessels (for example after a workout). This may be an explanation of some long COVID symptoms and also (rarely) long COVID-like symptoms following vaccination. 

“Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects? – PMC”

Micro-clotting

Researchers found that POTS from long COVID may be caused by micro-clotting in tiny blood vessels, and that in turn affects the uptake of oxygen in the cells. The micro-clotting may also cause an inflammatory response.

“Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID – PMC”

In this lovely article there is a very specific suggestion on how to get rid of the micro-clots: “A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications”

To summarise

There is a lot of research being done, they are finding out more and more about what is going on and all in all it seems quite possible to find a treatment. That’s very hopeful!

My next area of research is about the function of histamine in post COVID. I leave you with this great website about POTS and how to manage it: “Managing Symptoms of Postural Orthostatic Tachycardia Syndrome | Standing Up To POTS”

*All research for this article has been done in May 2024.

————————————

REFERENCES:

MUSCLE CELLS

Appelman B, Charlton BT, Goulding RP, Kerkhoff TJ, Breedveld EA, Noort W, Offringa C, Bloemers FW, van Weeghel M, Schomakers BV, Coelho P, Posthuma JJ, Aronica E, Joost Wiersinga W, van Vugt M, Wüst RCI. Muscle abnormalities worsen after post-exertional malaise in long COVID. Nat Commun. 2024 Jan 4;15(1):17. doi: 10.1038/s41467-023-44432-3. PMID: 38177128; PMCID: PMC10766651.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766651

CLEARANCE TIME

Antar AAR, Yu T, Demko ZO, Hu C, Tornheim JA, Blair PW, Thomas DL, Manabe YC. Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection. Front Immunol. 2023 Apr 28;14:1147549. doi: 10.3389/fimmu.2023.1147549. PMID: 37187756; PMCID: PMC10176965.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176965

METFORMIN

Bramante CT, Buse JB, Liebovitz D, Nicklas J, Puskarich MA, Cohen K, Belani H, Anderson B, Huling JD, Tignanelli C, Thompson J, Pullen M, Siegel L, Proper J, Odde DJ, Klatt N, Sherwood N, Lindberg S, Wirtz EL, Karger A, Beckman K, Erickson S, Fenno S, Hartman K, Rose M, Patel B, Griffiths G, Bhat N, Murray TA, Boulware DR. Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up. medRxiv [Preprint]. 2022 Dec 23:2022.12.21.22283753. doi: 10.1101/2022.12.21.22283753. PMID: 36597543; PMCID: PMC9810227.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810227

VACCINE 

Watanabe A, Iwagami M, Yasuhara J, Takagi H, Kuno T. Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine. 2023 Mar 10;41(11):1783-1790. doi: 10.1016/j.vaccine.2023.02.008. Epub 2023 Feb 8. PMID: 36774332; PMCID: PMC9905096.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9905096

LONG COVID PHENOTYPES

Zhang H, Zang C, Xu Z, Zhang Y, Xu J, Bian J, Morozyuk D, Khullar D, Zhang Y, Nordvig AS, Schenck EJ, Shenkman EA, Rothman RL, Block JP, Lyman K, Weiner MG, Carton TW, Wang F, Kaushal R. Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes. Nat Med. 2023 Jan;29(1):226-235. doi: 10.1038/s41591-022-02116-3. Epub 2022 Dec 1. PMID: 36456834; PMCID: PMC9873564.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873564

ABZYMES

Song Y, Myers R, Mehl F, Murphy L, Brooks B, Wilson JM, Kadl A, Woodfolk J, Zeichner SL. ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients. mBio. 2024 Apr 10;15(4):e0054124. doi: 10.1128/mbio.00541-24. Epub 2024 Mar 19. PMID: 38501835; PMCID: PMC11005375.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11005375

NEUROVASCULAR CROSSTALK

Talotta R. Impaired VEGF-A-Mediated Neurovascular Crosstalk Induced by SARS-CoV-2 Spike Protein: A Potential Hypothesis Explaining Long COVID-19 Symptoms and COVID-19 Vaccine Side Effects? Microorganisms. 2022 Dec 12;10(12):2452. doi: 10.3390/microorganisms10122452. PMID: 36557705; PMCID: PMC9784975.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784975

POTS AND MICROCLOTS

Kell DB, Khan MA, Kane B, Lip GYH, Pretorius E. Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID. J Pers Med. 2024 Jan 31;14(2):170. doi: 10.3390/jpm14020170. PMID: 38392604; PMCID: PMC10890060.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10890060

ANTI-CLOTTING RECIPE 

Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537-559. doi: 10.1042/BCJ20220016. PMID: 35195253; PMCID: PMC8883497.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883497

© 2024 Liv E. Helmfrid