Persistent Antiphospholipid Antibodies, Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome and Post-COVID Syndrome: 1 Year On

[SWAlexander]

Abstract
This is the first case report of a patient with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) with multiple persistent antiphospholipid antibody (aPL)-positivity more than a year after illness onset who also meets Global Consensus-2 criteria for mast cell activation syndrome (MCAS), suggesting pathological activation of the acquired and innate immune systems by SARS-CoV-2. While the patient continues to meet criteria for POTS 1 year on, her functional ability has improved significantly with therapy directed at MCAS, POTS and aPL-positivity.

LEARNING POINTS

• A subset of long-haul COVID-19 patients have postural orthostatic tachycardia syndrome (POTS), which can be diagnosed by a 10-minute in-office stand test.
• Antiphospholipid antibodies may be associated with POTS in patients with long-haul COVID-19 and have important clinical implications.
• Mast cell activation syndrome (MCAS) may be associated with long-haul COVID-19 (with or without POTS) and can often be easily treated, including with over-the-counter medications, supplements and dietary changes.

DISCUSSION
This patient’s history shows that post-COVID POTS may be very prolonged and possibly chronic. This is the first report describing the persistence of of multiple aPL more than one year after COVID-19 in a patient with clinical manifestations that have been published in association with aPL, that is, POTS. Autonomic neuropathy may be the initial manifestation of aPL-positivity [7]. Skin biopsy evaluating for suspected autonomic neuropathy was not performed because it would not change management. An abnormal skin biopsy is helpful for insurance approval when considering a trial of intravenous immunoglobulin, but as the present case illustrates, not all patients with autoimmunity and dysautonomia require immunoglobulin therapy.
APL-positivity in acute COVID-19 has been published by several groups [8, 9]. Infections are known to induce transient aPL production--a phenomenon which led to the requirement for persistent aPL positivity for ≥12 weeks before considering a diagnosis of antiphospholipid syndrome (APS) [10]. Only two studies have reported repeat aPL testing in acute COVID-19 patients. In one, 9 of 10 patients were aPL-negative 1 month later [8] and in another [9], three patients had persistent aPL-positivity, but only as late as 77 days after illness onset.
The persistent presence of aPL has important clinical implications, including an increased thrombotic risk as well as risk of pregnancy morbidity. While thrombosis and/or specific pregnancy morbidity are required for a ‘definite’ diagnosis of APS [10], the identification of aPL provides the opportunity to prevent thrombosis by avoiding exogenous oestrogen, controlling for vascular risk factors which act synergistically with aPL, and the use of thromboprophylaxis postoperatively or postpartum. In women of childbearing age, aPL identification provides the opportunity to reduce pregnancy morbidity.
This patient also met Global Consensus-2 criteria [11] for MCAS. Afrin et al. [4] recently published their hypothesis that excessive MCA in people with unrecognized and thus untreated MCAS may be at the root of severe acute as well as long-haul COVID-19. This patient fits their hypothesis. Medications which inhibit MCA have demonstrated efficacy and/or are being studied in COVID-19 [4].
The specific diagnoses of POTS, MCAS and aPL-positivity were critical to achieving clinical improvement in this case and suggest that patients with prolonged symptoms after COVID-19 should undergo stand testing to evaluate for POTS and serological testing for autoimmunity. Owing to the limitations of MCAS testing as well as the excellent safety profile of most agents used in the treatment of MCAS[11], consideration should be given to empiric treatment trials in long-haul COVID-19 patients with multisystem allergic and/or inflammatory symptoms suggesting MCAS. Patients with persistent aPL-positivity and migraine may respond dramatically to antithrombotic therapy [12]. Lastly, definite autoimmunity in a patient with severely disabling dysautonomia not improving with conservative therapies would support a trial of intravenous immunoglobulin which often results in dramatic improvement in this context [13].
Go to:
CONCLUSION
While SARS-CoV-2, like other autoimmune triggers, may incite a pathological innate and/or acquired immune response that may be prolonged, proper diagnoses and directed management may result in clinical improvement. Large studies of long-haul COVID-19 patients are imperative to better understand these complex multisystem disorders.
See complete publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046288/

 

[SWAlexander]

For everybody with vaccine injury.

This report was known since 06/23/21 and never reached the public.

Covid-19 and corona vaccination: keep an eye on the skin​

An infection with Sars-CoV2 or a corona vaccination - both can also have consequences for the skin. Prof. Tilo Biedermann, director of the clinic and polyclinic for dermatology and allergology at the Klinikum Rechts der Isar, explains what these are and how it comes about in an online lecture on Wednesday, June 23, at 6:15 p.m. In advance, he gives a little insight in the interview.

Why can skin symptoms occur in patients with a corona infection - and what can be concluded from this?​

Since the beginning of the corona pandemic, we have learned that Covid-19 causes some skin changes that we already know from other viral infectious diseases, such as hives or other rashes. Other skin changes, on the other hand, are relative or very specific to a corona infection: chilblain-like changes that mainly occur on the toes, hence also called "Covid toes". Rashes with blisters are also common, as is reddening of the skin that follows the course of blood vessels, which can progress to tissue death. We can learn things from this that are generally important with Covid-19: changes similar to chilblains occur primarily in children, adolescents and young adults, often with asymptomatic or mild courses. Corona PCR tests then often remain negative, although there have been cases of Covid-19 in the area that make infection seem likely. Skin rashes with blisters show, in turn, that Sars-CoV2 coronaviruses can directly attack the cells of the epidermis and mucous membrane. In such cases, one can always assume a Covid-19 disease. Redness that follows the course of vessels, with or without tissue death, indicates a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. that make an infection seem likely. Skin rashes with blisters show, in turn, that Sars-CoV2 coronaviruses can directly attack the cells of the epidermis and mucous membrane. In such cases, one can always assume a Covid-19 disease. Redness that follows the course of vessels, with or without tissue death, indicates a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. that make an infection seem likely. Skin rashes with blisters show, in turn, that Sars-CoV2 coronaviruses can directly attack the cells of the epidermis and mucous membrane. In such cases, one can always assume a Covid-19 disease. Redness that follows the course of vessels, with or without tissue death, indicates a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. that Sars-CoV2 coronaviruses can directly attack the cells of the epidermis and mucous membrane. In such cases, one can always assume a Covid-19 disease. Redness that follows the course of vessels, with or without tissue death, indicates a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. that Sars-CoV2 coronaviruses can directly attack the cells of the epidermis and mucous membrane. In such cases, one can always assume a Covid-19 disease. Redness that follows the course of vessels, with or without tissue death, indicates a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. there is a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients. there is a disorder in the cells that line the inside of the blood vessels. These cells, as well as blood platelets and coagulation factors, are then activated - changes that also occur in other organs with Covid-19: Such skin changes can provide an indication of this. They mainly occur in moderately to severely affected patients.

Skin reactions can also occur after a corona vaccination – which ones and what is the risk?​

The vast majority of people tolerate a corona vaccination without any problems: They feel a bit exhausted, sometimes a little sick or have a headache. A swollen arm can also appear with a little delay. Such reactions are also known from other vaccinations. A non-specific activation of the immune system by the vaccination can rarely worsen already existing skin diseases such as psoriasis or neurodermatitis for a short time or, extremely rarely, lead to their first appearance. All of these reactions are delayed and treatable. Reports of very rare immediate allergic reactions and allergic shock reactions (anaphylaxis) must be evaluated separately by allergists and vaccinators. Those affected often develop hives (urticaria) or sudden and extensive reddening of the skin (“flush”) shortly after the vaccination. It can also lead to shortness of breath and a sharp drop in blood pressure, very rarely to circulatory failure. Such a strong reaction occurs primarily with mRNA vaccines. The risk is probably two to three times higher than with other vaccines, but overall it is still very low. Unfortunately, some media reports have led to uncertainty, but this is largely unnecessary: not all allergy sufferers are at increased risk. For example, this risk is not increased in people who are only allergic to tree or grass pollen, bee or wasp venom. It can also lead to shortness of breath and a sharp drop in blood pressure, very rarely to circulatory failure. Such a strong reaction occurs primarily with mRNA vaccines. The risk is probably two to three times higher than with other vaccines, but overall it is still very low. Unfortunately, some media reports have led to uncertainty, but this is largely unnecessary: not all allergy sufferers are at increased risk. For example, this risk is not increased in people who are only allergic to tree or grass pollen, bee or wasp venom. It can also lead to shortness of breath and a sharp drop in blood pressure, very rarely to circulatory failure. Such a strong reaction occurs primarily with mRNA vaccines. The risk is probably two to three times higher than with other vaccines, but overall it is still very low. Unfortunately, some media reports have led to uncertainty, but this is largely unnecessary: not all allergy sufferers are at increased risk. For example, this risk is not increased in people who are only allergic to tree or grass pollen, bee or wasp venom. but overall still very low. Unfortunately, some media reports have led to uncertainty, but this is largely unnecessary: not all allergy sufferers are at increased risk. For example, this risk is not increased in people who are only allergic to tree or grass pollen, bee or wasp venom. but overall still very low. Unfortunately, some media reports have led to uncertainty, but this is largely unnecessary: not all allergy sufferers are at increased risk. For example, this risk is not increased in people who are only allergic to tree or grass pollen, bee or wasp venom.

What to do when people report a history of allergies before vaccination?​

For this purpose, an algorithm was developed in a short time, which is deposited with the Paul-Ehrlich-Institut (PEI) and shows how to act depending on the initial situation. This was possible because most of the reactions to mRNA vaccines are based on a specific immediate-type allergy to larger polyethylene glycol molecules (PEGs, synonym: macrogols). Such molecules are found in the lipid envelope of Moderna and Pfizer-BioNTech (“Comirnaty”) mRNA vaccines, but also in many everyday products. They are also ubiquitous in medicine, for example in laxatives, colon cleansing solutions, hydrogels or as excipients in tablets and in Moderna and Pfizer-BioNTech ("Comirnaty"). Exposure to it can lead to sensitization of the immune system in some people. In the process, type E antibodies (immunoglobulin E, IgE) are formed. The IgE are then bound by certain immune cells that have a high-affinity receptor for IgE: mast cells and basophilic granulocytes. If they come into contact with such PEGs again – in this case through the mRNA vaccination – they can bind to the cell-bound IgE. This bond activates the cells, which then immediately release messenger substances. These messenger substances in turn lead to the reactions of an immediate-type allergy. Therefore, prior to vaccination, appropriate clarification with skin or cellular tests (prick or intradermal test, basophil activation test) can be useful. Patients in whom we identified a PEG allergy before the vaccination had already had an allergic reaction to PEGs in the past, for example when preparing for a colonoscopy. In such cases, an alternative vaccine can be used. For all others, the observation period is extended directly after the vaccination - in accordance with theAlgorithm of the PEI . Media warnings are therefore entirely justified for patients with a PEG allergy. However, these reports affect very few people.

https://www-mri-tum-de.translate.go..._sl=de&_x_tr_tl=en&_x_tr_hl=en&_x_tr_pto=wapp

 

[ChookityPop]

Abstract
This is the first case report of a patient with post-COVID-19 postural orthostatic tachycardia syndrome (POTS) with multiple persistent antiphospholipid antibody (aPL)-positivity more than a year after illness onset who also meets Global Consensus-2 criteria for mast cell activation syndrome (MCAS), suggesting pathological activation of the acquired and innate immune systems by SARS-CoV-2. While the patient continues to meet criteria for POTS 1 year on, her functional ability has improved significantly with therapy directed at MCAS, POTS and aPL-positivity.

LEARNING POINTS

• A subset of long-haul COVID-19 patients have postural orthostatic tachycardia syndrome (POTS), which can be diagnosed by a 10-minute in-office stand test.
• Antiphospholipid antibodies may be associated with POTS in patients with long-haul COVID-19 and have important clinical implications.
• Mast cell activation syndrome (MCAS) may be associated with long-haul COVID-19 (with or without POTS) and can often be easily treated, including with over-the-counter medications, supplements and dietary changes.

DISCUSSION
This patient’s history shows that post-COVID POTS may be very prolonged and possibly chronic. This is the first report describing the persistence of of multiple aPL more than one year after COVID-19 in a patient with clinical manifestations that have been published in association with aPL, that is, POTS. Autonomic neuropathy may be the initial manifestation of aPL-positivity [7]. Skin biopsy evaluating for suspected autonomic neuropathy was not performed because it would not change management. An abnormal skin biopsy is helpful for insurance approval when considering a trial of intravenous immunoglobulin, but as the present case illustrates, not all patients with autoimmunity and dysautonomia require immunoglobulin therapy.
APL-positivity in acute COVID-19 has been published by several groups [8, 9]. Infections are known to induce transient aPL production--a phenomenon which led to the requirement for persistent aPL positivity for ≥12 weeks before considering a diagnosis of antiphospholipid syndrome (APS) [10]. Only two studies have reported repeat aPL testing in acute COVID-19 patients. In one, 9 of 10 patients were aPL-negative 1 month later [8] and in another [9], three patients had persistent aPL-positivity, but only as late as 77 days after illness onset.
The persistent presence of aPL has important clinical implications, including an increased thrombotic risk as well as risk of pregnancy morbidity. While thrombosis and/or specific pregnancy morbidity are required for a ‘definite’ diagnosis of APS [10], the identification of aPL provides the opportunity to prevent thrombosis by avoiding exogenous oestrogen, controlling for vascular risk factors which act synergistically with aPL, and the use of thromboprophylaxis postoperatively or postpartum. In women of childbearing age, aPL identification provides the opportunity to reduce pregnancy morbidity.
This patient also met Global Consensus-2 criteria [11] for MCAS. Afrin et al. [4] recently published their hypothesis that excessive MCA in people with unrecognized and thus untreated MCAS may be at the root of severe acute as well as long-haul COVID-19. This patient fits their hypothesis. Medications which inhibit MCA have demonstrated efficacy and/or are being studied in COVID-19 [4].
The specific diagnoses of POTS, MCAS and aPL-positivity were critical to achieving clinical improvement in this case and suggest that patients with prolonged symptoms after COVID-19 should undergo stand testing to evaluate for POTS and serological testing for autoimmunity. Owing to the limitations of MCAS testing as well as the excellent safety profile of most agents used in the treatment of MCAS[11], consideration should be given to empiric treatment trials in long-haul COVID-19 patients with multisystem allergic and/or inflammatory symptoms suggesting MCAS. Patients with persistent aPL-positivity and migraine may respond dramatically to antithrombotic therapy [12]. Lastly, definite autoimmunity in a patient with severely disabling dysautonomia not improving with conservative therapies would support a trial of intravenous immunoglobulin which often results in dramatic improvement in this context [13].
Go to:
CONCLUSION
While SARS-CoV-2, like other autoimmune triggers, may incite a pathological innate and/or acquired immune response that may be prolonged, proper diagnoses and directed management may result in clinical improvement. Large studies of long-haul COVID-19 patients are imperative to better understand these complex multisystem disorders.
See complete publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046288/

This is basically me just from another infection trigger.. EBV and/or Enterovirus (echovirus 9). Or lyme... Or something else?

 

[SWAlexander]

I believe the allergy comes, at least in my case, from polyethylene glycol (PEG) one can find in many meds such as Gelatin capsules, etc.
Polyethylene glycol (PEG), also known as macrogol or E1521, is a commonly used bulking and stabilizing agent.

Abstract​

Polyethylene glycol (PEG), also known as macrogol, is an excipient in numerous medications, health care products, cosmetics, and foods. It acts as an inert bulking, or stabilizing, agent. Despite its ubiquity, including in 2 of the newly launched vaccines against SARS‐CoV‐2, awareness of PEG allergy remains low. We present 6 cases of acute hypersensitivity to PEG. Accurate diagnoses in these cases posed a challenge, and although the triggering agents differed, PEG was demonstrated as the common culprit. All cases were female, with a mean age of 36.4 years. Four patients were originally suspected to have nonsteroid anti‐inflammatory drug allergy, and 2 had a history of chronic spontaneous urticaria and angioedema. Biphasic allergic reactions featured prominently in this case series. Diagnosis relies on a high index of suspicion leading to a focused clinical history, supported by skin tests with PEG solutions to demonstrate sensitization. This case series highlights important clinical features of this rare, potentially serious, and increasingly recognized excipient allergy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014770/

 

[ChookityPop]

I believe the allergy comes, at least in my case, from polyethylene glycol (PEG) one can find in many meds such as Gelatin capsules, etc.
Polyethylene glycol (PEG), also known as macrogol or E1521, is a commonly used bulking and stabilizing agent.

Abstract​

Polyethylene glycol (PEG), also known as macrogol, is an excipient in numerous medications, health care products, cosmetics, and foods. It acts as an inert bulking, or stabilizing, agent. Despite its ubiquity, including in 2 of the newly launched vaccines against SARS‐CoV‐2, awareness of PEG allergy remains low. We present 6 cases of acute hypersensitivity to PEG. Accurate diagnoses in these cases posed a challenge, and although the triggering agents differed, PEG was demonstrated as the common culprit. All cases were female, with a mean age of 36.4 years. Four patients were originally suspected to have nonsteroid anti‐inflammatory drug allergy, and 2 had a history of chronic spontaneous urticaria and angioedema. Biphasic allergic reactions featured prominently in this case series. Diagnosis relies on a high index of suspicion leading to a focused clinical history, supported by skin tests with PEG solutions to demonstrate sensitization. This case series highlights important clinical features of this rare, potentially serious, and increasingly recognized excipient allergy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014770/

1 year before the onset of my disease I had 2 episodes of anaphylaxis from eating banana which I had eaten weekly basically all my life but suddenly couldnt anymore.
Ive eaten carnivore since 2019 after my relapse. I should step up my MCAS treatment and see if it helps.

 

[SWAlexander]

MCAS treatment

What would you take to stop MCAS?
Can you eat anything with gelatin? I don´t.
I also can no longer eat bananas.

 

[SWAlexander]

Update on Polyethylene glycol (PEG) a product in every vaccine.

Shocking to learn about the damage done by Polyethylene glycol (PEG)
Yes, PEG can damage phospholipids. PEG, or polyethylene glycol, is a long-chain polymer that is often used as a solvent or carrier in pharmaceutical applications. It can also be used as a coating on nanoparticles or other materials.

PEG can damage phospholipids by disrupting their structure. Phospholipids are made up of two fatty acid chains and a glycerol backbone. The fatty acid chains are hydrophobic, meaning they repel water. The glycerol backbone is hydrophilic, meaning it attracts water. This allows phospholipids to form a bilayer in water, with the hydrophobic fatty acid chains facing away from the water and the hydrophilic glycerol backbone facing towards the water.

PEG is also hydrophobic. When PEG is added to a solution of phospholipids, it can disrupt the bilayer structure by interacting with the hydrophobic fatty acid chains. This can lead to the formation of aggregates, or clumps, of phospholipids. The aggregates can be too large to pass through cell membranes, which can prevent cells from taking up nutrients or expelling waste products.

In addition to disrupting the bilayer structure, PEG can also damage phospholipids by oxidizing them. Oxidation is a chemical reaction that can damage cell membranes and other biomolecules. PEG can promote oxidation of phospholipids by acting as a free radical scavenger. Free radicals are unstable molecules that can damage cells. When PEG scavenges free radicals, it can create new free radicals that can damage phospholipids.

The damage caused by PEG to phospholipids can vary depending on the concentration of PEG, the type of phospholipids, and the cell type. In general, higher concentrations of PEG and longer PEG chains are more likely to damage phospholipids. Some types of phospholipids, such as phosphatidylcholine, are more susceptible to damage by PEG than others. And certain cell types, such as red blood cells, are more sensitive to PEG damage than others.

The damage caused by PEG to phospholipids can have a number of negative effects on cells. It can disrupt cell membrane function, leading to decreased nutrient uptake and increased waste product accumulation. It can also damage cell signaling pathways, leading to impaired cell growth and differentiation. In some cases, PEG damage to phospholipids can be fatal to cells.

For these reasons, it is important to be aware of the potential for PEG to damage phospholipids when using it in pharmaceutical applications. PEG should be used at the lowest possible concentration that is effective, and it should be used in conjunction with other measures to protect cells from damage.