Autoimmunity is the condition where the body’s immune system attacks itself. The immune system loses its controlled and measured response to germs and becomes uncontrolled.
Many factors cause autoimmunity, and viruses are one of them.
A few of these viruses are the Human T- cell leukemia virus, type 1, Herpes virus-6, Hepatitis A and C virus, and the German measles virus.
These viruses have been implicated in the formation of autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and autoimmune hepatitis.
SARS-CoV-2
The present COVID-19 pandemic is due to the SARS-CoV-2 virus. It causes mild to moderate COVID-19 in the majority.
Unfortunately, for some patients, especially the old and those with comorbidities like hypertension and diabetes, the clinical course can be severe and deadly.
In severe COVID-19 patients develop Acute Respiratory Distress Syndrome or ARDS. The lungs get filled with fluid and become stiff in ARDS.
A closer of severe COVID-19 cases shows a similarity with autoimmune diseases in their clinical course, blood work, x-ray findings, and autopsy findings.
Autoimmune conditions in patients with COVID-19
The following are autoimmune diseases that happened after the patients were diagnosed with COVID-19. A detailed description of these diseases is beyond this article’s scope but can be seen in reference [1].
Immune Thrombocytopenic Purpura
Immune Thrombocytopenic Purpura (ITP) happens when antibodies bind to the platelets. The result is a lower platelet count. If the platelets become critically low, it can lead to bleeding and can be life-threatening.
ITP has been reported in a grown woman and a child with COVID-19.
Guillian-Barré Syndrome
Guillian-Barré syndrome (GBS) is a form of demyelinating disease. It happens when the immune system attacks the outer lining of the nerves making the nerves ineffective.
GBS presents a progressive weakness starting from the legs. The paralysis slowly goes up the body in days or weeks.
There have been 4 cases of GBS in COVID-19 reported in Italy, one in Iran, and another from China.
Miller Fischer syndrome
Miller Fischer syndrome is a mild form of GBS. It presents as weak joint reflexes, ataxia or abnormal walking, and paralysis of the muscles that make the eyeballs move leading to double vision.
Two patients from Spain have been reported to have MFS and COVID-19.
Antiphospholipid antibodies and thrombosis
Antiphospholipid antibodies lead to abnormal blood clot formation. These blood clots can be found deep in the legs’ veins, causing Deep Venous Thrombosis or DVT.
Blood clots can break off from the DVT and end up in the lungs to cause Pulmonary Embolism, a life-threatening condition.
Strokes with COVID-19 can also happen, and it is usually seen in the elderly. However, it can also happen in the younger age group. Five cases with ages 33-49 have been reported.
Antiphospholipid bodies are common in all serious COVID-19 cases. That is why a blood thinner like heparin and enoxaparin are part of the treatment of severe COVID-19 like the MATH+ regimen.
Kawasaki-like disease – KD
Kawasaki disease is an inflammation of the blood vessels or vasculitis in the whole body. KD is usually seen in children less than 5 years old.
Kawasaki Shock Syndrome or KSS is seen in 5% of children with KD. KSS is associated with hypotension or low blood pressure. The hypotension is due to the “leaking” blood vessels. The authors of the paper in [1] are aware of ten cases of KSS in Italy.
In all of the diseases mentioned above, the treatment included intravenous immune globulin to bind the antibodies and steroids to suppress the hyperimmune system.
Preexisting Autoimmune Rheumatic Diseases and COVID-19
Early in the pandemic, it was expected that people with autoimmune diseases would fare badly. That’s because they are taking medications that lower their immune response to infections.
However, patients with Systemic Lupus Erythematosis or SLE, Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease did well.
It turned out, the medications they are taking, like Tocilizumab and Sarilumab, both anti-interleukin-6 inhibitors, anakinra, which is an interleukin-1 inhibitor, and Disease-Modifying anti-rheumatic drugs or DMARDs like methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine are medicines that control autoimmune diseases.
In short, people with autoimmune diseases are already taking drugs that prepared them for the SARS-CoV-2 virus that can cause autoimmune disease.
This adds proof that severe COVID-19 is more of an autoimmune disease brought about by an infectious agent—the SARS-CoV-2.
This is another explanation of why the MATH+ regimen used in severe COVID-19 patients decreases mortality. The M is for methylprednisolone, a steroid drug that modulates a rampaging immune response.
This begs the question; How do viruses like the SARS-CoV-2 virus cause autoimmunity?
Molecular mimicry
Molecular mimicry is the similarity between the proteins and peptides of the human body and viruses.
Proteins and peptides are made up of amino acids that are chained together. Peptides are short chains of amino acids.
One way to name the peptides is to put a Greek prefix in front based on the number of amino acids. Thus, if there are five in a chain, it is called a pentapeptide. If there are seven in a chain, it is a heptapeptide, and so on.
The minimum number of amino acids in a peptide chain that can elicit an antibody response is five.
The table below shows the heptapeptides that are common between the SARS-CoV-2 spike glycoprotein and the human body.
The clinical implication of molecular mimicry is the immune response that will be raised against a viral peptide can also cross-react with a human protein leading to an autoimmune disease.
As an example, in the table above, the antibody and other immune responses formed against the SARS-CoV-2 peptide SSTASAL can also attack the human protein 40S ribosomal S13.
40S ribosomal S13 is a part of the ribosome that is responsible for protein synthesis.
This is what the authors of Covid-19 and autoimmunity said about the table above.
The clinical scenario that emerges is upsetting. Inded, the list of proteins reported in the table – when altered – configurate almost all the diseases that have been described in association with SARS-CoV-2.
Two examples from the table are 1) Histone-lysine N-methyltransferase 2C that may associate with neurodevelopmental
disorders., seizures, behavioral abnormalities, and2) Interleukin-7 that plays a central, critical role in the regulation of the immune system and associates with severe lymphopenia when deficient.
But there is more.
A letter to an editor from the Journal Clinical Immunology [2] included a table that shows the molecular mimicry between the pentapeptides of SARS-CoV-2 spike glycoprotein and the human surfactant-related proteins.
That table is presented below.
Note the 25 pentapeptides that are similar between the SARS-CoV-2 and human surfactant proteins.
Lung surfactants decrease the surface tension in the lungs and enable us to breathe easier. Lack of surfactants can lead to Acute Respiratory Distress Syndrome.
Take note that the common pentapeptides between human surfactant and HCoV-229E, one of the common coronaviruses that cause mild lower respiratory tract symptoms, are less than the SARS CoV-2.
COVID-19 Vaccine and Molecular Mimicry
Due to the risk of developing autoimmune diseases from molecular mimicry, the authors in both articles [1] and [2] warn against using vaccines based on the entire SARS-CoV-2 spike glycoproteins. The two articles were published in May and March 2020, respectively.
Since then, Pfizer has obtained Emergency Use Authorization for its modified RNA vaccine. What does it have?
This is from the product insert of the PFIZER-BIONTECH COVID-19 VACCINE.
Each dose of the Pfizer-BioNTech COVID-19 Vaccine contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2.
I think they mean the whole spike protein is in the vaccine.
As of now, thousands have been vaccinated with the Pfizer vaccine. Hopefully, the vaccine will be effective in preventing serious COVID-19 and not produce more autoimmune diseases.
Knowledge about Covid-19 is rapidly evolving. Information may update as new researches are done. Stay current by subscribing. Feel free to share.
Don’t Get Sick!
References:
- Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. doi:10.1016/j.autrev.2020.102597
- Kanduc D, Shoenfeld Y. On the molecular determinants of the SARS-CoV-2 attack. Clin Immunol. 2020;215:108426. doi:10.1016/j.clim.2020.108426
- Oldstone MB. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819-20. doi: 10.1016/0092-8674(87)90507-1. Erratum in: Cell 1987 Dec 4;51(5):878. PMID: 3621346.
- Caso F, Costa L, Ruscitti P, et al. Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects?. Autoimmun Rev. 2020;19(5):102524. doi:10.1016/j.autrev.2020.102524
- Vogel et al. A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates.
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