COVID-19 and Autoimmunity

A growing body of evidence accumulated in recent years suggests a strong correlation between SARS-CoV-2 infection and autoimmunity. So far researchers looking at our immune response to COVID-19 have discovered both exaggerated and misdirected immune responses.

The exaggerated response would include the cytokine storms witnessed with many acute hospitalised cases, but the misdirected immune response refers to a kind of ‘friendly fire’, either a re-activation of existing autoantibodies or the production of new antibodies that sadly direct their attack on tissue that is neither foreign nor pathological, i.e. self-tissue, hence the description: misdirected ‘autoantibodies’.

So far the clinical spectrum of autoimmune-related manifestations in COVID-19 patients ranges from organ specific autoimmune conditions to the more systemic, inflammatory conditions like vasculitis, rheumatic arthritic type conditions, and multisystem inflammatory syndrome.

In the UK, over 4 million people already have an autoimmune condition, there are over 70 such conditions to choose from and some patients suffer more than one. Regardless of the tissue or organ affected, the person’s immune system has got its wires crossed by attacking healthy tissue instead of infectious agents. Although it’s known some conditions are triggered by an initiating virus that invaded the tissue in question, or the virus has peptides similar enough in structure to some human tissue cells, to trick the immune system (through molecular mimicry) into attacking ‘self’.

The immune questions now posed by researchers include:

1) Does established autoimmunity predispose to severe COVID-19?

2) Can SARS-CoV-2 infection trigger de novo autoimmunity?

3) Do autoantibodies contribute to, or exacerbate Long-COVID?

4) Can the COVID vaccine induce autoimmunity in the susceptible?

So far studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonise cytokine signalling, and 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons. There are numerous case reports of patients developing classifiable autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis, and type 1 diabetes, concomitantly with or immediately following SARS-CoV-2 infection.

Researchers are also examining COVID-19 as a potential risk for new-onset autoimmune diseases, such as antiphospholipid syndrome, Guillain-Barré syndrome, Kawasaki disease and numerous others. It is also suggested that the common early symptom involving loss of smell – anosmia – may be another autoimmunity manifestation.

Data so far strongly suggests that some severe COVID-19 cases can be explained by preexisting autoantibodies. With regard to ‘de novo’ autoantibody formation, a variety of such antibodies have been detected in patients hospitalized with severe COVID-19, however, it needs to be confirmed if these antibodies are contributors to severe disease or simply a by-product, secondary to marked inflammation.

In terms of Long-COVID, it’s only a matter of time before firm links are shown between the reactivation or exacerbation of certain autoantibodies and the chronic fatigue, with brain fog symptoms associated with Long-COVID.  One study of Covid patients has confirmed that the presence of autoantibodies was linked to longer-lasting symptoms. Going into the study, 6% of the patients had autoimmune conditions, but 44% of Covid patients who still had symptoms after two to three months had autoantibodies in their blood.

In conclusion, like Chronic Fatigue, Long-COVID is most likely multifactorial.  In some it may be a new, post-infective autoimmune condition,  in others it may be the result of an exacerbation of a secondary autoimmune disease like lupus or rheumatoid arthritis, for which some patients have yet to be diagnosed.

Going forward, the COVID-19 pandemic and the research funding it attracts may just provide an excellent opportunity to more precisely determine how a viral infection can trigger, and exacerbate autoimmunity.

The final question . . .

But my final question would be, as it is now established that molecular mimicry exists between SARS-CoV-2 and human components, if autoimmune manifestations start appearing in vaccinated individuals who have not had exposure to the wild-type virus, should mRNA sequences coding for peptides shared with humans, be removed from vaccines?

Research

Gracia-Ramos A et al., (2021) New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells v10(12)

Churilov L et al., (2021) Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID-19 Endocrine Autoimmunity? Pathophysiology 25;29(3):486-494

Maedeh V et al.,(2022)  Molecular mimicry, hyperactive immune system, and SARS-COV-2 are three prerequisites of the autoimmune disease triangle following COVID-19 infection. Review: Int. Immunopharmcol.

Knight JS et al., (2021) The Intersection of Covid-19 & Autoimmunity. JCI 131(24)

Kiho Son et al., (2022) Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long-COVID symptoms. Euro Respiratory Journal