The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused severe or critical illness in a significant minority of patients. In addition to the more than 3.7 million deaths worldwide, the virus has forced the shut-down of entire economies, and closure of international borders between countries, to contain its spread.

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COVID-19 vaccine safety in autoimmune patients

Vaccines have provided a way out, seemingly, but many are hesitant to take the shot because of the rapidity with which these were developed and approved. Another population that may have significant levels of hesitancy or unwillingness is patients with autoimmune rheumatic or neuroinflammatory conditions, such as lupus (systemic lupus erythematosus), rheumatoid arthritis (RA), or multiple sclerosis (MS).

Most such patients are on immunosuppressive agents, ranging from three out of four patients with RA or MS to 98% of those with lupus or other vasculitic condition. Over 40% were on biologics, mostly tumor necrosis factor (TNF) inhibitors in the form of monoclonal anti-TNF antibodies, or anti-CD20 antibodies.

Such patients may fear either that the vaccine may trigger severe adverse reactions, or that the autoimmune condition may be worsened. On the other hand, these patients could be at a higher risk of severe COVID-19.

In the absence of a vaccine and a scarcity of proven therapeutic options, nonpharmacological measures such as shielding, case isolation, strict hand hygiene, and social distancing are key measures to protect this vulnerable group of patients.”

A recent study showed that medical advice was adequate to reassure these patients as to the safety of vaccination with their condition, boosting the overall willingness from approximately 60% to over 80%.

Similarities between autoimmune disease and COVID-19

Autoimmune diseases are those defined by the presence of autoantibodies that trigger chronic inflammation with immune-mediated damage to the tissues. It is caused by the loss of immune tolerance, the result of dysregulated immunity. This eerie picture resembles the sequence of events in severe or critical COVID-19 as well.

In this condition, the immune response is both protective and potentially dangerous. While the neutralizing antibodies and T cell immunity help to clear the virus by killing infected cells, the excessive release of pro-inflammatory cytokines and chemokines, stimulated by damage-associated molecular patterns (DAMPs), may cause severe multi-organ damage.

Neutrophilia and extrafollicular B cell activation is also observed, especially in critical COVID-19, along with macrophage activation syndrome in response to the well-known cytokine storm. Activated macrophages differentiate into inflammatory macrophages with the M1 phenotype, secreting inflammatory mediators. Mast cells may also contribute, following their activation by SARS-CoV-2. Meanwhile, neutrophil activation and the formation of neutrophil extracellular traps (NETosis) play their role.

These phenomena are also seen in antiphospholipid syndrome and other autoimmune disorders.

Again, corticosteroids and anti-inflammatory biologics such as tocilizumab, which are used in autoimmune disease, have been found to be useful in COVID-19.  

Molecular mimicry in COVID-19 and autoimmune disease

Molecular mimicry is one of the fundamental mechanisms of autoimmune disease. One stimulus for antigenic molecular mimicry is the exposure of the immune system to viral antigens bearing epitopes, or antibody binding sites, that are almost identical to human protein sequences. The antibodies elicited by these antigens are thus cross-reactive to viral and human epitopes.

A classic example of such molecular mimicry in autoimmune disease is the cross-reactivity between antibodies formed in response to the Epstein–Barr virus (EBV) Nuclear Antigen-1 (EBNA-1) and human Sm and Ro autoantigens, resulting in lupus. EBNA-1 has also been linked to multiple sclerosis via reactivity with myelin basic protein, and structural similarity to beta-synuclein.

SARS-CoV-2 infection may promote molecular mimicry via human molecular chaperones, mostly heat shock proteins, causing autoimmune polyneuropathic syndromes like Guillain-Barré syndrome, among others. This possibility must be explored for its ability to explain the protean manifestations of COVID-19.

Autoantibodies in COVID-19

In fact, several studies have shown that commonly assayed autoantibodies such as antinuclear antibodies (ANA), anticytoplasmic neutrophil antibodies (ANCA) and antiantiphospholipid (APL) antibodies are positive in a third to a half of all COVID-19 patients and that their presence was a marker of more severe disease. APL and lupus anticoagulant especially was linked to thrombotic complications and a hyperinflammatory state, respectively.

Autoimmune disease following COVID-19

Several researchers have noted the occurrence of autoimmune disease after COVID-19, including Guillain-Barré syndrome, cold agglutinin syndrome (CAS) and autoimmune hemolytic anemia, and one case of lupus.

Risks faced by autoimmune patients during COVID-19

The actual comorbidities that were found more frequently in this group of COVID-19 patients who have pre-existing autoimmune disease include hypertension, chronic kidney disease, heart disease, chronic obstructive lung disease, and the use of blood thinners. They showed a high prevalence of psoriasis, RA, and vasculitis.

The occurrence of COVID-19 in these patients was associated with higher rates of respiratory complications, such as pneumonia, which was diagnosed in up to 53% of them, acute respiratory distress syndrome (ARDS) in up to 43%, and death within 30 days in approximately one in four patients.

All these adverse outcomes were increased in the group of autoimmune disease patients with COVID-19 compared to patients with autoimmune disease who developed influenza, with up to 36% having pneumonia, up to 29% ARDS, and death within 30 days in 4%.

Interestingly, though COVID-19 is known to be more severe in men, most of the patients with autoimmune disease who required hospitalization for COVID-19 were women. They were also older and had other underlying diseases such as hypertension, chronic kidney disease, and heart disease.

Overall, therefore, COVID-19 carries a greater risk to this group of patients. Researcher Eng Hooi Tan says, “We found particular comorbidities that occurred more frequently in patients with autoimmune conditions hospitalized with COVID-19 vs. those diagnosed with COVID-19.” Further work is required to identify predictors of adverse outcomes in this group of patients.  

Moreover, autoimmune patients may have stopped taking immunosuppressive medications, either out of fear of infection or because they were not available; or could not follow up with their healthcare providers. Since this is linked to disease flares, remote medical care should be provided consistently for these patients.

Finally, while the risk of COVID-19 among this group is not clear, some studies, at least, have shown that it is important that they conform to mitigation measures to avoid viral transmission while continuing to adhere to their therapeutic regimens. Healthcare providers should also encourage these patients to be vaccinated against the virus, as well.

References:

• Liu, Y. et al. (2021). COVID-19 and autoimmune diseases. Current Opinions in Rheumatology. https://dx.doi.org/10.1097%2FBOR.0000000000000776. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880581/
• Boekel, L. et al. (2021). Perspective of patients with autoimmune diseases on COVID-19 vaccination. The Lancet. https://doi.org/10.1016/S2665-9913(21)00037-0. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00037-0/fulltext
• Laday, J. et al. (2021). COVID-19 more severe than influenza in patients with autoimmune disease. https://www.healio.com/news/rheumatology/20210329/covid19-more-severe-than-influenza-in-patients-with-autoimmune-disease

Further Reading

• All Coronavirus Disease COVID-19 Content
• The COVID-19 Pandemic: What have the experts learned?
• What Mutations of SARS-CoV-2 are Causing Concern?
• Protecting Your Mental Health During a Pandemic
• How has the COVID-19 Pandemic Impacted Global Health?

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.