Autoimmune and inflammatory thyroid diseases following vaccination with SARS-CoV-2 vaccines: from etiopathogenesis to clinical management

Abstract

Since the Covid-19 pandemic emerged in 2019, several adenoviral-vectored, mRNA-based and inactivated whole-virus vaccines have been developed. A massive vaccination campaign has been undertaken around the world, and an increasing number of SARS-CoV-2 vaccine-induced thyroid diseases have been described in the literature. Subacute thyroiditis has been reported in 52 patients, mean age 45.5 ± 1.8 years, mainly in women ( n = 39). Graves’ disease is more frequent in women ( n = 22) than in men ( n = 10), mean age 46.2 ± 2.6 years, reported as new onset, recurrent or exacerbation of well-controlled hyperthyroidism. The mean time to symptoms onset is 9.0 ± 0.8 days in subacute thyroiditis, and 15.1 ± 2.6 days in Graves’ patients. Rare patients ( n = 6) present silent or painless autoimmune thyroiditis. Thyroid function and autoimmune tests, inflammatory markers, thyroid echography with colour flow Doppler, radio-activity uptake on thyroid scan, medical treatment and follow-up are described and compared in patients with SARS-CoV-2 vaccine-induced thyroid diseases. The underlying pathogenic mechanisms of vaccine-induced thyroid diseases, molecular mimicry (various SARS-CoV-2 proteins sharing a genetic homology with a large heptapeptide human protein) or autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are discussed in the context of predisposition or genetic susceptibility. The benefits of SARS-CoV-2 vaccination far outweigh the potential vaccine-induced adverse effects, but clinicians should be aware of possible autoimmune and inflammatory thyroid diseases, and can advise patients to seek medical assistance when experiencing anterior neck pain, fever or palpitations following SARS-CoV-2 vaccines. Further studies are warranted to investigate the etiopathogenesis and to clarify the factors which predispose patients to SARS-CoV-2 vaccine-induced thyroid diseases.

Graves’ orbitopathy post-SARS-CoV-2 vaccines: report on six patients

“…In all reported patients with GO following COVID-19 vaccination, no triggering events (increased TSH concentrations, changes in smoking status, pregnancy, recent surgeries, radioiodine treatment) were observed in their medical history other than COVID-19 vaccination and the timing between the new-onset or reactivation of GO and SARS-CoV-2 vaccines was similar to that stated in previous reports of autoimmune and inflammatory diseases following COVID-19 vaccination [ 2 ]. Considering the high vaccination coverage, it is possible that the relationship between the occurrence of GO and COVID-19 vaccination was coincidental.…”

“…Adjuvants enhance the immunogenicity of vaccines, increase both innate and adaptive immune response and can induce the formation of autoantibodies. Autoimmune thyroid diseases have been reported to be related to ASIA syndrome after human papillomavirus, influenza, hepatitis B vaccination [ 21 – 26 ] and most recently after COVID-19 vaccines [ 2 , 5 , 27 – 29 ]. In the BNT162b2 mRNA vaccine, polyethylene glycol (PEG) conjugates stabilise the lipid nanoparticles and may act as adjuvants to trigger an autoimmune reaction following SARS-CoV-2 vaccination.…”

“…An increasing number of autoimmune and inflammatory-related side effects are being reported following COVID-19 vaccination (thrombotic thrombocytopenia, Guillain–Barré syndrome, myocarditis/pericarditis, type 1 diabetes mellitus, premature ovarian failure, adrenal insufficiency). Moreover, autoimmune and inflammatory-related thyroid disorders such as Graves’ disease, subacute thyroiditis and silent (painless) thyroiditis have been described following SARS-CoV-2 vaccines [ 2 – 5 ] but autoimmune and inflammatory orbital adverse complications are uncommon post-COVID-19 vaccination [ 6 ].…”

Endocrine system after 2 years of COVID-19 vaccines: A narrative review of the literature

“…Furthermore, specific HLA haplotypes, such as HLA-B35, may have a role in the susceptibility to SAT in general population ( 124 ); interestingly, the association between vaccine-related SAT development and HLA-B35 was found in a recent study ( 26 ) even if further data are needed to confirm this relationship.…”

Post-COVID Endocrine Disorders: Putative Role of Molecular Mimicry and Some Pathomorphological Correlates

“…SP of various Coronaviruses shared greatest number of epitopes with endocrine autoantigens, compared to their MP or NP. Thyroid autoantigens were most active in "sharing" their epitopes with highly pathogenic Coronaviruses, which corresponds to growing number of cases of autoimmune thyroid diseases cases described during and after COVID-19 [40] and even few of themafter anti-COVID-19 vaccination [41]. At the same time seasonal Coronaviruses quite often shared their immunodominant pentapeptides with several autoantigens of pancreatic islet β-cells.…”