key: cord-0961732-x7yf33zu
authors: Ratnayake, Gowri M.; Dworakowska, Dorota; Grossman, Ashley B.
title: Can COVID‐19 immunisation cause subacute thyroiditis?
date: 2021-07-17
journal: Clin Endocrinol (Oxf)
DOI: 10.1111/cen.14555
sha: 818ade40c8caf27f09a47d8785e8cf83506114c2
doc_id: 961732
cord_uid: x7yf33zu

nan

To the Editor, Subacute thyroiditis is often triggered by viral infections. In the current global pandemic of COVID-19 infection, there are several case reports of COVID-19-related subacute thyroiditis. 1, 2 Moreover, the rate of vaccination against COVID-19 had risen worldwide with over 1 billion people being vaccinated with some form of the vaccine to date. 3 We now report a case of subacute thyroiditis probably related to immunisation with the COVID-19 AstraZeneca vaccine.

A 75-year-old male presented with pain and tenderness around the front of his neck some 14 days following immunisation against COVID-19 with the AstraZeneca vaccine (ChAdOx1, Vaxzevria). Our patient had symptoms and some signs of thyrotoxicosis, confirmed biochemically, with no family history and negative thyroid antibodies, including the TSH-receptor antibodies. This, together with his negative pertechnetate scan, renders the diagnosis of subacute thyroiditis highly probable. His neck pain has now settled. We feel that his case should be reported at this juncture due to the temporal association with his COVID-19 immunisation.

It is now well established that subacute thyroiditis may be associated with COVID-19 infection, albeit rarely. 1,2 To date, there is a reported case of subacute thyroiditis following the Pfizer-BioNTech messenger RNA vaccine for COVID-19 4 and three cases of subacute thyroiditis following CoronaVac® which contains inactivated SARS-CoV-2 virus. 3 There are further two cases of new-onset of Graves' disease following COVID-19

Pfizer-BioNTech immunisation, possibly due to an autoimmune inflammatory syndrome induced by adjuvants (ASIA). 5 Adjuvants are an essential part of the vaccine, and postvaccination phenomena have been described with autoimmune endocrine diseases (mostly after HPV, influenza and hepatitis B vaccine). 6 The clinical spectrum regarding thyroid disease includes both Hashimoto's thyroiditis and Graves' disease, but reports include ovarian failure and type 1 diabetes. 7 Although ASIA might explain the mechanism of thyroiditis by adjuvants, the AstraZeneca vaccine contains recombinant replicationdeficient chimpanzee adenovirus vector encoding the SARS CoV-2 spike glycoprotein, produced in the genetically modified human embryonic kidney 293 cells, 8, 9 and other mechanisms may be involved in immunisation-induced thyroiditis. SARS CoV-2 spike protein enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor, and there is evidence to suggest that thyroid cells express the ACE-2 at a very higher concentration, presumably potentiating the entry of the SARS CoV-2 spike protein into thyroid cells. 10, 11 This might mediate immunisationinduced damage. In a similar manner, the binding of spike protein to the ACE-2 receptor in endothelial cells induces inflammation of the endothelial cells, with downregulation of ACE-2 leading to a reduction of nitric oxide production and secondary mitochondrial damage. 12 In addition, it is also known that antibodies against the SARS CoV-2 react with cellular antigens including that on the thyroid. 13 Furthermore, the spike protein shows molecular mimicry towards thyroid peroxidase. Thus, the induction of antibodies to COVID-19 may interact with the thyroid surface receptors to cause transient thyroiditis which spontaneously recovers.

Although there is no definitive proof, we note that our patient's symptoms and signs occurred at a time when there is potent immune responsivity, and we suggest a possible cause-and-effect relationship.

Although this is clearly not a major cause for concern in light of the relatively mild illness, and especially at a time when the COVID-19 epidemic is raging and there is high international mortality, we suggest that clinicians should be aware of this putative association with this report of

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