Sex: F
Vaccine: COVID19
Symptoms: Thyroiditis subacute
Clinical narrative: subacute thyroiditis; This is a spontaneous report from a non-contactable consumer or other non hcp. This AER is for "case 3". A 44-year-old female patient received bnt162b2 (PFIZER-BIONTECH COVID-19 VACCINE, Solution for injection), via an unspecified route of administration on an unspecified date (Batch/Lot number was not reported) as dose number unknown, single for COVID-19 immunisation. The patient medical history and concomitant medications were not reported. It was unknown whether the patient was pregnant. The patient experienced subacute thyroiditis on an unspecified date. The time to onset was 2 months. There was no product complaint associated with this case. The outcome of event was not resolved.  The article refers to 29 cases that can be found in table 1 in the article. A safety signal for SAT following COVID-19 vaccination was observed via disproportionality analysis comparing the number of observed reports against the calculated number of expected reports. Disproportionate reporting was observed to be statistically significant for the two mRNA-based vaccines of Pfizer/BioNTech (observed n=18, expected n=3) resulting in a lower 95% limit of the Information Component measure for disproportionality (IC025) of 1.5 and Moderna (observed n=5, expected n=1, IC025 = 0.1). The expected value is based on the total number of reports on the covid-19 vaccines and the proportion of reports that relate to SAT in a regulatory database.  Reports in a regulatory database: Up to 08Jun2021, regulatory databases of individual case safety reports (ICSRs), contained 29 reports of SAT (MedDRA preferred term (PT): thyroiditis subacute) following immunization with the novel COVID-19 vaccines. Furthermore, a regulatory database comprised 50 cases reporting the PT autoimmune thyroiditis and another 50 cases reporting the PT thyroiditis following COVID-19 vaccination up to 08Jun2021. In 30 of the 50 cases reporting the PT autoimmune thyroiditis patients were described to suffer underlying Hashimoto's thyroiditis flaring up after the vaccination. Cases reporting SAT were sent from nine countries. Countries contributing most reports were the (Withheld) (n=9), (Withheld) (n=6), and (Withheld) (n=4). Eighteen (62%) of the 29 reports were for the Pfizer/BioNTech mRNA vaccine, five for the Moderna mRNA vaccine, and six for the AstraZeneca adenovirus vector-based vaccine. Cases were mostly classified as non-serious (62%). In the 11 serious cases, two reported caused or prolonged hospitalization and the other nine medically important conditions as the seriousness criteria. Information on the dose number was available in 19 cases. In 11 cases the SAT occurred after administration of the first dose and in nine cases after the second dose. Time-to-onset (TTO) was observed to be in median three days after the second dose (ranging from 0 to 60 days) compared to a median TTO of six days after the first dose (ranging from 0 to 26 days). Patients experiencing SAT following vaccination were mainly female (n=24; 83%) and five patients were male (17%). Patients's age was reported in 28 cases resulting in a median age of 45 years (range 18 to 67 years). Information about the outcome was available in 22 cases. The outcome was reported as 'not recovered' at the time of reporting in 12 cases (41%), in eight cases it was reported as 'recovered' and in the remaining two cases the outcome was unknown.  Treatment: In seven cases (24%) patients reportedly received pharmacotherapy. In six of the cases corticosteroids (prednisone or dexamethasone) were used to treat SAT and in the remaining case the patient was planned to start antibiotic therapy.  Furthermore, in the recent scientific literature a series of case reports of patients developing SAT associated with COVID-19 infections was published 14-21. Six of the eight published reports concern female patients 14-16, 19-21. In most of the cases the onset of the SAT's symptoms (such as anterior neck pain) was reported around two weeks to one month after COVID-19 infection and the condition usually responded well to corticosteroid treatment. Though there is not much evidence of SAT following immunization in general, a series of case reports on patients developing SAT in association with COVID-19 infection can be found in the recent scientific literature. Inflammatory response, apoptosis, and local damage, direct viral replication, interaction with thyroidal ACE2 receptors, and a potential central mechanism with low TSH level possibly secondary to hypothalamus-pituitary dysfunction have been discussed as potential mechanisms for COVID-19-induced SAT. Since the vaccines included in the analyzed case series do not contain the virus itself in any form (neither live attenuated nor inactivated), but only its genetic material, the hypotheses related to direct viral or post-viral damage seem rather improbable in the current context. However, one case (case 18) reported a viral thyroiditis without further specification and in another two cases may represent confounders. Another possible mechanism could be related to autoimmune reactions. In association with vaccines the concept of the autoimmune or inflammatory syndrome induced by adjuvants, known as syndrome comes to mind. A literature review conducted by (name) and colleagues in 2017 investigated the potential correlation between and thyroidal autoimmune conditions. The authors included a series of case reports of patients developing autoimmune thyroid conditions (SAT, multinuclear giant cell granulomas, and thyrotoxicosis) following immunization with various vaccines (in two cases seasonal influenza vaccine, and H1N1 influenza vaccination in the remaining case) 26. The Pfizer/BioNTech vaccine that was reported as suspected in the majority of the cases in the current case series, does not contain any "classical" adjuvant. However, the nanoparticles used as delivery system of the mRNA were discussed to either code liver or themselves to act as adjuvants. Nevertheless, the role of  as a potential mechanism is undermined by lacking evidence. Another hypothesis could be the induction of autoimmune reactions by molecular mimicry. Even though its relevance for the development of autoimmune thyroid diseases was questioned, results from an in-silico study suggested that it might play a role. Furthermore, limitations of the analyzed data (e.g., underreporting of concomitant medication or underlying conditions due to technical constraints in some reporting systems) must be considered.  Summary/Conclusion: Subacute thyroiditis (SAT) is a typically painful inflammatory condition of the thyroid, potentially causing hyperthyroidism-like symptoms such as tachycardia, agitation, tremor, and hyperhidrosis. It is often associated with viral infections, such as mumps, measles, coxsackie, adenovirus, and influenza A and B infection. A safety signal of subacute thyroiditis following vaccination with the novel mRNA- and vector-based COVID-19 vaccines was found during a screening of the regulatory database of individual case safety reports (ICSRs), a regulatory database on 21Apr2021. By 08Jun021 there were 29 ICSRs reporting SAT following the immunization with COVID-19 vaccines entered in a regulatory database. Most of the reports contained Pfizer/BioNTech's and Moderna's mRNA-based vaccines as suspected. Statistically significant disproportionate reporting was observed for these two vaccines. Eleven reports (38%) were classified as serious and in seven cases (24%) pharmacotherapy of SAT symptoms was reported. In five reports cardiac reactions, such as tachycardia and palpitations, and in three reports hyperthyroidism were co-reported. Since SAT's symptomatology can be confused with other painful oropharyngeal conditions (e.g.: odontalgia) but carries the risk of thyrotoxicosis and therefore the possibility of related cardiac, hepatic, and neuromuscular conditions, patients and health care professionals should be sensitized to consider the possibility of SAT following vaccination with the novel COVID-19 vaccines.  No follow-up attempts are possible, information about lot/batch number cannot be obtained. No further information is expected.