Subacute thyroiditis following COVID-19: A systematic review.

Background: Subacute thyroiditis (SAT) is a self-limiting thyroid inflammatory disease occurring specifically after upper respiratory tract infections. Since COVID-19 is a respiratory disease leading to multi-organ involvements, we aimed to systematically review the literature regarding SAT secondary to COVID-19. Methods: We searched Scopus, PubMed/MEDLINE, Cochrane, Web of Science, ProQuest, and LitCovid databases using the terms "subacute thyroiditis" and "COVID-19" and their synonyms from inception to November 3, 2022. We included the original articles of the patients with SAT secondary to COVID-19. Studies reporting SAT secondary to COVID-19 vaccination or SAT symptoms' manifestation before the COVID-19 infection were not included. Results: Totally, 820 articles were retained. Having removed the duplicates, 250 articles remained, out of which 43 articles (40 case reports and three case series) with a total of 100 patients, were eventually selected. The patients aged 18-85 years (Mean: 42.70, SD: 11.85) and 68 (68%) were women. The time from the onset of COVID-19 to the onset of SAT symptoms varied from zero to 168 days (Mean: 28.31, SD: 36.92). The most common symptoms of SAT were neck pain in 69 patients (69%), fever in 54 (54%), fatigue and weakness in 34 (34%), and persistent palpitations in 31 (31%). The most common ultrasonographic findings were hypoechoic regions in 73 (79%), enlarged thyroid in 46 (50%), and changes in thyroid vascularity in 14 (15%). Thirty-one patients (31%) were hospitalized, and 68 (68%) were treated as outpatients. Corticosteroids were the preferred treatment in both the inpatient and outpatient settings (25 inpatients (81%) and 44 outpatients (65%)). Other preferred treatments were nonsteroidal anti-inflammatory drugs (nine inpatients (29%) and 17 outpatients (25%)) and beta-blockers (four inpatients (13%) and seven outpatients (10%)). After a mean duration of 61.59 days (SD: 67.07), 21 patients (23%) developed hypothyroidism and thus, levothyroxine-based treatment was used in six of these patients and the rest of these patients did not receive levothyroxine. Conclusion: SAT secondary to COVID-19 seems to manifest almost similarly to the conventional SAT. However, except for the case reports and case series, lack of studies has limited the quality of the data at hand.

Emerging trends and hot spots in subacute thyroiditis research from 2001 to 2022: A bibliometric analysis.

Background: Subacute thyroiditis (SAT) is the most prevalent self-limiting thyroid disease that causes pain, accounting for about 5% of all clinical thyroid disorders. Numerous clinically noteworthy results have been published in this area over the last 20 years. However, no article has comprehensively assessed the relevant literature yet. We conducted a bibliometric analysis of SAT to provide light on the dynamic nature of scientific advancement and aid researchers in gaining a global perspective while examining research core themes and hotspots. Methods: SAT-related articles and reviews from 2001 to 2022 were retrieved from the Science Citation Index-Expanded of Web of Science Core Collection (WoSCC). We analyzed current research trends and hotspots in this area using CiteSpace and Vosviewer. Results: A total of 568 studies associated with SAT research were published in 282 academic journals by 2,473 authors in 900 institutions from 61 countries/regions. The United States was a crucial link in inter-country/region collaboration and was the most frequently involved country in international cooperation. The University of Missouri System was the top organization, and Braley-Mullen H. was the most productive researcher. Thyroid published the most papers, with 36 publications. The most co-cited article was "Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study" (by Fatourechi V., 2003). The clustered network and timeline view of keywords showed that the prevalence, diagnosis, and treatment of SAT were the research core themes during the past 20 years. Analysis of keyword bursts indicated that the clinical characteristic and the influence of COVID-19 on SAT appeared to be the current research hotspots. Conclusion: This bibliometric analysis conducted a thorough review of the SAT research. The clinical characteristics and the genetic background of SAT under the influence of COVID-19 are current research hotspots. However, there is still a need for further study and global collaboration. Our findings can aid researchers in understanding the current status of SAT research and immediately pinpoint new directions for further investigation.

Evaluation of the diagnostic features and clinical course of COVID-19 vaccine-associated subacute thyroiditis.

OBJECTIVE: This study aimed to identify cases of coronavirus disease 2019 (COVID-19) vaccine-associated subacute thyroiditis (SAT) during the active vaccination period of the pandemic, analyze the characteristics of these cases, and compare them with cases of non-vaccine associated SAT diagnosed in the same period. METHODS: A total of 55 patients diagnosed with SAT in our outpatient clinic between February and October, 2021, were included in this retrospective single-center study. RESULTS: Of the study population, 16 (29.1%) were diagnosed with COVID-19 vaccine-associated SAT (10 with CoronaVac® and six with Pfizer-BioNTech® vaccine), with a median time to onset of symptoms after vaccination of 6.5 (range, 2-20) days. There was no statistically significant difference between the vaccine-associated (VA) and non-vaccine associated (NVA) groups in terms of age, gender, time to diagnosis, thyroid volumes, thyroid function tests, and acute phase reactants. Seven (43.8%) and 25 (64.1%) patients were treated with methylprednisolone in the VA group and NVA group, respectively (p = 0.16). Follow-up data of 45 patients (16/16 for VA and 29/39 for NVA) were available. The mean follow-up of these patients was 47.4 ± 19.4 days, and the follow-up periods of the VA group and NVA group were comparable (p = 0.24). There was no difference between the two groups in terms of the frequency of euthyroidism at the follow-up visit (12/16 vs.14/29, p = 0.08). CONCLUSION: With the increase in COVID-19 vaccination rates during the current pandemic, VA SAT cases are seen more frequently. The present study demonstrated that these cases have similar diagnostic features and clinical course to that of classic forms of SAT. In addition, most patients with VA SAT had a mild clinical course that improved with non-steroidal anti-inflammatory drugs.

Thyroid dysfunction following vaccination with COVID-19 vaccines: a basic review of the preliminary evidence.

PURPOSE: The safety and efficacy of the several types of COVID-19 vaccines, including mRNA-based, viral vector-based, and inactivated vaccines, have been approved by WHO. The vaccines can confer protection against severe SARS-CoV-2 infection through induction of the anti-spike protein neutralizing antibodies. However, SARS-CoV-2 vaccines have been associated with very rare complications, such as thyroid disorders. This review was conducted to highlight main features of thyroid abnormalities following COVID-19 vaccination. METHODS: A comprehensive search within electronic databases was performed to collect reports of thyroid disorders after vaccination with COVID-19 vaccines. RESULTS: Among 83 reported cases including in this review, the most cases of thyroid abnormalities were observed after vaccination with mRNA-based vaccines (68.7%), followed by viral vector vaccines (15.7%) and 14.5% cases following inactivated vaccines. Subacute thyroiditis (SAT) was the most common COVID-19 vaccination-related thyroid disease, accounting for 60.2% of all cases, followed by Graves' disease (GD) with 25.3%. Moreover, some cases with focal painful thyroiditis (3.6%), silent thyroiditis (3.6%), concurrent GD and SAT (2.4%), thyroid eye disease (1.2%), overt hypothyroidism (1.2%), atypical subacute thyroiditis (1.2%), and painless thyroiditis with TPP (1.2%) were also reported. Overall, in 58.0% of SAT cases and in 61.9% of GD cases, the onset of the symptoms occurred following the first vaccine dose with a median of 10.0 days (ranged: 3-21 days) and 10.0 days (ranged: 1-60 days) after vaccination, respectively. Moreover, 40.0% of SAT patients and 38.1% of GD patients developed the symptoms after the second dose with a median of 10.5 days (ranged: 0.5-37 days) and 14.0 days (ranged: 2-35 days) after vaccination, respectively. CONCLUSION: Fortunately, almost all cases with COVID-19 vaccination-associated thyroid dysfunctions had a favorable outcome following therapy. The benefits of COVID-19 vaccinations in terms of terminating the pandemic and/or reducing mortality rates can exceed any risk of infrequent complications such as a transient thyroid malfunction.

Subacute thyroiditis during the COVID-19 pandemic: a prospective study.

PURPOSE: Subacute thyroiditis(SAT) is a destructive thyroiditis associated with viral infections. Several SAT cases associated with SARS-CoV-2 infection/vaccination were recently reported. We aimed to evaluate prospectively all cases applied to our tertiary center and their relationship with SARS-CoV-2 during 16 months of the pandemic. Cases during similar pre-pandemic period were recorded for numeric comparison. METHODS: Prospective study took place between March 2020 and July 2021. SAT was diagnosed by classical criteria. Swabs for SARS-CoV-2 and a wide respiratory viral panel (RV-PCR) were taken. Previous COVID-19 was assessed by SARS-CoV-2 IgM&IgG levels. Study group was divided into three as: CoV-SAT, patients who had or still have COVID-19, Vac-SAT, patients diagnosed within three months after SARS-CoV-2 vaccination and NonCoV-SAT, those not associated with COVID-19 or vaccination. RESULTS: Out of 64 patients, 18.8% (n = 12) was classified as CoV-SAT, 9.3% (n = 6) as Vac-SAT and 71.9% as (n = 46) NonCoV-SAT. SARS-CoV-2 RT-PCR tests on the diagnosis of SAT were negative in all, but two patients tested positive five days later, in second testing, performed upon clinical necessity. CoV-SAT and NonCoV-SAT groups were similar in terms of clinical, laboratory, and treatment characteristics. However, symptoms were milder and treatment was easier in Vac-SAT group (p = 0.006). CONCLUSIONS: Total number of SAT cases during the pandemic period was comparable to pre-pandemic period. However, a considerable rate of SARS-CoV-2 exposure in SAT patients was established. COVID-19 presented with SAT, as the first manifestation in three cases. Vaccine-related cases developed in a shorter time period, clinical presentation was milder, and only a few required corticosteroids.

Incidence of De Quervain's thyroiditis during the COVID-19 pandemic in an area heavily affected by Sars-CoV-2 infection.

PURPOSE: To evaluate the possible association between Covid-19 infection and subacute thyroiditis. METHODS: We reviewed the medical and imaging records of patients referred to our Department's outpatient setting dedicated to 'thyroid emergency' (records with a 'bollino verde'-green sticker, classifed as urgent) from April 2020 to October 2020. This outpatient clinic is devoted to patients requiring evaluation for severe hypothyroidism, thyrotoxicosis and neck discomfort or pain. All patients with a newly-diagnosed subacute thyroiditis were selected. The data of all patients receiving a diagnosis of subacute thyroiditis was collected retrospectively, taking into account the same period of time (April-October) and starting from 2016. RESULTS: During the COVID-19 outbreak in our region (April 2020 to October 2020) 396 patients attended the outpatient emergency clinic. Among them, 10 (2.5%) patients received a diagnosis of subacute thyroiditis. In a single patient, a 44-year-old man, a COVID-19 pulmonary infection had been diagnosed 7 weeks before the diagnosis of subacute thyroiditis. All of the remaining patients were and remain COVID-19 free as confirmed by telephone interview. The percentage of patients who received a diagnosis of subacute thyroiditis in the same period starting from 2016 was very similar (2.9%, 2.9%, 2.6% and 3.0% in 2016, 2017, 2018 and 2019, respectively). CONCLUSIONS: Our data do not show an increase in the incidence of subacute thyroiditis in the Brescia area, a region with the highest prevalence of COVID-19 in Italy during the period of the pandemic outbreak.

Risk factors, treatment and outcomes of subacute thyroiditis secondary to COVID-19: a systematic review.

BACKGROUND: COVID-19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS-CoV-2 as a cause of subacute thyroiditis (SAT). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms 'COVID-19', 'SARS-CoV-2' and 'coronavirus' along with search terms 'thyroiditis', 'thyrotoxicosis' and 'thyroid' were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. RESULTS: Fifteen publications reporting on 17 individual cases of COVID-19-induced SAT were identified. Age ranged from 18 to 69 years. The majority (14 of 17; 82%) of cases were female. The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated C-reactive protein (CRP) was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Antithyroid antibodies were frequently negative. SAT-specific treatment included corticosteroids for 12 of 17 (70.5%) patients. Most returned to normal thyroid status. CONCLUSION: COVID-19-associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross-over of common clinical features between COVID-19 and thyrotoxicosis.

New aspects in the pathogenesis and management of subacute thyroiditis.

Subacute thyroiditis (SAT) is a thyroid inflammatory disease, whose pathogenesis and determinants of the clinical course were unclear for many decades. The last few years have brought many clinically significant new data on the epidemiology, pathogenesis and management of SAT. Several human leukocyte antigen (HLA) alleles were demonstrated not only to increase the risk of SAT, but also to correlate with SAT clinical course and determine the risk of recurrence. The world-wide epidemic of the coronavirus disease 19 (COVID-19) has provided new observations that the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be a potent SAT-triggering factor, and that the clinical course of SAT in patients affected by COVID-19 is different from a typical one. Additionally, many new trends in the clinical course are emerging. In the last years, painless course of SAT is more and more often described, constituting a special challenge in patients hospitalized due to COVID-19. Despite an excellent availability of diagnostic methods, several difficulties in SAT differential diagnosis can be currently encountered and the proper diagnosis and treatment is frequently delayed. False positive diagnoses of SAT in patients with malignancies of poor prognosis constitute a life-threatening problem. Taking into account all the new aspects of SAT pathogenesis and of its clinical course, the new - modified - SAT diagnosis criteria have been proposed.