Subacute Thyroiditis in the SARS-CoV-2 Era (SAT-COVID-19)

Subacute Thyroiditis in the SARS-CoV-2 Era: a Multicentre Prospective Study

Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up is known. This prospective, longitudinal, 3-year, multicentre study is aimed at exploring clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage.

All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Multicentre study. Data about anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapside was investigated. Patients were evaluated after 1, 3, 6, 12 months.

Study Overview

• Status: Completed
• Conditions: SARS CoV 2 Infection; Subacute Thyroiditis; Thyrotoxicosis
• Intervention / Treatment: Diagnostic test: Blood sample, CRF, thyroid ultrasound

Detailed Description

A multicentre, longitudinal, prospective study was conducted, enrolling all patients diagnosed with SAT at the participating centres between November 2020 and May 2022. The following Italian centres participated: Endocrinology Unit of Azienda Ospedaliero-Universitaria of Modena (Coordinating center); Endocrinology Unit of IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milano; Endocrinology and Diabetes Prevention and Care Unit of the IRCCS Azienda Ospedaliero-Universitaria Policlinico of Bologna. These Units were involved through a call launched by the coordinating center to the young Italian members of the Club EnGioI (Endocrinologia Giovane in Italia) of the Italian Society of Endocrinology (SIE).

Five visits were planned: at diagnosis (V0) and after 1, 3, 6 and 12 months (V1, V2, V3 and V4, respectively). At each visit, subjects were evaluated with anamnesis, physical examination, thyroid ultrasound and blood tests. Patients were treated according to the clinical presentation and to the current guidelines. Nonsteroidal anti-inflammatory drugs (NSAIDs) were preferred in patients with mild symptoms and mild laboratory findings; steroid therapy was preferred in those with severe symptoms and/or those who did not respond to NSAIDs within 1 to 2 weeks. Beta-blockers were prescribed as symptomatic treatment in case of tachycardia. During the follow-up phase, the therapeutic approach and any change of it were recorded.

Finally, the treatment responsiveness and outcomes of transient hypothyroidism, permanent hypothyroidism, or recurrence during the follow-up period were all documented.

• Study Type: Observational
• Enrollment (Actual): 66

Contacts and Locations

Study Locations

• Italy
  • Modena, Italy, 41125
    • University of Modena and Reggio Emilia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects with clinical diagnosis of SAT were enrolled. Diagnosis was made by experienced endocrinologists according to guidelines 2: thyroid tenderness and anterior neck pain, often radiating to ears, jaw, or throat, spreading from one side to the other, low-grade fever, pharyngitis symptoms, fatigue, thyroid slightly enlarged, firm and painful to palpation, ESR or CRP elevation.

Description

Inclusion Criteria:

• clinical diagnosis of subacute thyroiditis
• age ≥ 18 years
• willingness to sign an informed consent

Exclusion Criteria:

• ongoing pregnancy
• alcohol abuse.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Covid +; At baseline, a blood sample was collected and centrifuged for serological analysis. Then, sera were stored at -20°C until the end of the enrolment phase when all samples were centralized at the coordinating center for SARS-CoV-2 IgG measurements. IgG against the spike protein (anti-S IgG) and against nucleocapside (anti-N IgG) were tested. Anti-N IgG increase only after natural infection since the nucleocapsid protein is not contained in the vaccines, while anti-S IgG increase is induced either by vaccination or infection 21. Thus, we subdivided patients according to their serological status: i) group Covid+ included those patients who had both positive anti-S and anti-N IgG demonstrating a contact with SARS-CoV-2 before the diagnosis of SAT; ii) group Covid- consisted of patients with only anti-S IgG positivity (due to vaccine) or negative anti-N/anti-S IgG.	Diagnostic test: Blood sample, CRF, thyroid ultrasound; Five visits were planned: at diagnosis (V0) and after 1, 3, 6 and 12 months (V1, V2, V3 and V4, respectively). At each visit, subjects were evaluated with anamnesis, physical examination, thyroid US and blood tests.
Covid -; At baseline, a blood sample was collected and centrifuged for serological analysis. Then, sera were stored at -20°C until the end of the enrolment phase when all samples were centralized at the coordinating center for SARS-CoV-2 IgG measurements. IgG against the spike protein (anti-S IgG) and against nucleocapside (anti-N IgG) were tested. Anti-N IgG increase only after natural infection since the nucleocapsid protein is not contained in the vaccines, while anti-S IgG increase is induced either by vaccination or infection 21. Thus, we subdivided patients according to their serological status: i) group Covid+ included those patients who had both positive anti-S and anti-N IgG demonstrating a contact with SARS-CoV-2 before the diagnosis of SAT; ii) group Covid- consisted of patients with only anti-S IgG positivity (due to vaccine) or negative anti-N/anti-S IgG.	Diagnostic test: Blood sample, CRF, thyroid ultrasound; Five visits were planned: at diagnosis (V0) and after 1, 3, 6 and 12 months (V1, V2, V3 and V4, respectively). At each visit, subjects were evaluated with anamnesis, physical examination, thyroid US and blood tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
quantification of neck pain at diagnosis	evaluation in a scale from 0 to 10 (10 means maximum pain)	at diagnosis
description of neck pain at diagnosis	localization at right or left side, migrating, radiating to the ears	at diagnosis
duration of neck pain at diagnosis	duration in days	at diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
quantification of neck pain at follow-up	evaluation in a scale from 0 to 10 (10 means maximum pain)	1, 3, 6 and 12 months after diagnosis
description of neck pain at follow-up	localization at right or left side, migrating, radiating to the earsmaximum pain)	1, 3, 6 and 12 months after diagnosis
duration of neck pain at follow-up	duration in days	1, 3, 6 and 12 months after diagnosis
thyroid inhomogeneity at ultrasound	US examination performed by endocrinologists with at least 5 years of experience in US neck examination with a linear probe. SAT-related findings such as inhomogeneity will be evaluated (present or absent)	at diagnosis and after1, 3, 6 and 12 months
thyroid function at diagnosis and follow-up	thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), thyroglobulin antibodies (TgAb), anti-thyroid peroxidase antibodies (TPOAb), thyrotropin receptor antibodies (TRAb)	at diagnosis and after1, 3, 6 and 12 months
thyroid stimulating hormone (TSH) serum levels at diagnosis and follow-up	thyroid stimulating hormone (TSH) serum levels	at diagnosis and after1, 3, 6 and 12 months
free thyroxine (fT4) at diagnosis and follow-up	free thyroxine (fT4) serum levels	at diagnosis and after1, 3, 6 and 12 months
free triiodothyronine (fT3) at diagnosis and follow-up	free triiodothyronine (fT3) serum levels	at diagnosis and after1, 3, 6 and 12 months
thyroglobulin (Tg) at diagnosis and follow-up	thyroglobulin (Tg) serum levels	at diagnosis and after1, 3, 6 and 12 months
thyroglobulin antibodies (TgAb) at diagnosis and follow-up	thyroglobulin antibodies (TgAb) serum levels	at diagnosis and after1, 3, 6 and 12 months
anti-thyroid peroxidase antibodies (TPOAb) at diagnosis and follow-up	anti-thyroid peroxidase antibodies (TPOAb) serum levels	at diagnosis and after1, 3, 6 and 12 months
thyrotropin receptor antibodies (TRAb) at diagnosis and follow-up	thyrotropin receptor antibodies (TRAb) serum levels	at diagnosis and after1, 3, 6 and 12 months

Collaborators and Investigators

• Sponsor: University of Modena and Reggio Emilia

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Endocrine System Diseases; Thyroid Diseases; Hyperthyroidism; COVID-19; Thyroiditis; Thyroiditis, Subacute; Thyrotoxicosis
• Other Study ID Numbers: 1104/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No