Incidence of autoimmune thyroiditis following SARS-CoV-2 infection: A retrospective cohort study at Tikrit teaching hospital
2025 年 74 巻 1-2 号 p. 1-4
詳細
2025 年 74 巻 1-2 号 p. 1-4
Emerging evidence suggests a link between COVID-19 and the development of autoimmune conditions, including autoimmune thyroiditis. However, the prevalence and characteristics of this association remain unclear. We aimed to investigate the incidence of autoimmune thyroiditis in patients recovering from COVID-19 and explore the potential demographic and clinical risk factors associated with its development. This retrospective cohort study was conducted at Tikrit Teaching Hospital from March 2021 to January 2024. In total, 780 patients with confirmed COVID-19 were included in this study. Patients with a history of autoimmune thyroid disease were excluded. Medical records were analyzed for evidence of new-onset autoimmune thyroiditis, identified by elevated thyroid autoantibodies (thyroid peroxidase antibodies [TPOAb] and thyroglobulin antibodies [TGAb]) and abnormal thyroid function tests (TFTs) after post-COVID-19 recovery. Demographic information, details of COVID-19, and pre- and post-infection TFTs were extracted and analyzed. Of the 780 patients, 62 (7.9%) developed autoimmune thyroiditis after recovery from COVID-19. This condition was more prevalent in females (67.7% of cases) and was associated with severe COVID-19 infection (p < 0.001). Patients who developed autoimmune thyroiditis exhibited significantly higher levels of TPOAb and TGAb after infection (both p < 0.001). Thyroid function test results indicated marked changes, predominantly showing hypothyroidism. This study provides evidence for a significant association between COVID-19 and the onset of autoimmune thyroiditis, highlighting the need to monitor thyroid function in COVID-19 survivors. Further research is necessary to elucidate the mechanisms underlying this association and identify at-risk patients.
The relationship between coronavirus disease-2019 (COVID-19) and autoimmune diseases, particularly autoimmune thyroiditis, represents a complex interplay between the viral infection and autoimmune mechanisms. This study conducted at Tikrit Teaching Hospital aimed to explore this connection by examining the incidence of autoimmune thyroiditis in patients recovering from COVID-19 infection. Emerging evidence suggests that severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, may trigger autoimmune responses, potentially leading to autoimmune thyroiditis in susceptible individuals4,7,9).
Shah et al.14) and Liu et al.5) provide a foundation for understanding how viral infections, including COVID-19, could exacerbate or initiate autoimmune diseases. The cytokine storm and multisystemic involvement involved in severe COVID-19 highlight the capacity of the virus to induce systemic immune dysregulation. Staruszkiewicz et al.16) discuss the specific impact of SARS-CoV-2 on the thyroid gland and proposed mechanisms through which the virus could directly or indirectly lead to the development of autoimmune thyroiditis.
Findings from the Tikrit Teaching Hospital add to the body of evidence indicating a potential link between COVID-19 and autoimmune thyroid disease. This study underscores the importance of monitoring for autoimmune complications in patients recovering from COVID-19 and highlights the need for further studies to comprehensively elucidate the mechanisms underlying this association. Understanding these mechanisms is crucial for the development of targeted interventions to manage and prevent autoimmune thyroiditis in patients recovering from COVID-19.
This retrospective cohort study analyzed medical records between March 2021 and January 2024. We identified cases of new-onset autoimmune thyroiditis among patients who had recovered from COVID-19 by comparing thyroid function and serum antibody levels before and after the infection. Potential confounders such as critical illness and medication effects on thyroid tests were factored in during the inclusion process.
Accounting for Intrinsic COVID-19 FactorsThe effects of intrinsic factors associated with COVID-19 (e.g. critical illness, medications, etc.) on thyroid function were analyzed and differentiated. Critical illness often results in non-thyroidal illness syndrome (NTIS), which can manifest as altered thyroid function, independent of the actual thyroid pathology. Furthermore, medications used in the treatment of COVID-19, such as high-dose steroids and interleukin inhibitors, may transiently affect thyroid hormone levels.
To address this, thyroid function tests were reassessed after recovery, and only persistent abnormal findings beyond the acute phase of illness and after cessation of COVID-19 specific treatments, were considered indicative of autoimmune thyroiditis. This distinction is crucial to ensure that the observed thyroid dysfunction is not merely a transient response to acute illness or medication.
ParticipantsInitially, 800 patients diagnosed with COVID-19 via reverse transcriptase-polymerase chain reaction (RT-PCR) and treated at the Tikrit Teaching Hospital were considered. After applying the inclusion criteria, 780 adult patients (≥ 18 years) with confirmed COVID-19 and those with preexisting autoimmune thyroid diseases, other chronic autoimmune conditions, or incomplete medical records remained eligible for the study. We also collected data on Body Mass Index (BMI), liver and kidney functions, and metabolic medication use to assess their potential influence on thyroid function outcomes.
Data CollectionData were extracted from patient medical records, including demographic information (age and sex), medical history, details of COVID-19 infection (date of diagnosis, severity of symptoms, and treatment received), and laboratory results. Thyroid function tests (TFTs) including thyroid-stimulating hormone (TSH) and Free Thyroxine (FT4) using the Elecsys Cobas assay kits and thyroid autoantibodies (thyroid peroxidase antibodies [TPOAb] and thyroglobulin antibodies [TGAb] ) were collected before COVID-19 infection (if available) and at follow-up visits post-recovery. The median time from documented COVID-19 recovery to subsequent thyroid function testing was 3 months, ranging from 1 to 6 months.
Definition of Autoimmune ThyroiditisAutoimmune thyroiditis was defined as the presence of elevated thyroid autoantibodies (TPOAb and/or TGAb) above the laboratory reference range in combination with abnormal TFTs results in patients with no prior history of thyroid disease.
Severity of COVID-19 InfectionCOVID-19 severity was categorized based on the clinical symptoms and required interventions as mild (managed at home), moderate (required hospitalization), or severe (intensive care and/or mechanical ventilation).
Statistical AnalysisPatients with transient thyroid abnormalities associated with acute COVID-19 were excluded from the final analysis of autoimmune thyroiditis cases. This helped establish a clear causal relationship between COVID-19 and long-term thyroid dysfunction. Statistical methods were employed to adjust for these confounding factors, ensuring that the reported associations were likely reflective of true autoimmune pathology rather than temporary changes due to illness or medication.
Descriptive statistics were used to summarize the demographic and clinical characteristics of patients. The incidence of autoimmune thyroiditis after post-COVID-19 was calculated. Chi-square and Fisher’s exact tests were used to explore the associations between categorical variables, whereas t-tests were used for continuous variables. Statistical significance was set at p < 0.05. 3. All analyses were performed using SPSS version 26.
Ethical ConsiderationsThe study was approved by the Ethics Committee of the Tikrit Teaching Hospital (approval number EC/TTH/2021-04). All patient data were anonymized to protect privacy, and the study was conducted in accordance with the Declaration of Helsinki.
The study cohort consisted of 429 (55%) males and 351 (45%) females with an age range of 18–85 years. The median patient age was 46 years. The median BMI was 28.3, and Comprehensive liver and kidney function tests were conducted, along with a review of metabolic medications. COVID-19 severity was categorized as mild in 468 (60%) patients, moderate in 234 patients (30%), and severe in 78 (10%) patients. The p values listed for COVID-19 severity compare the proportion of patients with autoimmune thyroiditis across the three severity categories. Statistical analysis demonstrated a significant association between more severe COVID-19 and the incidence of autoimmune thyroiditis (p < 0.001), suggesting that patients with more severe COVID-19 were more likely to develop autoimmune thyroiditis (Table 1).
Demographics and Clinical Characteristics
| Characteristics | Total Patients (n = 780) | With Autoimmune Thyroiditis (n = 62) | Without Autoimmune Thyroiditis (n = 718) | P-value |
|---|---|---|---|---|
| Gender (Female) | 351 (45%) | 42 (67.7%) | 309 (43%) | < 0.01* |
| Median Age (years) | 46 | 50 | 45 | < 0.05** |
| COVID-19 Severity | < 0.001* | |||
| - Mild | 468 (60%) | 28 (45.2%) | 440 (61.3%) | |
| - Moderate | 234 (30%) | 22 (35.5%) | 212 (29.5%) | |
| - Severe | 78 (10%) | 12 (19.4%) | 66 (9.2%) | |
| Median BMI | 28.3 | 27.9 | 28.4 | n.s.** |
| Liver Function Normal | 710 (91%) | 56 (90.3%) | 654 (91.1%) | n.s.*** |
| Kidney Function Normal | 732 (93.8%) | 58 (93.5%) | 674 (93.9%) | n.s.*** |
| Metabolic Medications | 122 (15.6%) | 11 (17.7%) | 111 (15.5%) | n.s.*** |
Analysis Methods: * Chi-square test, ** t-test , *** Fisher’s exact test
Of the 780 patients, 62 (7.9%) were diagnosed with new-onset autoimmune thyroiditis after recovering from COVID-19. The female-to-male ratio was significantly higher (42 [67.7%] females; 20 [32.3%] males) (Table 2).
Comparison of Thyroid Function Tests
| Test | Pre-COVID-19 Mean ± SD | Post-COVID-19 Mean ± SD | P-value | Normal Range (Elecsys cobas kit) |
|---|---|---|---|---|
| TSH (mIU/L) | 2.4 ± 0.9 | 7.1 ± 2.7 | < 0.001* | 0.27–4.20 mIU/L |
| FT4 (ng/dL) | 1.3 ± 0.4 | 0.8 ± 0.3 | < 0.001* | 0.93–1.70 ng/dL |
| TPOAb (IU/mL) | 30 ± 20 | 210 ± 95 | < 0.001* | < 34 IU/mL |
| TGAb (IU/mL) | 25 ± 15 | 160 ± 85 | < 0.001* | < 115 IU/mL |
* Analysis Method: t-test
Marked changes in thyroid function test results and antibody levels were observed in patients who developed autoimmune thyroiditis after post-COVID-19. Among these, 30 cases were identified as subclinical hypothyroidism (normal FT4 and elevated TSH levels), 20 as overt hypothyroidism (low FT4 and elevated TSH levels), and 12 were started on levothyroxine treatment owing to clinical symptoms and laboratory findings. The median time from documented COVID-19 recovery to subsequent thyroid function testing was 3 months, ranging from 1 to 6 months. This timeline was critical for observing the changes in thyroid function post-infection (Table 2).
Statistical Analysis and SignificanceStatistical analysis confirmed significant associations between the development of autoimmune thyroiditis and both the severity of COVID-19 (p < 0.001) and female sex (p < 0.01). Changes in thyroid function and antibody levels before and after COVID-19 were significant (all p < 0.001), indicating a strong link between COVID-19 and autoimmune thyroiditis. No significant association was found between BMI, liver function, kidney function, presence or absence of metabolic medications, and the development of autoimmune thyroiditis. Patients who did not develop autoimmune thyroiditis showed no significant changes in thyroid function post-COVID-19.
Our study revealed a significant association between COVID-19 and the subsequent development of autoimmune thyroiditis. This association was particularly pronounced in patients with severe forms of COVID-19 and was more prevalent among females. These findings align with an emerging body of literature suggesting a link between SARS-CoV-2 infection and various autoimmune conditions, including those affecting the thyroid gland3,6,8,11).
The incidence of autoimmune thyroiditis in our cohort was 7.9%, which was notably higher than the estimated prevalence in the general population, suggesting a potential triggering effect of the virus on autoimmune responses within the thyroid. This is consistent with the observations of Peng et al.10), who reported an increased incidence of autoimmune disorders following COVID-19. Similarly, Scappaticcio et al.13) found a heightened risk of thyroiditis after post-COVID-19, supporting our findings and highlighting the impact of the virus on the respiratory system.
The strong association between severe COVID-19 and the development of autoimmune thyroiditis may be attributed to the ability of the virus to induce a robust inflammatory response that could lead to autoimmunity in genetically predisposed individuals. This is supported by Sher et al.15), who demonstrated a link between systemic inflammatory markers and autoimmune diseases in COVID-19 patients. The virus may disrupt immune tolerance by altering regulatory T cell function or by direct molecular mimicry, where viral antigens resemble self-antigens, thus sparking an autoimmune response. Additionally, the interaction of the virus with ACE2 receptors expressed on thyroid follicular cells can initiate or exacerbate thyroid autoimmunity by direct infection of the gland or through cytokine-induced damage.
Moreover, the predominance of autoimmune thyroiditis among females in our study echoes the sex disparities observed in autoimmune diseases, as discussed by Angum et al.1). Hormonal factors and genetic predispositions may underlie this disparity, warranting further investigation into sex-specific mechanisms of autoimmunity post-COVID-1912).
Our findings also highlight the crucial role of thyroid function monitoring in patients recovering from COVID-19, especially in those with severe infections and females. Early identification and management of autoimmune thyroiditis could mitigate long-term complications and improve quality of life, as suggested by Çabuk et al.2).
In conclusion, our study adds to the growing evidence of the link between COVID-19 and autoimmune thyroiditis, highlighting the need for awareness and monitoring of thyroid function in COVID-19 survivors. Further research is necessary to understand the underlying mechanisms and develop targeted interventions for at-risk individuals.
The authors declare that they have no conflict of interest.
