The present study was approved by the Ethics Committee of the Erciyes University Medical School and informed consent was obtained from the participants.
Sixty-four adults with a history of COVID-19 infection and 70 healthy adults without history of COVID-19 infection were randomly enrolled in the study. COVID-19 survivors were evaluated at a median of 5.7 months (IQR: 4-6.5) (range: 2-7 months) after acute COVID-19 infection. SARS-COV-2 polymerase chain reaction of nasal and oral swab samples was used in the diagnosis of acute COVID-19 infection.
The clinical characteristics of patients (status of oxygen demand, history of intensive care unit (ICU) hospitalization and intubation, treatments used), prognostic markers of COVID-19 (platelet, lactate dehydrogenase level, lymphocyte, ferritin, d-dimer levels, and C-reactive protein) and basic biochemical tests during the course of acute COVID-19 were recorded. The patients were categorized as mild, moderate, and severe/critical disease severity according to the Health Commission of China during acute COVID-19 infection [13]. In mild disease, the symptoms are mild and there is no evidence of pneumonia on radiological examination. In moderate disease, respiratory system symptoms and fever are present and radiological examination may reveal evidence of pneumonia. Severe/critical disease is characterized by the presence of any of respiratory rate ≥30/minute, oxygen saturation ≤ 93%, shock states, more than 50% progression of pneumonic infiltration within 24-48 hours on radiological examination, and need for mechanical ventilation and ICU.
A history of thyroid disease and surgery, neck radiation, pregnancy, use of medication that affects thyroid function, and pituitary/hypothalamic disease, were accepted as the exclusion criteria of the current study.
Blood tests were obtained between the hours 8.00-9.00 for basal biochemical and hormonal investigations, anti-thyroid peroxidase (TPO), anti-thyroglobulin (Tg) antibodies, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and free triiodothyronine (FT3) from the participants. COVID-19 survivors, who had thyroid function tests (TFT) before and during acute COVID-19 infection, were also evaluated retrospectively.
Thyroid hormone levels and thyroid autoantibodies were measured by the electrochemiluminescence immunoassay (ECLIA) method (Mannheim, Germany, Cobas; Roche Diagnostics,). Reference ranges were as follows: TSH = 0.27- 4.20 µU/mL, FT4 = 0.93-1.97 ng/dL, FT3 = 2-4.4 pg/mL, anti-TPO = 0-34 U/ml and anti-Tg = 0-115 U/ml. The titer values of antibodies higher than the upper reference range were considered positive.
Thyroid gland ultrasonography (USG) was performed on all participants by the same physician on the same day with blood tests, with a GE LOGIQ P5 ultrasound machine. Thyroid gland volume was calculated by ellipsoid formula: maximum length (L), width (W), and depth (D) for each lobe (volüme = LxDxWx0.524). Total thyroid gland volume was calculated by summing the volumes of both lobes and if the maximum diameter of the isthmus was more than 5 mm, it was also added [14, 15]. In addition, participants with ≥1 cm nodules in the USG examination were excluded from the study.
Statistical analysis
The data was analyzed in the IBM SPSS program version 22. The Shapiro–Wilk test was used for data distribution. Data with normal distribution were shown as mean ± standard deviation (SD) and data with non-normally distributed were shown as median and interquartile range (IQR). For the comparison of quantitative variables in two independent groups, the Mann–Whitney U test or two independent samples t-tests was preferred according to the distribution of the data. For the comparison of quantitative variables, Chi-square tests were preferred. The COVID-19 disease severity groups were compared among themselves by one-way ANOVA and the Tukey HSD or Games-Howell test was preferred according to data distribution for post-hoc analysis. The correlation analysis was performed by Pearson or Spearman correlation analysis depending on the distribution of the data. The comparison of pre-COVID with post-COVID and acute-COVID with post-COVID data of the same patients was performed by using the Wilcoxon test or student’s T paired test. if the probability (P) value was <0.05, it was considered statistically significant.