COVID-19 is an infectious disease that has caused a global pandemic. As a novel disease type with high contagiousness and mortality, the pathophysiology of COVID-19 is not yet fully understood. A number of studies have reported severe and complex effects of COVID-19 on multiple human organs and systems, including immune, respiratory, circulatory, digestive, hepatic, renal, and hematological systems
[14]
. However, the influence of the COVID-19 virus on thyroid hormone levels and the underlying mechanisms are still unclear. Here, we investigated thyroid hormone levels among unvaccinated COVID-19 positive and vaccinated COVID-19 negative people during pre-and post-vaccination. Our study samples randomly selected healthy controls (Group A), unvaccinated COVID-19 positive (Group B), and vaccinated COVID-19 negative (Group C) patients. We found that patients from group B presented with significantly higher levels of TSH and lower levels of TT4 than healthy subjects. However, the levels among groups were within the normal range. We also observed that the TT3 level was significantly lower in the Group B patients than in the control group. These criteria mimic the pattern observed in patients with the non-thyroidal disease (NTI).
Non-thyroidal disease syndrome presents as abnormal thyroid function in serious diseases other than thyroid disease, including severe infections, cardiovascular and gastrointestinal diseases, severe diabetic complications, malignant tumors, severe malnutrition, burns, and trauma
[15]
. It is well established that NTI is a consequence of an acute phase response to macronutrient restriction or severe systemic disease, and the most typical alterations are decreased plasma triiodothyronine (T3) level, normal or low plasma thyroxine (T4) level, and standard or slightly decreased TSH level
[15, 16]
. The decreased T3 and normal TSH phenomenon in COVID-19 patients was consistent with NTI. On the other hand, some cases of post-vaccination thyroid complications have been observed after the administration of different types of COVID-19 vaccines
[4, 17–20]
. Some studies reported subacute thyroiditis following COVID-19 vaccination
[4, 20]
. Similarly, Vera-Lastra et al. reported two cases of Grave’s disease three days after SARS-CoV-2 vaccination
[18]
, and they mentioned that adjuvants might induce the disorder. However, in our study, Group C showed normal thyroid hormone levels, which is in contrast to the above mentioned case studies. One of the possible explanations may be that most of the complications were observed immediately after vaccination. Since our study samples were taken with a time intervals, hormone levels could return to normal.
We continued our further analysis of thyroid functions between the Group B and C at 1, 3, and more than 5 months. Interestingly, the TSH, TT3, and TT4 levels showed fluxes ranging from low to high and vice-versa from day 30 to day above 150 compared to the healthy control, and levels were almost within the borderline ranges after days 150 or above. Wang et al. conducted their study on seven patients who had lower than normal TSH and TT3 levels upon admission, which became normalized by day 30. In addition, the malfunctional feedback between TT3 and TSH returned to work overtime
[21]
. A recent case report of thyroiditis after SARS-CoV-2 infection came from Brancatella et al. confirmed this hypothesis. That case presented thyroid dysfunction followed by a triphasic course, including hypothyroidism, thyrotoxicosis and euthyroidism, and then recovered to normal within a month
[22]
. Two other studies from China and Italy found lower TSH levels in more severely affected patients with COVID-19 and thyrotoxicosis, respectively, after a confirmatory diagnosis of COVID-19, but all thyroid function tests returned close to baseline at follow-up in both Chinese and Italian studies
[10, 23]
. Changes in iodothyronine deiodinase levels, TSH secretion, binding of thyroid hormone to plasma proteins, transport of thyroid hormone to peripheral tissues, and changes in thyroid hormone receptor activity are thought to all likely contribute to the changes in serum levels of thyroid hormone in COVID -19 patients, but this needs further investigation
[24]
.
Moreover, the correlation analysis by Wang et al. initially observed a positive pattern that changed to a negative one over time, although the p-values were statistically insignificant
[21]
. In our present study, we also analyzed the correlation of TSH with TT3 in Group B and C, and found that the TSH and TT3 levels shifted from no association pattern to a negative pattern in Group B. However, given limited number of patients, the p-values did not reach statistical significance. On the other hand, in Group C, a highly significant negative correlation was observed between TSH and TT3 at days above 150, though a minor fluctuation of weak correlation was detected at day 90. These features indicated a recovery of the pituitary-thyroid axis.
This study had some limitations. One was a small number of sample sizes, and random sample collection could introduce potential bias. Second, the types of vaccines that could help us more accurately assess post-vaccination efficacy were not evaluated. For a precise result, a good number of samples and long-term follow-up is recommended.