The role of systemic immune activation in the development of thyroid dysfunction in COVID-19

Background. The research of cytokine-induced thyropathies in the midst of continuing coronavirus infection (COVID-19) pandemic is a very important and urgent problem. On the one hand, COVID-19 is often accompanied by a massive overproduction of cytokines, so we can expect an enhanced cytokines effects impact on the thyroid gland. On the other hand, it is possible that biological therapy with tocilizumab, which has a powerful immunosuppressive effect, plays a protective role to the development of cytokines-induced thyropathies amidst COVID-19. The results of the study should be the starting point for understanding the mechanisms of possible compromise of thyroid function during COVID-19.

Aim. The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, FT3 and FT4 values, and patient survival.

Materials and methods. This retrospective, single-center study included 122 patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, FT3, FT4, antibodies to thyroid peroxidase, antibodies to the TSH receptor (AT-recTSH). The markers of the inflammatory process were assessed: interleukin-6, C-reactive protein, the degree of lung tissue damage according to multispiral computed tomography of the lungs, the percentage of blood oxygen saturation (SpO₂), the treatment outcomes.

Results. Five (4%) patients were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with interleukin-6 (r=-0.221; p=0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p=0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99].

Conclusion. Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. This study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate.