COVID-19 and the possible development of autoimmune thyroid diseases

Abstract

In the midst of continuing coronavirus infection (COVID-19) there has been an increase in the incidence of various autoimmune pathologies. Particular attention to the potential relationship between coronavirus infection and autoimmune diseases is attracted by the positive therapeutic effect of the treatment of severe forms of COVID-19 with drugs used in the treatment of rheumatologically diseases.The results of the study should be the starting point for understanding the mechanisms of possible breakdown of immunological tolerance and the development of autoimmune thyroid diseases.AIM: To assess the risks of developing autoimmune thyroid disease after COVID-19, and to investigate the effect of therapy in the acute period on the possible development of autoimmune thyroid diseases.MATERIALS AND METHODS: This prospective comparative study included patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia (n=41). Patients with COVID-19 were divided into two subgroups: a subgroup of patients who received tocilizumab therapy in acute period (n=10), the second subgroup of patients who received symptomatic therapy during the acute period COVID-19 (n=31).To assess the functional status of the thyroid gland all patients underwent observation of the thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), free thyroxine (T4f), antibodies to thyroperoxidase (Ab-TPO) and antibodies to the TSH receptor (Ab-recTSH).The concentrations of 27 signaling molecules in the blood serum were assessed by the technology of multiplex flow immunoassay using the Bio-Plex Pro Human Cytokine 27-plex Assay kit of cytokines and chemokines: interleukins-1b, -1ra, -2, 4-10, -12, -13, -15, -17 (IL-1b, IL-1ra, IL-2, IL - 4-10, IL-12, IL-13, IL-15, IL-17), Eotaxin, fibroblast growth factor (FGF), granulocyte- macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G -CSF), interferon-gamma (IFN-g), IFNγ-inducible protein 10 (IP-10), monocyte chemotactic protein-1 (MCP-1), also known as monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein -1 (MIP-1a and -1b), platelet growth factor BB (PDGF-bb), Regulated on Activation Normal T-cell Expressed and Secreted (RANTES), tumor necrosis factor-alpha (TNF-a), vascular endothelial growth factor (VEGF).All patients denied the presence of thyroid diseases, palpation of the thyroid gland revealed nodular formations in 5% of patients, and appropriate recommendations were given to patients.RESULTS: The overt hypothyroidism was detected in 2.4% of patients, subclinical - in 7.3% of patients in six months after the onset of coronavirus infection, and also found increased levels of the Ab-TPO in six months after recovery (p = 0.023 - Wilcoxon test). In the group of patients with increased Ab-TPO levels after COVID-19, statistically significantly high levels of IFN-g (p = 0.007), Eotaxin (p = 0.008) were obtained. An increased Ab-recTSH were revealed in the group of patients with severe COVID-19 who did not receive pathogenetic therapy with tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).CONCLUSION: The results of our study and the scientific work of foreign colleagues demonstrate the potential risks of developing autoimmune thyroid diseases after a coronavirus infection. A close relationship was found between changes in the thyroid profile and hyperactivation of the immune system with hyperproduction of pro-inflammatory interleukins in COVID-19. This statement is confirmed by the revealed overt and subclinical hypothyroidism, as well as an increase in Ab- TPO levels in this group of patients after a coronavirus infection (p = 0.023 - Wilcoxon test) with a simultaneous persistent increased levels of some pro-inflammatory cytokines in dynamics, determined by autoimmune thyroiditis.The hypothesis of thyroid tissue damage by pro-inflammatory cytokines during COVID-19, as well as the hypothesis suggesting a protective effect on the development of autoimmune thyroid diseases by therapy with tocilizumab in the acute period were confirmed by increased levels of Ab-recTSH in patients with severe COVID-19 who did not receive tocilizumab in the acute period (p = 0.046 - Mann-Whitney test).