ABSTRACT
BACKGROUND: A more severe course of COVID-19 was associated with low levels of Vitamin D (VitD). Moreover in vitro data showed that VitD up-regulates the mRNA of the Angiotensin Converting Enzyme 2 (ACE-2), the SARS-COV-2 receptor in different type of cells. ACE-2 is expressed in several type of tissues including thyroid cells, on which its mRNA was shown to be up-regulated by interferon-gamma (IFN-γ). The aim of the present study was to investigate if treatment with VitD alone or in combination with IFN-γ would increase ACE-2 both at mRNA and protein levels in primary cultures of human thyrocytes. MATERIALS AND METHODS: Primary thyroid cell cultures were treated with VitD and IFN-γ alone or in combination for 24 h. ACE-2 mRNA levels were measured by Real-time Polymerase Chain Reaction (RT-PCR). The presence of ACE-2 on thyroid cell membrane was assessed by immunocytochemistry basally and after the previous mentioned treatments. RESULTS: ACE-2 mRNA levels increased after treatment with VitD and IFN-γ alone. The combination treatment (VitD + IFN-γ) showed an additive increase of ACE-2-mRNA. Immunocytochemistry experiments showed ACE-2 protein on thyroid cells membrane. ACE-2 expression increased after treatment with VitD and IFN-γ alone and further increased by the combination treatment with VitD + IFN-γ. CONCLUSIONS: VitD would defend the body by SARS-COV2 both by regulating the host immune defense and by up-regulating of the expression of the ACE-2 receptor. The existence of a co-operation between VitD and IFN-γ demonstrated in other systems is supported also for ACE-2 up-regulation. These observations lead to an increased interest for the potential therapeutic benefits of VitD supplementation in COVID-19.
Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 Drug Treatment , Humans , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral , SARS-CoV-2 , Thyroid Gland/metabolism , Vitamin D/metabolism , Vitamin D/pharmacology , Vitamins/metabolismABSTRACT
BACKGROUND: COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. PURPOSE: The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. CONCLUSIONS: The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a "cytokine storm" that would, in turn, induce a "non-thyroidal illness". Some specific cytokines and chemokines appear to have a direct role on the hypothalamus-pituitary-thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.
Subject(s)
COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Thyroid Hormones/metabolism , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/etiology , Cytokines/blood , Humans , Thyroiditis/etiology , COVID-19 Drug TreatmentABSTRACT
PURPOSE: SARS-COV-2 is a pathogenic agent belonging to the coronavirus family, responsible for the current global world pandemic. Angiotensin-converting enzyme 2 (ACE-2) is the receptor for cellular entry of SARS-CoV-2. ACE-2 is a type I transmembrane metallo-carboxypeptidase involved in the Renin-Angiotensin pathway. By analyzing two independent databases, ACE-2 was identified in several human tissues including the thyroid. Although some cases of COVID-19-related subacute thyroiditis were recently described, direct proof for the expression of the ACE-2 mRNA in thyroid cells is still lacking. Aim of the present study was to investigate by RT-PCR whether the mRNA encoding for ACE-2 is present in human thyroid cells. METHODS: RT-PCR was performed on in vitro ex vivo study on thyroid tissue samples (15 patients undergoing thyroidectomy for benign thyroid nodules) and primary thyroid cell cultures. RESULTS: The ACE-2 mRNA was detected in all surgical thyroid tissue samples (n = 15). Compared with two reporter genes (GAPDH: 0.052 ± 0.0026 Cycles-1; ß-actin: 0.044 ± 0.0025 Cycles-1; ACE-2: 0.035 ± 0.0024 Cycles-1), the mean level of transcript expression for ACE-2 mRNA was abundant. The expression of ACE-2 mRNA in follicular cells was confirmed by analyzing primary cultures of thyroid cells, which expressed the ACE-2 mRNA at levels similar to tissues. CONCLUSIONS: The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry. Future clinical studies in patients with COVID-19 will be required for increase our understanding of the thyroid repercussions of SARS-CoV-2 infection.