The present study provides the first demonstration that the mRNA of the SARS-COV-2 receptor, ACE-2 is expressed in thyroid cells. In addition, by comparing the expression levels of ACE-2 mRNA with those of two reporter genes (GAPDH and β-actin), it was observed that the ACE-2 mRNA is abundantly expressed by thyroid cells.
Several studies highlighted that SARS-COV-2 enters the host cells through ACE-2 receptor, a mandatory step for viral replication and transmission [13, 26, 27]. Based on these findings, the expression pattern of ACE-2 mRNA in specific cell types could identify further routes of SARS-CoV-2 infection in humans. Recent studies have shown that SARS-CoV-2 infection not only affects the upper respiratory tract cells, but also involves other organs. Indeed, SARS-CoV-2 was detected in a variety of human tissues belonging to the respiratory, cardiovascular, digestive, urinary and reproductive systems [28, 29]. ACE2 mRNA was found to be expressed in spermatogonia, as well as Leydig and Sertoli cells, thus suggesting that testis may be potentially vulnerable to SARS-CoV-2 infection. Similarly, Jing et al. suggested that SARS-Cov-2 may infect the ovary, uterus, vagina and placenta through the ubiquitous expression of the ACE-2 receptor . ACE-2 expression was also demonstrated in endothelial cells from arterial and venous vessels . More importantly, there is clear-cut evidence that endothelial cells are prone to acquire SARS-CoV-2 infection , with subsequent development of endotheliitis, endothelial cell damage, systemic vasculitis and disseminated intravascular coagulation.
To provide evidence on whether the thyroid might be a target organ of SARS-COV-2 infection, the present study aimed at identifying ACE-2 in thyroid cells. RT-PCR analysis showed that the ACE-2 mRNA is expressed at consistent levels in thyroid tissue specimens and cells. These findings are in line with data from previous in silico studies. The detection of the mRNA encoding for ACE-2 in thyroid tissue is for sure a relevant finding. However, immunohistochemical studies will be required to confirm that the ACE-2 protein is present on thyroid cells. The expression level of the ACE-2 mRNA in the thyroid were not compared with that in other organs. However, previous data  suggest that expression level of the ACE-2 mRNA in the thyroid, even if relevant, is lower than that in lung, small intestine and colon, and higher than that in breast, liver and skeletal muscle. Further studies, specifically designed to compare the relative expression of the ACE-2 mRNA in different human tissues, will be needed to further clarify this issue.
Taken together, the above described data support the view that the presence of the viral receptor correlates with the susceptibility to SARS-CoV-2 infection and that the receptor expression in tissues other than the lung may explain the multi-organ failure observed in severe cases . As far as the thyroid gland is concerned, Li et al. first reported the expression of ACE-2 in the thyroid, but this was done only by in silico prediction analysis . Our results demonstrate for the first time the expression of ACE2 mRNA in human thyroid surgical specimens and in primary cultures of thyroid cells. It should also be highlighted that, by comparing the expression of ACE-2 mRNA with two different transcripts such as GAPDH and β-actin, the ACE-2 mRNA was found to be abundant and, more importantly, homogenously expressed by thyroid cells.
It is important to note that, as recently demonstrated, SARS-CoV-2 infection requires the ACE-2 receptor to coexist with type II serine protease trans-membranes (TMPRSS2) . TMPRSS2 expression was not evaluated in the present study. However, as recently reviewed by Lazartigues et al., in silico studies indicate that thyroid tissues, with no gender difference, exhibit a high expression of the TMPRSS2 mRNA .
The results of the present study suggest that the thyroid might be vulnerable to SARS-CoV-2 infection. This would fit with the recent clinical descriptions of COVID-19-related SAT [17,18,19,20]. It is interesting to remember that thyroid repercussions were also described during the 2002 outbreak of SARS-CoV [17, 23]. The expression of ACE-2 was related to the SARS coronavirus aggression in other endocrine glands. In particular, Yang et al.  reported that ACE-2 is expressed in the endocrine pancreas, which, after being infected by the SARS coronavirus, undergoes islet damage and impaired insulin release. More recently, Liu et al.  showed that some patients with COVID-19 disease experience pancreatic injury leading to insulin deficiency.
In conclusion, the results of the present study clearly indicate that the mRNA encoding for the ACE-2 receptor is expressed in follicular thyroid cells, making them a potential target for SARS-COV-2 entry. Future clinical studies in patients with COVID-19 will be required to improve our understanding of the thyroid repercussions of SARS-CoV-2 infection.