Thyroidal ACE2 protein expression and thyroid function tests in patients with COVID-19: results from a retrospective case series and a prospective cohort study.

BACKGROUND
Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is due to fatal inflammatory responses apart of lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to non-thyroidal illness syndrome (NTI) have been described. Furthermore, Angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland.


OBJECTIVE
To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients that died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFT with the severity of the disease in a prospective cohort study.


METHODS
Thyroid tissue of deceased COVID-19 patients (n=23) were analyzed for histopathology and ACE2 expression by immunohistochemical staining. One hundred and fifty-three patients with confirmed SARS-CoV-2 were evaluated regarding TFT and divided into a severe (intubation, intensive care treatment) and an intermediate group.


RESULTS
Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and TSH was associated significantly with deadly disease.


CONCLUSION
The high percentage of positive ACE2 immunostaining in deceased patients compared to normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L was associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFT is crucial in the treatment of severely ill COVID-19 patients.