Abstract and Introduction
Abstract
Context: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has become the most lethal and rapidly moving pandemic since the Spanish influenza of 1918–1920, is associated with thyroid diseases.
Methods: References were identified through searches of PubMed and MEDLINE for articles published from Jan 1, 2019 to February 19, 2021 by use of the MeSH terms "hypothyroidism", "hyperthyroidism", "thyroiditis", "thyroid cancer", "thyroid disease", in combination with the terms "coronavirus" and "COVID-19". Articles resulting from these searches and references cited in those articles were reviewed.
Results: Though preexisting autoimmune thyroid disease appears unlikely to render patients more vulnerable to COVID-19, some reports have documented relapse of Graves' disease (GD) or newly diagnosed GD about 1 month following SARS-CoV-2 infection. Investigations are ongoing to investigate molecular pathways permitting the virus to trigger GD or cause subacute thyroiditis (SAT). While COVID-19 is associated with non-thyroidal illness, it is not clear whether it also increases the risk of developing autoimmune hypothyroidism. The possibility that thyroid dysfunction may also increase susceptibility for COVID-19 infection deserves further investigation. Recent data illustrate the importance of thyroid hormone in protecting the lungs from injury, including that associated with COVID-19.
Conclusion: The interaction between the thyroid gland and COVID-19 is complex and bidirectional. COVID-19 infection is associated with triggering of GD and SAT, and possibly hypothyroidism. Until more is understood regarding the impact of coronavirus on the thyroid gland, it seems advisable to monitor patients with COVID-19 for new thyroid disease or progression of preexisting thyroid disease.
Introduction
COVID-19 is an infectious disease caused by a newly identified non-segmented single-stranded ribonucleic acid (RNA)-β coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is thought to have spread from infected animal species to humans, this leading in turn to person-to-person transmission.[1] COVID-19 has proven to be the most lethal and most rapidly moving pandemic since that of 1918, having caused 2 857 866 deaths as of April 8, 2021. In humans, it affects, inter alia, the respiratory, neurological, cardiovascular, and gastrointestinal systems. The virus is highly contagious, showing in some people high morbidity and mortality mainly due to severe acute respiratory syndrome (SARS) and exaggerated immune response (cytokine storm), leading to sepsis and death.[2]
Although the disease affects all ages, the worst prognosis is seen in the elderly, in individuals with chronic underlying diseases—particularly obesity and diabetes mellitus—and reduced organ reserves, and in those with a particular genetic susceptibility to the virus, allowing it an easy entrance. COVID-19 has had a dramatic impact on daily life, profoundly affecting anxiety levels, the healthcare system, human activity and behavior, and the economy; all of which is proving exceedingly difficult for societies worldwide to cope with.[3]
The spike proteins covering the coronavirus bind to angiotensin-converting enzyme 2 (ACE2) receptors, regulators of the renin-angiotensin-aldosterone system (RAAS), which are present on the epithelial surface of human cells. SARS-CoV-2 recruits a serine protease, TMPRSS2, which facilitates viral protein priming and cytoplasmic entry.[4] SARS-CoV-2 cell receptor (ACE2 receptor) genes are variably expressed in human organs, with the highest expression being in the small intestine, followed by the testis, heart, thyroid, kidney, and lungs, rendering these tissues particularly susceptible to infection.[5] The widespread expression of the ACE2 receptor and its variable density may explain the variety of symptoms and spectrum of organ failure occurring in patients with COVID-19 and other underlying diseases.
The fact that there is an abundance of ACE2 receptors in the thyroid parenchyma may expose the thyroid gland to SARS-CoV-2 infection. Awareness of the potential for resulting thyroid pathology allows the identification of vulnerable patient groups in a timely fashion so that therapeutic intervention and long-term monitoring can be implemented. Additionally, a patient's thyroid status may have a direct impact on the course of COVID-19 due to the impact of thyroid hormone on multiple organs systems, including the cardiovascular and respiratory systems. In addition, given that thyroid abnormalities have been associated with disorders such as diabetes, obesity, kidney, dysfunction, and liver disease and that patients with these conditions are at increased risk for COVID-19 infection,[6] it is possible that an underlying poorly controlled thyroid disorder may aggravate SARS-CoV-2 infection.[7]
The aim of this mini-review is to summarize the current data regarding associations of COVID-19 with hyperthyroidism, with special focus on the potential impact of SARS-CoV-2 as a causal factor in the development of subacute thyroiditis (SAT) and as a trigger or perpetuator of Graves' disease (GD). Associations between COVID 19 and non-thyroidal illness and hypothyroidism will be explored. Moreover, the possibility will also be considered that thyroid dysfunction may be associated with worse COVID-19 outcomes. If this is the case, monitoring of thyroid status in COVID-19 patients, particularly those with preexisting thyroid disease, may be prudent.
J Endo Soc. 2021;5(8) © 2021 Endocrine Society
