Spectrum of thyroid dysfunctions among hospitalized patients with non-critically ill coronavirus disease 2019: A cross-sectional study

Background: Pa�ents with coronavirus disease 2019 (COVID-19) par�cularly cri�cally ill pa�ents may present with various thyroid abnormali�es. However, data regarding thyroid func�on tests (TFTs) among noncri�cal pa�ents with COVID-19 are scarce. This study aimed to assess thyroid func�ons and their associa�ons with the severity of illness among non-crically ill hospitalized pa�ents with COVID-19. Methods: This cross-seconal study assessed TFTs in 87 (aged 18-65 years) RT-PCR-conﬁrmed COVID-19 pa�ents admi�ed to a terary-care hospital in Bangladesh. Diagnosis of non–cri�cal illness and severity (mild, moderate, and severe) were deﬁned by WHO’s interim guidance. Pa�ents having known thyroid dysfunc�ons or taking drugs that may aﬀect thyroid func�ons were excluded from the study. Serum TSH, FT4, and FT3 were measured by chemiluminescent immunoassay. Results: Majority of the pa�ents (72%) had normal thyroid func�on. Among the abnormali�es, the highest frequency was isolated hyperthyroxinemia (12.6%) and the rest were subclinical hypothyroidism (6.9%), subclinical thyrotoxicosis (4.6%), thyrotox-icosis (2.3%), isolated tri-iodothyroninemia (1.1%), and hypothyroidism (1.1%). Serum TSH, FT4, and FT3 levels were similar across


Coronavirus disease 2019 (COVID-19) is a systemic viral
disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its outbreak started in late 2019. 1 It mostly affects the respiratory system causing viral pneumonia and the spectrum of the disease ranges from mild, moderate to severe form, and there is also a critical form of illness. 2 Although the respiratory system shows majority of the manifestations, it has been observed over the past two and half years that it can affect many systems including the endocrine system. 3 The thyroid gland is reported to be involved in COVID-19 owing to the presence of angiotensin-converting enzyme-2 (ACE-2) receptor expression combined with transmembrane protease serine 2 (TMPRESS2) in thyroid follicular cells thereby facilitating SARS-CoV-2 entry and replication inside the cell. 4 The reported prevalence of thyroid dysfunction varies between 13% to 64%, including thyrotoxicosis and hypothyroidism. 5 Thyrotoxicosis is mostly due to thyroiditis and there is a relapse or new onset of Graves' disease. 6,7 The thyroid gland and the entire hypothalamic-pituitary-thyroid (HPT) axis were found to be affected resulting in central hypothyroidism induced by hypophysitis or hypothalamic dysfunction. 8 Thyroid dysfunctions in patients with non-critically ill COVID-19 83

Acute viral illness is associated with abnormalities in
TFTs. Thyroiditis is the common presentation with elevated free thyroid hormones and suppressed TSH levels. However, autoimmune thyroid diseases may also flare up. 15 Similarly, several studies show thyroid dysfunctions following SARS-CoV-2 infection and our study also found a spectrum of different abnormalities in thyroid hormone levels. However, majority of the patients (72%) were found to be euthyroid. This is similar with studies by other researchers who also found that most of the patients (>80%) were euthyroid.
They found mild thyroid dysfunctions in smaller percentages (10% -15%). 10,16 This might be explained by the fact that thyroid dysfunction takes time to develop in the course of COVID-19 but it was tested early in this study. 16 Among thyroid dysfunctions, the prevalence of thyrotoxicosis is reported to be common. A retrospective study evaluating 287 patients in Italy found 20.2 % had thyrotoxicosis though prevalence was found lower in other European countries (0.7%) and the USA (0.5%). 17 The prevalence of hyperthyroidism and subclinical hyperthyroidism in Bangladesh was less than one percent (regional study) for each in the general population. 18 We found relatively higher percentages of thyrotoxicosis and subclinical hyperthyroidism, 2.3% and 4.6%, respectively. We recruited the patients before getting steroids; our patients did not receive heparin.
Therefore, low TSH is not due to steroids or elevated FT4 not by heparin due to displacement of the thyroid hormone from the binding proteins. This suggests true thyroid dysfunctions in COVID-19 patients, not drug interference. 19,20 In our study, 12.6% of patients had hyperthyroxinemia,   Although other researcher found a significant negative correlation between TSH and C-reactive protein, which became more pronounced between mild and moderate disease severity and less pronounced between moderate and severe disease severity, there was no significant correlation between TSH and the inflammatory marker C-reactive protein in any group of COVID-19 in our study. 7

Limitations
The limitations of our study were the lack of follow-up data, and we could not measure antibody status, thyroid uptake and scan to find out the etiology.

Conclusion
More than one-fourth non-critical COVID-19 patients