We found that the commonness of hypothyroidism among COVID-19 patients was 13.2% of which 60% of the patients were females and 40% were males. In comparison with the Iranian general population, this was higher (13.4% Vs 2.3% ) (22). Therefore, our study supports the available research data that hypothyroidism is more common in Iranian women than men. Also, we found that the general case mortality rate was higher in males than females (57.4% vs 42.6%). This also conforms with the hypotheses that COVID-19 mortality is higher in the male gender (23). Fortunately, among the 493 COVID-19 patients, 338(68.6%) were discharged out of which 294(87.0%) did not have a past medical history of hypothyroidism, and 44(13.0%) patients had a past medical history of hypothyroidism. Approximately 32.3% of patients with pre-existing hypothyroidism expired (66.7% women and 33.3% men). As shown in Table 2, there was no statistically significant difference between expired and discharged groups in patients with hypothyroidism (32.3% vs 67.7%) (p = 0.87). Our findings and hypothesis align with van Gerwen M et al retrospective cohort study on 3,703 patients with COVID-19 in the United States. They reported 6.8% had hypothyroidism and 68.1% of the patients with hypothyroidism needed hospitalization, nonetheless, hypothyroidism was not linked with an increased risk of COVID-19 hospitalization or other worse possibilities such as death compared to the non-hypothyroid cases (24).
In pathogenic COVID-19 infections, various factors determine illness severity, including initial viral titers in the airways, as well as the infected person's age and concomitant diseases(25). Current evidence suggests that people with comorbidities such as diabetes, obesity, heart failure, and kidney failure experience more severe illness than others but there is insufficient evidence for the effects of hypothyroidism on COVID-19 prognosis. According to the pathophysiology, some may hypothesize that prognosis of COVID-19 patients with a history of hypothyroidism, especially Hashimoto's thyroiditis will get worse than the normal population. Our findings do not support this hypothesis and in addition, this hypothesis seems to be in contrast with the findings of Chen M et al. which stipulates that, individuals with COVID-19 had considerably lower TSH and serum total triiodothyronine (TT3) levels than healthy controls and non-COVID-19 pneumonia cases. Furthermore, the severity of the condition was positively linked with the degree of the declines in TSH and TT3 levels. The total thyroxine (TT4) level of COVID-19 patients, on the other hand, was not statistically different from that of the control group. Also, low TSH, T3, and thyrotoxicosis seem to be predictors of poor prognosis in COVID-19 patients, according to Chen T. et al (26). Although alterations in serum TSH and TT3 concentrations could be crucial symptoms of COVID-19's fate, hypothyroidism which is dependent on low fT4 levels may not be implicated directly in the poor prognosis of COVID-19 as compared to thyrotoxicosis (27). Moreover, a comparable study conducted in Iran on 390 COVID-19 admitted patients reported n = 21(5.4%) hypothyroid instances with approximately 90% of the participants being above the age of 50. In terms of hypothyroidism's impact on COVID-19 death rates, n = 60 (15.3%) of total patients and n = 4 (19%) of hypothyroid patients died, with no statistically significant difference between the two sets(19). Thyroid disease (TD) is not known to be related to an increased risk of viral infections in general, nor is there an increased chance of developing more severe COVID-19 disease, according to the British Thyroid Association and the Society for Endocrinology (BTA/SFE) in their joint paper.
COVID-19 elicits a two-phase immune response; in the initial (asymptomatic, pre-incubation) phase the adaptive immune response plays a critical role in its attempt to kill infected epithelial cells and thereby preventing viral replication. Phase two indicates that adaptive immunity fails to remove the virus, and as a result, COVID-19 spreads (28). Moreover, angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV-2, plays a role in the pathogenesis of COVID-19 (29, 30). Accumulating evidence demonstrates that ACE2 expression is present in many endocrine organs, including the pancreas and thyroid gland. As a consequence, the thyroid gland could be a point for a targeted COVID-19 attack (31). Patients with this disease fall into two categories: those who get minor symptoms and recover, and those who acquire severe symptoms and die (32). In normal circumstances, innate immunity's NK cells and adaptive immunity's CD8 positive cytolytic T cells work together to eliminate virus-infected cells. When lymphocyte cytolytic activity is impaired, it leads to prolonged interactions between innate and adaptive immune cells, resulting in a cytokine storm, ARDS, and multi-organ failure. This critical condition is one of the significant causes of fatality in COVID-19 patients (33).
Acute respiratory injury in patients with severe COVID-19 is portrayed by inflammation and tissue damage in the lung tissue, which has been linked to T-helper type 17 (Th17) cell responses, as IL-17 can cause alveolar epithelial cell apoptosis and the advancement of pulmonary fibrosis, affecting the normal alveolar structure, alveolar-capillary gas exchange, and alveolar-capillary gas exchange (34). Increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor (GCSF), interferon-inducible protein 10, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory protein 1, and tumor necrosis factor (TNF) are associated with COVID-19 disease severity, according to Puja Mehta et al(33). The causes of excessive production of these cytokines are thought to induce a dysregulated innate immune response to COVID-19 infection (35). IL-17 is involved in the pathogenesis of both COVID-19 and HT. Based on the results of previous studies, there is a significant increase in serum IL-17 levels in HT patients suggesting a potential role of this cytokine in disease pathogenesis (36).
Interestingly, there are notable reports that are in contrast to our findings. A study discovered that COVID-19 patients with hypothyroidism had a greater in-hospital death rate than COVID-19 patients with euthyroidism. Hypothyroidism, like thyrotoxicosis, but to a lesser level, may have a detrimental impact on COVID-19 results. They added that the degree of COVID-19 appears to be the most important factor of the kind of thyroid injury that occurs. As a result, there's a chance primary hypothyroidism might develop during or after COVID-19(12). Wang W et al also performed a study on eighty-four COVID-19 hospitalized patients which reported common thyroid function abnormalities in patients with COVID-19, especially in severe cases. Within the course of the disease, thyroid dysfunction appeared to vary continuously and recovered steadily and spontaneously. Thyroid malfunction was also found to be linked to viral nucleic acid cleanup time, implying that virus infection and replication seem to be implicated for aberrant thyroid hormones (37). Furthermore, Alice Horisberger et al study showed that the frequency or severity of COVID-19 increased in patients with autoimmune diseases (38). Hariyanto Ti et al also confirmed that the severity of the COVID-19 infection is increased among patients with thyroid disease. Their hypotheses highlighted the critical role played by thyroid hormones in controlling innate immune responses. As a consequence, dysregulation of the innate immune response, as demonstrated by greater neutrophil counts, increased CD14 + monocyte and macrophage counts, reduced NK cell counts, and elevated complement levels were found to be substantially related to severe COVID-19 infections. In addition, individuals with thyroid dysfunction had higher levels of pro-inflammatory cytokines notably TNF- and IL-6 (39).
A limitation of our study is that we did not have access to the patient’s thyroid tests since this is a retrospective study and we used data gathered from electronic medical records which did not make those tests public. Hence, the results could be strongly influenced by differences in the definition of thyroid malfunction, the timing of the dysfunction, and whether or not the problem was treated. Furthermore, when thyroid hormone or anti-thyroid medicines were administered in patients with thyroid dysfunction, thyroid hormone levels could be normal. Nonetheless, there is no direct evidence to indicate a link between COVID-19 severity and thyroid hormone level due to a paucity of reliable data on thyroid hormone levels. Further studies should address the influence of thyroid dysfunction treatment on the prognosis of COVID-19.