Hyperthyroidism is a common thyroid disease in the endocrine area, the most common cause of which is Graves' disease. Corona Virus Disease 2019 (COVID-19) is the most prevalent and widespread global pandemic in recent times. Since the spread of COVID-19, many countries, such as Singapore and Malaysia, had faced with the infection of JN.1 and other variant strains, and once again had faced a wave of new infections. In autumn and winter seasons, COVID-19 has continued high occurrence. And lower temperatures and drier air in these seasons create conditions favorable for the virus to remain stable for longer periods and spread more easily. Additionally, the convergence of the flu season with the ongoing pandemic adds to the complexity and challenges in controlling the spread of respiratory illnesses. Therefore, continued research in the impact of COVID-19 is essential for enhancing our understanding of the virus and effectively managing future outbreaks.
Previous study shows that 70% of the population was observed to be infected with COVID-19 within three weeks after release of COVID-19 restrictions in China [12], which was pretty close to our data (72.48%). Besides that, there’s a dispute between whether COVID-19 vaccines affect the thyroid function in GD patients, some studies reported that SARS-CoV-2 vaccine may induce new-onset GD [10], while others showed there was no connection [13]. However, our study is the first clinical study to research thyroid function changes in GD patients before and after COVID-19 infection.
A previous study revealed that COVID-19 patients with moderate to critical conditions exhibited higher levels of TSH compared to non-COVID-19 patients. Moreover, COVID-19 patients also experienced a significant increase in TT3 levels during follow-up, while TT4 levels remained mostly unaffected [14]. A combination of retrospective and prospective studies found that serum TRAB levels dropped to a lesser extent following inactivated SARS-CoV-2 vaccination, displaying an upward trend. This phenomenon might be associated with the induced humoral immunity by the vaccination [15]. But currently there is not much research on the impact of COVID on the thyroid function of patients with hyperthyroidism. So, our study is the first to compare thyroid cofunction and metabolic markers in GD patients before and after COVID-19 in China. And our study also mentioned that FT3, FT4, TT3, TT4 and TSAb went up first, then went down after COVID-19 infection.
Previous research suggests that age-related immune function decline, including immunosenescence and inflammaging, plays a significant role in increasing vulnerability to severe COVID-19 outcomes in older adults [16]. Some clinical observations have shown significant lymphopenia and increased neutrophil counts in severe COVID-19 cases. Neutrophil increases may reflect an acute inflammatory response related to the cytokine storm, while lymphopenia indicates significant impacts on cell-mediated immunity in the early stages of COVID-19 [17] [18]. And lymphopenia leads to depletion of both CD4+ and CD8+ T cells, which are crucial for adaptive immune protection, vaccination, and assisting in the production of neutralizing antibodies and direct virus clearance [19]. Several studies have also detected SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 patients [20] [21]. At the same time, CD4 + and CD8 + T cells play a crucial role in GD. Specifically, the production of thyroid-stimulating antibodies is dependent on T cells, and circulating T cells are capable of recognizing multiple epitopes on the TSH receptor [22]. A study exam epigenetic changes in GD by analyzing DNA methylation and histone marks in CD4+ and CD8+ T cells, and found differentially methylated CpG sites in both cell types, with an enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members [23]. Therefore, we speculate that COVID-19 affects the progression of GD by impacting CD4+ and CD8+. However, more research is needed to understand the immune responses to GD patients infected by COVID-19.
There is currently no consensus on the impact of COVID-19 vaccines on thyroid function in patients with hyperthyroidism. Some studies show that vaccine can aggravating hyperthyroidism in patients. A recent systematic review identified a total of 60 cases, including 48 newly diagnosed GD cases and 12 cases of GD recurrence [24]. Notably, twelve patients from a single tertiary institution in Singapore developed hyperthyroidism, either as new-onset GD or relapse of previously well-controlled GD, after receiving the initial dose of SARS-CoV-2 mRNA vaccine [25]. But another study has shown no effect [26]. However, our study showed that COVID-19 vaccine alleviates the fluctuation of immunity caused by COVID-19 in GD patients.
As for whether COVID-19 affects bone metabolism, a randomized, controlled, open-label, platform trial indicates that studies with predominantly poor-quality observational data may suggest a tendency for an association between low serum 25(OH)D levels and COVID-19 related health outcomes [27]. And our data also support the idea that COVID-19 is associated with low bone metabolism in GD patients.
The impact of COVID-19 on GD has significant public health implications. Firstly, GD has created a greater burden on healthcare systems, this has led to resource allocation issues, with some hospitals being forced to prioritize other critical conditions over GD. Secondly, the pandemic has highlighted the need for increased screening and surveillance programs to identify GD early and provide timely treatment. Finally, it has emphasized the need for greater preparedness and response measures to address future pandemics, including ensuring access to telemedicine services and adequate supply chain management. Therefore, understanding these impacts is crucial for developing effective public health strategies to address future pandemics and ensure that patients with autoimmune disease are not left behind.