ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto’s Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (p = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (p < 0.001 and p = 0.005). Hemoglobin levels also increased after COVID-19 infection (p = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (p = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.
KEYWORDS: COVID-19, hypothyroidism, Hashimoto Thyroiditis, thyroid function tests, clinical chemistry tests, COVID-19 vaccines
Introduction
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus disease 2019 (COVID-19), has garnered global attention due to its significant impact on public health. This virus primarily infects human cells by attaching to angiotensin-converting enzyme 2 (ACE2) receptors, spreading through respiratory droplets during coughing or exhaling [1]. Importantly, ACE2 receptors are present in various endocrine organs, particularly the thyroid, a crucial gland for regulating physiological metabolism and maintaining the normal function of multiple systems, organs, and tissues [2]. Given this, a growing interest has emerged in exploring the potential link between SARS-CoV-2 infection and thyroid function.
A case report documented a patient with normal thyroid function and imaging one month prior to contracting COVID-19, who subsequently developed subacute thyroiditis [3]. In an initial cohort of 50 moderate to severe COVID-19 patients, 56% were found to have decreased levels of thyroid-stimulating hormone (TSH). Both their TSH and total triiodothyronine (TT3) levels were lower compared to those of the healthy control group and patients with non-COVID-19 pneumonia [4]. A follow-up study reported that 10.8% of the 287 COVID-19 patients in Italy with severe illnesses developed overt hyperthyroidism [5]. These findings suggest that SARS-CoV-2 infection may have significant impacts on thyroid function.
Given the potential impact of SARS-CoV-2 infection on thyroid function, this study particularly focuses on hypothyroidism, a systemic metabolic syndrome caused by various factors leading to low levels of thyroid hormones or resistance to them [6]. Primary hypothyroidism, resulting from thyroid gland pathology, accounts for over 95% of all cases, with Hashimoto’s Thyroiditis (HT) being the primary cause [7]. HT is an autoimmune condition where the immune system mistakenly attacks the thyroid tissue, causing thyroid damage and a gradual decrease in thyroid hormone production [8]. Less frequent contributors include drug-induced factors, surgical interventions, and other miscellaneous causes.
In this study, we conducted a comprehensive investigation into the modifications in functional status and clinical indices among hypothyroid patients, assessing their status both before and at one month (day (D) 30) and three months (D90) post-SARS-CoV-2 infection. We retrospectively gathered data from the period beginning in the mid-to-late December 2022 timeframe, which overlapped with the onset of the Omicron outbreak in Shanghai. This outbreak was precipitated by the Chinese government’s implementation of the “10 new measures” on 7 December 2022, marking a transition away from the Zero-COVID approach, in alignment with the WHO’s recommendation for a long-term management approach to the COVID-19 pandemic [9].
Materials and methods
Patient cohort and study design
The data for this study on hypothyroid outpatients were retrospectively gathered from the electronic health records at the Thyroid Disease Center (TDC) in Shanghai General Hospital. Informed written consent was obtained from all participants, adhering to the principles outlined in the Declaration of Helsinki. The study was approved by the ethics committee of Shanghai General Hospital.
The study’s index period was established from 1 November 2022, to 30 April 2023. During the screening process, patients under 18 years old, those with autoimmune diseases aside from HT, individuals taking medications known to potentially impact thyroid function (such as systemic corticosteroids, amiodarone, and heparin), and patients who failed to complete the COVID-19 questionnaire were excluded. Ultimately, a total of 164 participants were enrolled. Based on the questionnaire responses, 136 participants were confirmed to have been infected with COVID-19. Further exclusions were made for patients with incomplete datasets or who had adjusted their thyroid medication within one month prior to or three months after their COVID-19 infection. As a result, a total of 128 participants met all the inclusion criteria and were divided into two groups: the HT group and the non-HT group. Based on the timing of the patients’ COVID-19 infections, laboratory data from routine blood examination samples were collected for the final cohort, encompassing pre-infection, as well as D30 and D90 post-infection periods (Figure 1).
Figure 1.
Flowchart of the patient-selection process and study design.
Abbreviations: TDC, thyroid Disease Center; COVID-19, Coronavirus disease 2019; D30, within 30 days post COVID-19 infection; D90, within 90 days post COVID-19 infection.
Collection of clinical and laboratory data
The clinical data comprehensively covered patients’ demographics, including age, gender, smoking and alcohol consumption habits, body mass index (BMI), as well as co-existing medical conditions such as hypertension, diabetes, and stroke.
All laboratory parameters were assessed using early morning fasting venous blood samples collected prior to the administration of Levothyroxine. Thyroid function tests, conducted via the electrochemiluminescence immunoassay method, encompassed measurements of TSH, FT3, free thyroxine (FT4), TT3, total thyroxine (TT4), thyroglobulin (Tg), TgAb, and TPOAb. Additional laboratory findings included haemoglobin concentration (Hb), lactate dehydrogenase (LDH), low-density lipoprotein cholesterol (LDL), lipoprotein (a) [Lp(a)], and 25-hydroxyvitamin D3 (25-OH-D3). All laboratory tests were executed in adherence to the standard procedures of the Laboratory Medicine Department at Shanghai General Hospital, which holds accreditation from the China National Accreditation Service for Conformity Assessment (CNAS).
COVID-19 questionnaire
An online COVID-19 questionnaire was conducted, primarily disseminated through the web link (https://www.wjx.cn/vm/tjXAjGs.aspx) via China’s most popular instant messaging app, WeChat, on social media channels. The survey covers COVID-19 infection status, symptoms experienced, and vaccination history. A positive COVID-19 status was determined by a rapid antigen test (RAT) kit or nucleic acid test (NAT) result [10]. All vaccinated individuals received the intramuscular inactivated vaccine, produced by Sinovac Life Sciences (Beijing, China), the Beijing Institute of Biological Products (Beijing, China), and the Wuhan Institute of Biological Products (Wuhan, China). The vaccine comprised 0.5 mL of inactivated SARS-CoV-2 virus per dose (equivalent to 600 SU), formulated with aluminium hydroxides as an adjuvant.
Statistical analysis
Data were presented as mean ± standard deviation (SD), median with interquartile range (IQR), or number with percentage as appropriate. To identify the predictive factors associated with the persistence of clinical symptoms at D30 and D90 after infection, we employed chi-square test or Fisher’s exact test for categorical variables, Student’s t-test or Mann-Whitney test for quantitative variables, and one-way analysis of variance (ANOVA) to examine inter-group differences. Two-sided p-values <0.05 were considered statistically significant. All statistical analyses were conducted using Prism software (GraphPad Software) and IBM SPSS Statistics version 27.0.1.
Results
The incidence of COVID-19 infection in vaccinated patients was lower
We retrieved and screened 164 patients with a history of hypothyroidism. Of these, 136 had been infected with COVID-19, while 28 had not. Among the infected individuals, 100 were vaccinated. The incidence of COVID-19 infection was lower in vaccinated patients compared to unvaccinated patients (81.30% vs. 87.80%). However, this difference was not statistically significant (p = 0.423) (Figure 2).
Figure 2.
Incidence of COVID-19 infection by vaccination status.
Baseline characteristics of participants
Among the 128 outpatient participants ultimately enrolled, we compared the baseline characteristics and COVID-19 infection symptoms between those in the HT group and those in the non-HT group, as summarized in Tables 1 and 2. Notably, patients in the HT group exhibited a significantly higher BMI compared to those in the non-HT group (p = 0.032). Conversely, individuals in the non-HT group were more likely to smoke and have hypertension, with statistical significance observed at p = 0.011 and p = 0.018, respectively. The proportions of patients with diabetes and stroke were comparable between the two groups. Furthermore, the vaccination rate against COVID-19 was lower in the HT group compared to the non-HT group, with vaccination rates of 67.69% and 85.71%, respectively (p = 0.016). After adjusting for COVID-19 vaccination status, our analysis revealed that HT patients were more prone to experiencing sore throat (p = 0.021) and cough (p = 0.014) as post-infection symptoms. However, no statistically significant differences were observed between the HT and non-HT groups in terms of fever (p = 0.276), dyspnoea (p = 0.621), diarrhoea (p = 0.710), muscle pain (p = 0.156), loss of taste and smell (p = 0.801), or tachycardia (p = 0.440), as detailed in Table 1. In terms of laboratory indicators, the primary difference observed between the HT and non-HT groups was in the levels of TgAb and TPOAb (Table 2).
Table 1.
Comparison of fundamental clinical parameters in HT group versus non-ht group.
| Characteristics | HT (n = 65) | Non-HT (n = 63) | p value |
|---|---|---|---|
| Age (years) Sex, male Alcohol consumption Smoking BMI (kg/m2) |
42.2 ± 12.1 14 (21.54) 10 (15.38) 12 (18.46) 23.25 ± 2.40 |
48.6 ± 14.5 17 (26.98) 18 (28.57) 25 (39.68) 21.61 ± 3.21 |
0.827 0.539 0.088 0.011 0.032 |
| Pre-existing morbidities | |||
| Hypertension Diabetes Stroke Covid-19 vaccines received |
12 (18.46) 10 (15.38) 5 (7.69) 44 (67.69) |
24 (38.10) 14 (22.22) 11 (17.46) 54 (85.71) |
0.018 0.370 0.114 0.016 |
| Covid-19 Infected symptoms | |||
| Fever (>38°C) Dyspnea Diarrhea Sore throat Cough Muscle pain Loss of taste or smell Tachycardia |
27 (21.09) 11 (57.89) 21 (16.41) 26 (20.31) 36 (55.38) 19 (29.23) 10 (15.38) 5 (8.97) |
20 (15.63) 8 (12.70) 23 (17.97) 13 (10.16) 21 (33.33) 9 (14.29) 8 (12.70) 2 (3.17) |
0.276a 0.621a 0.710a 0.021a 0.014a 0.156a 0.801a 0.440a |
This table compares the fundamental clinical characteristics and COVID-19 infected systems of patients in two groups (HT group versus non-HT group). Significant p values are indicated in bold. Data are presented as mean ± SD, median (IQR), number (%) as appropriate.
aCovid-19 vaccines received status is adjusted.
Abbreviations: HT, Hashimoto’s Thyroiditis; non-HT, not Hashimoto’s Thyroiditis; BMI, body mass index.
Table 2.
Comparison of fundamental laboratory characteristics in HT group versus non-ht group.
| Characteristics | HT (n = 65) |
Non-HT (n = 63) |
p value |
|---|---|---|---|
| Thyroid functional indexes | |||
| TSH (µIU/mL) FT3 (pmol/L) FT4 (pmol/L) FT4 (pmol/L) TT4 (ng/ml) Tg (ng/ml) TgAb (IU/ml) TPOAb (IU/ml) |
2.32 ± 1.30 4.96 ± 1.39 16.65 ± 4.70 2.05 ± 0.41 126.90 ± 37.47 2.00 (0.04,19.80) 102.00 (19.25, 377.00) 172.70 (148.75, 201.18) |
1.97 ± 1.29 5.16 ± 1.40 16.68 ± 3.75 2.25 ± 0.66 121.21 ± 24.49 3.17 (0.53, 14.10) 13.95 (12.40, 20.73) 8.28 (8.28, 9.06) |
0.133 0.424 0.965 0.062 0.353 0.406 0.0004 <0.0001 |
| Clinical indexes | |||
| Hb (mg/dL) LDH (IU/L) LDL (mmol/L) lp(a) (mg/dl) 25-OH-D3 (mmol/L) |
13.61 ± 1.38 172.70 (148.75, 201.18) 3.12 ± 1.16 58.80 (47.46, 234.30) 47.39 (40.07, 56.07) |
13.47 ± 1.44 168.20 (148.62, 198.63) 3.01 ± 1.38 69.90 (50.58, 264.49) 42.84 (32.45, 54.43) |
0.689 0.658 0.737 0.641 0.548 |
This table compares the fundamental laboratory characteristics of patients in two groups (HT group versus non-HT group). Significant p values are indicated in bold. Data are presented as mean ± SD and median (IQR) as appropriate.
Abbreviations: HT, Hashimoto’s Thyroiditis; non-HT, not Hashimoto’s Thyroiditis; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TT3, total triiodothyronine; TT4, total thyroxine; Tg, thyroglobulin; TgAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody; Hb, haemoglobin concentration; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; lp(a), lipoprotein (a); 25-OH-D3, 25 hydroxyvitamin D3.
Alterations in thyroid function at D30 and D90 post-covid infection
Overall, we analysed the dynamic changes in thyroid function following COVID-19 infection in hypothyroid patients (Figure 3, Supplementary Table S1). The results from the HT group showed a significant decrease in TSH levels at D90 post-COVID-19 infection (p = 0.013). Conversely, FT3 levels increased significantly at both D30 and D90 post-infection compared to pre-infection levels (p = 0.005 and p < 0.001, respectively). No statistically significant differences were observed in FT4, TT3, TT4, TPOAb, Tg, or TgAb values, as depicted in Figure 3a.
Figure 3.
Alterations in thyroid function post COVID-19 infection.
Thyroid function of patients in two groups, (A) HT group and (B) non-HT group was compared to identify alterations before.
Abbreviations: D30 and D90. PRE, prior to COVID-19 infection; D30, within 30 days after COVID-19 infection; D90, within 90 days after COVID-19 infection; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TT3, total triiodothyronine; TT4, total thyroxine; Tg, thyroglobulin; TgAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody. Significance indicated by the asterisks (p value: *, < 0.05; **, < 0.01; ***, < 0.001.)
For patients in the non-HT group, there was a statistically significant increase in FT3 levels at D90 post-infection compared to pre-infection levels (p < 0.017). However, no significant changes were observed in TSH, FT4, TT3, TT4, TPOAb, Tg, or TgAb values, as illustrated in Figure 3b.
Comparison of thyroid function changes in vaccinated and unvaccinated groups
We further analysed the dynamic alterations in thyroid function, considering the COVID-19 vaccination status. Within the HT group, unvaccinated patients exhibited a significant increase in TSH levels at 90 days post-COVID-19 infection (p = 0.031) compared to pre-infection levels. Additionally, there was an elevation in FT3 levels at both D30 and D90 post-COVID-19 infection (p = 0.012 and p = 0.001, respectively). In contrast, patients who had received the COVID-19 vaccine showed relatively stable thyroid function throughout the pre- and post-infection periods, as illustrated in Figure 4(a).
Figure 4.
Comparison of alterations in thyroid function post COVID-19 infection according to COVID-19 vaccine status.
Thyroid parameters change of the two groups of patients, (A) the HT group and (B) the non-HT group at D30 and D90 were compared based on their COVID-19 vaccination status.
Abbreviations: PRE, prior to COVID-19 infection; D30, within 30 days after COVID-19 infection; D90, within 90 days after COVID-19 infection; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine; TT3, total triiodothyronine; TT4, total thyroxine; Tg, thyroglobulin; TgAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody. Significance indicated by the asterisks (p value: *, < 0.05; **, < 0.01; ***, < 0.001).
In the non-HT group, unvaccinated patients displayed an increase in FT3 levels at 90 days post-COVID-19 infection compared to pre-infection levels (p = 0.040). Consistent with the findings in the HT group, patients who had received the COVID-19 vaccine exhibited stable thyroid function before and after infection, as illustrated in Figure 4b. For further details, please refer to Supplementary Table 2.
Alterations in clinical profiles post COVID-19 infection
We also investigated the dynamic alterations in clinical parameters following COVID-19 infection (Figure 5, Supplementary Table 3). Patients in the HT group demonstrated higher levels of Hb compared to their pre-infection levels (13.96 mg/dL vs. 13.61 mg/dL, p = 0.033). However, no significant changes were observed in other clinical indicators, as illustrated in Figure 5a. Similarly, no statistically significant changes were noted in the non-HT group, as shown in Figure 5(b).
Figure 5.
Alterations in clinical parameters post COVID-19 infection.
Five clinical parameters of the two groups of patients, (A) HT group and (B) non-HT group was compared to identify alterations before and after COVID-19 infection within 90 days as clinical indices are not measured at every follow-up visit.
Abbreviations: PRE, prior to COVID-19 infection; Post, post COVID-19 infection; Hb, haemoglobin concentration; LDH, lactate dehydrogenase; LDL, low-density lipoprotein; lp(a), lipoprotein (a); 25-OH-D3, 25 hydroxyvitamin D3.
Discussion
The COVID-19 pandemic stands as a pivotal global public health crisis, distinguished by its rapid dissemination and unprecedented challenges in managing control measures, surpassing all previous epidemics of the past century [11]. COVID-19 has been found to impact several organs and systems, including the endocrine system [12,13], with potential short- and long-term consequences [14]. Notably, vaccination has emerged as a crucial strategy in combating the pandemic. According to the WHO’s COVID-19 weekly Epidemiological Update (Edition 83) [EB/OL], as of 26 November 2023, China’s vaccination rate has reached 90% [15].
Our findings indicate that patients with pre-existing hypothyroidism, whether due to HT, an inflammatory autoimmune disease, or other causes, undergo changes in thyroid function levels following COVID-19 infection. This aligns with the notion that the pituitary-thyroid axis should be regarded as a susceptible target of SARS-CoV-2, with direct or indirect pituitary injury described as a pivotal factor in potential thyroid hormone imbalance [16,17]. Notably, patients in the HT group exhibited a higher susceptibility to sore throat, cough, and fluctuations in thyroid hormone levels. Indicators displayed greater variability in the HT group compared to the non-HT group. Specifically, among HT patients, TSH levels decreased at 90 days post-COVID-19 infection compared to pre-infection levels. Furthermore, FT3 levels increased at 90 days post-infection, in contrast to levels observed at 30 days post-infection, and haemoglobin levels also showed an increase following infection. These observations were not evident in the non-HT group [18]. Our findings highlight variations in the risk and progression of SARS-CoV-2 infection among individuals with autoimmune and non-autoimmune thyroid dysfunction.
The immune response has been identified as a critical factor in COVID-19 symptoms and pathogenesis of COVID-19, with CD4+ and CD8+ T cells playing a pivotal role by targeting different SARS-CoV-2 proteins to combat the infection while aiding in the resolution phase of the disease [19]. In fact, SARS-CoV-2 infects cells by attaching its spike protein to the ACE2 receptor, thereby targeting and modulating the renin-angiotensin system (RAS), particularly the excessive activation of its classic detrimental axis (Ang II-AT1R) [20,21]. This axis is characterized by vasoconstriction, inflammation, oxidative stress, cellular proliferation, and various pro-apoptotic, pro-angiogenic, pro-thrombotic, pro-hypertrophic, and pro-fibrotic events [22]. RAS dysfunction can significantly trigger or exacerbate autoimmune diseases, with latent manifestations sometimes appearing months later [23]. Interestingly, ACE2 is located on the X chromosome, meaning women have two copies while men have one, which suggests differing regulatory mechanisms between genders [24]. Given the higher prevalence of HT in women, it is still unclear whether gender factors play a unique role in the course of illness for HT patients infected with COVID-19.
Our study also observed that vaccinated patients tend to exhibit more stable thyroid hormone levels, demonstrating vaccine stability. This finding is consistent with previous research that the inactivated SARS-CoV-2 vaccine does not interfere with the treatment of patients with Graves’ disease [25]. Additionally, research has demonstrated that vaccination may alleviate acute symptoms caused by SARS-CoV-2, such as abdominal pain, an abnormal sense of smell, dizziness, and breathing difficulties [26]. This alleviation may be attributed to the specific antibodies produced by coronavirus vaccines, which block the binding of SARS-CoV-2 to ACE2 receptors, thereby preventing viral invasion of host cells [27]. However, it is worth noting that vaccines can also cause thyroiditis and delayed-onset thyroid disorders [28,29]. Fajloun et al. suggest that vaccines may induce RAS dysfunction, leading to phenomena such as “antibody-dependent enhancement” (ADE) and “enhanced respiratory disease” (ERD), which increase the risk of reinfection [30,31]. Although the relationship between these phenomena and COVID-19 vaccines remains controversial, the antibody protection mechanism against any virus has the potential to amplify infection or trigger harmful immunopathology. Currently, there are no clinical findings, immunological tests, or biomarkers that can distinguish severe viral infections from immune-enhancing diseases [32,33].
Furthermore, our study found no significant differences in LDH, LDL, Lp(a), and 25-OH-D3 levels before and after COVID-19 infection. However, other research has shown contrasting results. A cohort study published in Lancet Diabetes & Endocrinology found a higher risk of dyslipidemia in the post-acute phase of COVID-19 infection (after 30 days), specifically with LDL levels exceeding 130 mg/dL [34]. In addition, LDH levels are known to be elevated in COVID-19 patients, particularly in severe cases, and gradually return to normal upon recovery [35]. Lp(a) levels, on the other hand, remain stable but tend to increase during the sustained pro-inflammatory state of COVID-19 [36]. Lastly, vitamin D deficiency has been linked to an increased risk of COVID-19 infection globally [37].
The COVID-19 pandemic is currently ongoing worldwide, with the virus undergoing continuous mutations [38]. Since the beginning of 2024, the KP.2 variant has spread in many countries, and its proportion among globally prevalent strains has gradually increased. In response to this evolving situation, it is recommended that the public continue to practice personal health precautions to minimize the risk of disease transmission. This necessitates determination and confidence in coexisting with the virus while remaining vigilant against new variants.
Our study has several limitations that should be noted. Firstly, the clinical and laboratory data were obtained from a single centre, which limits the generalizability of the findings to a unique experience. Furthermore, the inclusion and exclusion criteria applied in this study restricted the size of the patient cohort, thereby limiting the statistical power of the results. Additionally, the vaccines used in this study were all inactivated virus vaccines, and other types, such as adenoviral vector and nucleic acid vaccines, were not explored. Given the rapid mutation of SARS-CoV-2 and the global emergence of new variants, our results may not be fully applicable to other untested strains, necessitating further investigations with larger sample sizes and a broader range of vaccine types.
Despite these limitations, our study provides valuable insights into the infection patterns of COVID-19 among patients with pre-existing thyroid disorders. Considering the prevalence of hypothyroidism, a common endocrine disorder, any heightened risk associated with COVID-19 infection could have substantial public health implications. Therefore, our research holds unique clinical significance. Ongoing research is essential as the pandemic continues to evolve, for identifying factors that contribute to severe disease, enabling risk stratification, optimizing the reallocation of hospital resources, and guiding public health recommendations and interventions.
Conclusion
In summary, our study found that COVID-19 significantly affects thyroid function in Hashimoto’s hypothyroidism patients, causing thyroid hormone fluctuations within three months. Hemoglobin levels also changed pre- and post-infection. Inactivated virus vaccines helped stabilize the disease in this patient population.
Supplementary Material
Acknowledgements
We would like to thank all the patients for their support in this research, as well as the anonymous reviewers and the journal editor for their suggestions, which improved the overall quality of this manuscript.
Funding Statement
This research was supported by the National Natural Science Foundation of China (NO. 82370789) and the Innovation Program of Shanghai Municipal Science and Technology Commission-Yangtze Delta Regional Cooperation Project (NO. 22002400600).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
The study was designed by BXL and XYF. YHZ and YHH screened and organized data from the database. MYG and HYS collected and registered questionnaires. WQR and QZ analysed the data. TTS and LP conducted the visualization. BXL, QQ and TTF wrote the manuscript. FL, YDP, YFW and HBX revised and reviewed the article. All authors have read and approved the final manuscript.
Data availability statement
The data that support the findings of this study are openly available in figshare at doi.org/10.6084/m9.figshare.27979898.v1.
Ethics approval
All patients who have joined the TDC at Shanghai General Hospital have signed informed consent forms, agreeing to the use of their data for scientific research and analysis. All data is fully anonymized, ensuring no subject is identifiable in the study dataset. This study was approved by the Ethics Committee of Shanghai General Hospital, Jiao Tong University in Shanghai, China (2021SQ136). All methods in this study strictly adhered to the ethical standards outlined in the Declaration of Helsinki.
Supplemental data
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2441397
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data that support the findings of this study are openly available in figshare at doi.org/10.6084/m9.figshare.27979898.v1.