An In Vitro Study of the Impact of IL-17A and IL-22 on Ciliogenesis in Nasal Polyps Epithelium via the Hippo-YAP Pathway.

BACKGROUND: Cilia loss and impaired motile ciliary functions are one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Interleukin-17A (IL-17A) and interleukin-22 (IL-22) are the canonical cytokines of type 3 inflammation, exhibiting similar functional effects on epithelial cells. In this study, we sought to examine the effects of IL-17A and IL-22 on ciliated cells and investigate the potential involvement of Hippo-Yes-associated protein (YAP) signaling in their influence on ciliogenesis. METHODS: We assessed both the mRNA and protein expression levels of IL-17A and IL-22 in nasal tissues obtained from patients with CRSwNP and compared them to those from healthy controls. To further explore the impact of IL-17A and IL-22, we established a primary human nasal epithelial cell (hNEC) model using different concentrations (2 ng/mL, 10 ng/mL, 50 ng/mL) for a duration of 28 days in an air-liquid interface (ALI) culture. Additionally, we employed the inhibitor verteporfin (VP) to investigate whether IL-17A andIL-22 exert their effects on ciliated cells via Hippo-YAP pathway. RESULTS: The mRNA and protein levels of IL-17A and IL-22 in CRSwNP were significantly higher than those in healthy controls, revealing a robust correlation between IL-17A and IL-22. YAP was highly expressed in the nucleus of ciliated cells in CRSwNP and displayed a positive correlation with clinical symptoms. Both IL-17A and IL-22 were found to reduce the number of ciliated cells. IL-17A, but not IL-22, suppressed ciliogenesis by disrupting the proper development and docking of the basal body of ciliated cells, resulting in motile ciliary dysfunctions. Furthermore, the expression of YAP within the nucleus of ciliated cells gradually declined as these cells reached the final stage of differentiation. However, this process was obstructed by IL-17A only. YAP inhibitors, such as Verteporfin, markedly reversed the effects of IL-17A by increasing the proportion of ciliated cells, suppressing nuclear YAP expression in these cells, and enhancing ciliary beating frequency. CONCLUSIONS: Both IL-17A and IL-22 are overexpressed in nasal epithelium of CRSwNP, which is associated with the impairment of epithelial cell differentiation. Furthermore, IL-17A has been shown to exert a disruptive effect on morphogenesis of motile cilia via activation of YAP.

Evaluating the consistency in different methods for measuring left atrium diameters.

BACKGROUND: The morphological information of the pulmonary vein (PV) and left atrium (LA) is of immense clinical importance for effective atrial fibrillation ablation. The aim of this study is to examine the consistency in different LA diameter measurement techniques. METHODS: Retrospective imaging data from 87 patients diagnosed with PV computed tomography angiography were included. The patients consisted of 50 males and 37 females, with an average age of (60.74 ± 8.70) years. Two physicians independently measured the anteroposterior diameter, long diameter, and transverse diameter of the LA using six different methods. Additionally, we recorded the post-processing time of the images. Physician 1 conducted measurements twice with a one-month interval between the measurements to assess intra-rater reliability. Using the intraclass correlation coefficient (ICC), the consistency of each LA diameter measurement by the two physicians was evaluated. We compared the differences in the LA diameter and the time consumed for measurements using different methods. This was done by employing the rank sum test of a randomized block design (Friedman M test) and the q test for pairwise comparisons among multiple relevant samples. RESULTS: (1) The consistency of the measured LA diameter by the two physicians was strong or very strong. (2) There were statistical differences in the anteroposterior diameter, long diameter, and transverse diameter of LA assessed using different methods (χ2 = 222.28, 32.74, 293.83, P < 0.001). (3) Different methods for measuring the diameters of LA required different amounts of time (χ2 = 333.10, P < 0.001). CONCLUSION: The results of left atrium (LA) diameter measurements conducted by different physicians were found to be reliable. However, the LA diameters obtained through various techniques exhibited variations. It was observed that measuring LA long diameters using only the VR (volume rendering) picture was the most clinically applicable method.

An Exploratory Pilot Study on the Application of Radiofrequency Ablation for Atrial Fibrillation Guided by Computed Tomography-Based 3D Printing Technology.

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation.

Advances in Image-Based Artificial Intelligence in Otorhinolaryngology-Head and Neck Surgery: A Systematic Review.

OBJECTIVE: To update the literature and provide a systematic review of image-based artificial intelligence (AI) applications in otolaryngology, highlight its advances, and propose future challenges. DATA SOURCES: Web of Science, Embase, PubMed, and Cochrane Library. REVIEW METHODS: Studies written in English, published between January 2020 and December 2022. Two independent authors screened the search results, extracted data, and assessed studies. RESULTS: Overall, 686 studies were identified. After screening titles and abstracts, 325 full-text studies were assessed for eligibility, and 78 studies were included in this systematic review. The studies originated from 16 countries. Among these countries, the top 3 were China (n = 29), Korea (n = 8), the United States, and Japan (n = 7 each). The most common area was otology (n = 35), followed by rhinology (n = 20), pharyngology (n = 18), and head and neck surgery (n = 5). Most applications of AI in otology, rhinology, pharyngology, and head and neck surgery mainly included chronic otitis media (n = 9), nasal polyps (n = 4), laryngeal cancer (n = 12), and head and neck squamous cell carcinoma (n = 3), respectively. The overall performance of AI in accuracy, the area under the curve, sensitivity, and specificity were 88.39 ± 9.78%, 91.91 ± 6.70%, 86.93 ± 11.59%, and 88.62 ± 14.03%, respectively. CONCLUSION: This state-of-the-art review aimed to highlight the increasing applications of image-based AI in otorhinolaryngology head and neck surgery. The following steps will entail multicentre collaboration to ensure data reliability, ongoing optimization of AI algorithms, and integration into real-world clinical practice. Future studies should consider 3-dimensional (3D)-based AI, such as 3D surgical AI.

Novel insights into central compartment atopic disease - a literature review.

INTRODUCTION: Central compartment atopic disease (CCAD) is a newly recognized variant subtype of chronic rhinosinusitis (CRS). Although CCAD has been reported to be correlated with allergy, there is still a considerable gap in our knowledge regarding CCAD. AREAS COVERED: We have conducted a thorough analysis of the literature on CCAD. This review provides current understanding and therapeutic strategies of CCAD. In this article, we will review the clinical presentations and parameters, allergy-related etiology, endotypes, and recommended management of CCAD. EXPERT OPINION: CCAD is considered as an aeroallergen-driven type 2/eosinophilic inflammatory pattern. Although CCAD can be diagnosed by endoscopy and radiology, as well as allergen test, pathogenesis and management strategies leave much to be desired, and further studies are needed.

Is it feasible to measure pulmonary vein data using volume rendering images?

BACKGROUND: Pulmonary vein (PV) data are commonly measured on multiplanar image reformation (MPR) images and volume rendering (VR) images. PURPOSE: To compared and analyze the advantages and disadvantages of PV data based on VR images and MPR images. MATERIAL AND METHODS: A total of 94 patients with atrial fibrillation (AF) with imaging data were included in the study. The respective image postprocessing time and the three surgical interventionists' preferences for the two images were recorded. A paired t-test or chi-square test was used to compare their difference, and P < 0.05 was considered statistically significant. RESULTS: There was no statistically significant difference between the data values including the maximal and minimal ostial diameters of the left superior PV (LSPV), the left inferior PV (LIPV), the right superior PV (RSPV), and the right inferior PV (RIPV) obtained by VR and MPR images (P > 0.05). Yet, the mean postprocessing time of VR images (15.10 ± 3.05 min) was shorter compared to MPR images (16.54 ± 2.60 min) (t = 22.84, P < 0.05). All three surgical interventionists preferred VR images (accounted for 85.1%, 86.2%, and 84.0%, respectively), and there was no statistical difference in the degree of image preference among the three (chi-square = 0.596, P = 0.963). CONCLUSION: PV data measurement could be performed on both VR and MRP images; however, the data on VR images were more intuitive and more accessible for interventional surgeons.

Predictive significance of Charcot-Leyden crystal structures for nasal polyp recurrence.

BACKGROUND: Charcot-Leyden crystals (CLCs) are recognized to be classic hallmarks of eosinophilic inflammation. Both protein and mRNA levels of CLC in nasal secretions and nasal brushing samples have been associated with nasal polyp recurrence. However, whether the crystalline CLC structures in nasal tissue could serve as an effective biomarker to predict polyp recurrence remains unclear. METHODS: A total of 110 patients with chronic rhinosinusitis with nasal polyps (CRSwNP) completing the postoperative follow-up over a period of 24 months were recruited. Hematoxylin and eosin staining was employed for CLCs identification. The predictive factors for polyp recurrence were determined by binary logistic regression analysis. RESULTS: Thirty three (30.00%) patients developed recurrence during a 24-month postoperative follow-up, in which 84.85% (28/33) patients had crystalline CLC structures. Logistic regression analysis showed that crystalline CLC structure in nasal tissues is predictive of polyp recurrence. Youden index demonstrated crystalline CLC structure higher than 1 per high power field can predict postoperative polyp recurrence with 84.80% sensitivity and 98.70% specificity. CONCLUSIONS: The crystalline CLC structures in nasal tissues may serve as an easy-counting and promising biomarker to predict CRSwNP recurrence.

Chinese Central Compartment Atopic Disease: The Clinical Characteristics and Cellular Endotypes Based on Whole-Slide Imaging.

Purpose: Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI). Methods: A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0. Results: CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP. Conclusion: Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.

Efficacy and Safety of Anti-Interleukin-5 Therapies in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The efficacy and safety of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved, and relevant meta-analyses are lacking. Additionally, mepolizumab has been evaluated in far fewer patients, and the evidence is unclear. We conducted a meta-analysis to identify evidence gaps that will guide future investigation of therapies targeting interleukin (IL)-5 signaling (anti-IL-5Rα or anti-IL-5) for CRSwNP. METHODS: We performed a systematic review and meta-analysis that were registered with PROSPERO (No. CRD42021276867). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on September 2, 2021. Only randomized controlled trials (RCTs) assessing anti-IL-5 treatments (anti-IL-5Rα or anti-IL-5) in adult patients for CRSwNP were included. RESULTS: Seven RCTs with 799 patients evaluating the efficacy and safety of treatments targeting IL-5 pathway (benralizumab [anti-IL-5Rα], mepolizumab, and reslizumab [anti-IL-5]) were included. The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better nasal polyp score (weighted mean difference [WMD]: -0.71; 95% confidence interval [CI]: [-0.87, -0.55]; p < 0.00001). Anti-IL-5 treatments were associated with a significantly better nasal congestion score (WMD: -1.73; 95% CI: [-2.29, -1.16]; p < 0.00001). Anti-IL-5 treatments were associated with a significantly better Sino-Nasal Outcome Test (SNOT-22) score (WMD: -11.30; 95% CI: [-14.77, -7.83]; p < 0.00001). The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better University of Pennsylvania Smell Identification Test (UPSIT) score (WMD: 2.09; 95% CI: [0.42, 3.77]; p = 0.01). Anti-IL-5 treatments significantly reduced the loss of smell score in the overall pooled meta-analysis (WMD: -1.38; 95% CI: [-1.97, -0.79]; p < 0.00001). In the overall pooled meta-analysis, anti-IL-5 treatments showed no difference with the placebo in the risk of adverse events (AEs; risk ratio [RR]: 1.01; 95% CI: [-0.93, 1.09]; p = 0.83) and serious AEs (SAEs; RR: 0.73; 95% CI: [0.40, 1.34]; p = 0.32). CONCLUSION: This systematic review and meta-analysis identified that anti-IL-5 treatments significantly improved the size of nasal polyps, health-related quality of life, and sense of smell in moderate to severe CRSwNP, and they were safe and well tolerated.

Which Is the Best Biologic for Nasal Polyps: Dupilumab, Omalizumab, or Mepolizumab? A Network Meta-Analysis.

INTRODUCTION: Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP. METHODS: We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included. RESULTS: Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746. CONCLUSION: This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.

Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP. DATA EXTRACTION AND SYNTHESIS: Two independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic. RESULTS: A total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=-1.20; 95% CI -1.48 to -0.92), Nasal Congestion Score (MD=-0.67; 95% CI -0.86 to -0.48), Sino-Nasal Outcome Test-22 (MD=-15.62; 95% CI -19.79 to -11.45), Total Nasal Symptom Score (MD=-1.84; 95% CI -2.43 to -1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61). CONCLUSIONS: This was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated. PROSPERO REGISTRATION NUMBER: CRD42020207639.

Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma.

BACKGROUND: Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. METHODS: We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP's role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP's role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. RESULTS: The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes. CONCLUSION: Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.

Artificial intelligence for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging.

BACKGROUND: artificial intelligence (AI) for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging (WSI) is lacking. We aim to establish an AI chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0) to obtain the proportion of inflammatory cells for cellular phenotyping diagnosis of nasal polyps and to explore the clinical significance of different phenotypes of nasal polyps on the WSI. METHODS: a total of 453 patients were enrolled in our study. For the development of AICEP 2.0, 179 patients (WSIs) were obtained from the Third Affiliated Hospital of Sun Yat-Sen University (3HSYSU) from January 2008 to December 2018. A total of 24,625 patches were automatically extracted from the regions of interest under a 400× HPF by Openslide and the number of inflammatory cells in these patches was counted by two pathologists. For the application of AICEP 2.0 in a prospective cohort, 158 patients aged 14-70 years old with chronic rhinosinusitis with nasal polyps (CRSwNP) who had undergone endoscopic sinus surgery at 3HSYSU from June 2020 to December 2020 were included for preoperative demographic characteristics. For the application of AICEP 2.0 in a retrospective cohort, 116 patients with CRSwNP who had undergone endoscopic sinus surgery from May 2016 to June 2017 were enrolled for the recurrence rate. The proportion of inflammatory cells of these patients on WSI was calculated by our AICEP 2.0. FINDINGS: for AICEP 2.0, the mean absolute errors of the ratios of eosinophils, lymphocytes, neutrophils, and plasma cells were 1.64%, 2.13%, 1.06%, and 1.22%, respectively. The four phenotypes of nasal polyps were significantly different in clinical characteristics (including asthma, itching, sneezing, total IgE, peripheral eosinophils%, tissue eosinophils%, tissue neutrophils%, tissue lymphocytes%, tissue plasma cells%, and recurrence rate; P <0.05), but there were no significant differences in age distribution, onset time, total VAS score, Lund-Kennedy score, or Lund-Mackay score. The percentage of peripheral eosinophils was positively correlated with the percentage of tissue eosinophils (r = 0.560, P <0.001) and negatively correlated with tissue lymphocytes% (r = -0.489, P <0.001), tissue neutrophils% (r = -0.225, P = 0.005), and tissue plasma cells% (r = -0.266, P = 0.001) in WSIs.

Using the internet search data to investigate symptom characteristics of COVID-19: A big data study.

OBJECTIVE: Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19) to improve control and prevention. METHODS: Using the Baidu Index Platform (http://index.baidu.com) and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume (SV) of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020 and the epidemic data in Hubei province and the other top 9 impacted provinces in China. Data of 2020 were compared with those of the previous three years. Data of Hubei province were compared with those of the other 9 provinces. The differences and characteristics of the SV of COVID-19-related symptoms, and the correlations between the SV of COVID-19 and the number of newly confirmed/suspected cases were analyzed. The lag effects were discussed. RESULTS: Comparing the SV from January 1, 2020 to February 20, 2020 with those for the same period of the previous three years, Hubei's SV for cough, fever, diarrhea, chest tightness, dyspnea, and other symptoms were significantly increased. The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms (P＜0.001). The SV of COVID-19 in Hubei province was significantly correlated with the number of newly confirmed/suspected cases (r confirmed = 0.723, r suspected = 0.863, both p < 0.001). The results of the distributed lag model suggested that the patients who searched relevant symptoms on the Internet may begin to see doctors in 2-3 days later and be confirmed in 3-4 days later. CONCLUSION: The total SV of lower respiratory symptoms was higher than that of upper respiratory symptoms, and the SV of diarrhea also increased significantly. It warned us to pay attention to not only the symptoms of the lower respiratory tract but also the gastrointestinal symptoms, especially diarrhea in patients with COVID-19. Internet search behavior had a positive correlation with the number of newly confirmed/suspected cases, suggesting that big data has an important role in the early warning of infectious diseases.