Front. Med. Frontiers in Medicine Front. Med. 2296-858X Frontiers Media S.A. 10.3389/fmed.2025.1653394 Original Research Comparison of clinical features between Chlamydia psittaci and Legionella Chen Jiamei 1 † Writing – original draft Data curation Yang Libing 1 † Data curation Writing – review & editing Liu Yuni 2 Writing – original draft Data curation Zhou Jianliang 3 Validation Writing – review & editing Li Yongzhong 1 Writing – review & editing Supervision Wang Jin 1 * Writing – review & editing Validation Zheng Yixiang 4 Writing – review & editing Validation Department of Infectious Diseases, Hunan University of Medicine General Hospital, Huaihua, Hunan, China Department of Gastroenterology, Yiyang Third People’s Hospital, Yiyang, Hunan, China Department of Intensive Care Medicine, Hunan University of Medicine General Hospital, Huaihua, Hunan, China Department of Infectious Diseases, The First Affiliated Hospital of Xiangya Hospital, Changsha, Hunan, China Correspondence: Jin Wang, 13607410137@163.com

These authors share first authorship

 12 11 2025 2025 12 1653394 24 06 2025 20 10 2025 Copyright © 2025 Chen, Yang, Liu, Zhou, Li, Wang and Zheng. 2025 Chen, Yang, Liu, Zhou, Li, Wang and Zheng https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Objectives

Traditional diagnostic methods have difficulty distinguishing between Chlamydia psittaci (C. psittaci) pneumonia and Legionella pneumonia (L. pneumonia). This study aims to delineate the differences between C. psittaci pneumonia and L. pneumonia.

 Methods

This retrospective analysis included 71 cases of C. psittaci pneumonia and 21 cases of L. pneumonia, all confirmed via next-generation sequencing (NGS). We systematically collected and compared data on clinical characteristics, laboratory findings, chest CT imaging, bronchoscopic observations, and prognostic outcomes between the two groups.

 Results

In the C. psittaci pneumonia cohort, 64 patients (91.4%) had an opportunity to contact with poultry, with a maximum temperature of mean 39.6 °C. Additionally, 23 patients (32.4%) experienced dyspnea, and 57 patients (80.3%) exhibited relative bradycardia. Compared to patients with L. pneumonia, those with C. psittaci pneumonia had lower leukocyte counts, neutrophil counts, mononuclear cell counts, systemic inflammatory response index (SIRI), and urea levels, while lymphocyte-to-monocyte ratio (LMR), glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and creatine kinase (CK) levels were elevated. Next-generation sequencing (NGS) plays a crucial role in the early diagnosis of infectious pathogens. Multivariate analysis revealed differences in underlying diseases, residing in countryside, relative bradycardia, and LMR between the two groups.

 Conclusion

Several characteristics aid in differentiating C. psittaci pneumonia from L. pneumonia, including exposure to poultry, relative bradycardia, some infection indicators, ALT, AST, and CK. NGS addresses the limitations of traditional diagnostic methods. The early application of NGS facilitates the diagnosis of atypical pneumonia. Multivariate regression analysis suggested that underlying diseases, residing in countryside, relative bradycardia, and LMR is significant in differentiating C. psittaci pneumonia and L. pneumonia.

 Chlamydia psittaci pneumonia Legionella pneumonia clinical features next-generation sequencing diagnosis The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by the Hunan Provincial Natural Science Foundation Project (2023JJ50448), Huaihua Science and Technology Plan Project (2020R3331). section-at-acceptance Infectious Diseases: Pathogenesis and Therapy Introduction

Atypical bacterial pneumonia arises from infection with atypical pathogens that cannot be detected using Gram staining and are challenging to culture using standard methods. Common pathogens include Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, and Coxiella burnetii (Q fever) (1, 2). The predominant clinical manifestations encompass systemic and respiratory symptoms. Systemic symptoms, such as headache, low-grade fever, and general malaise, were more pronounced than respiratory symptoms, with the primary respiratory manifestation being a persistent dry cough. Chlamydia psittaci(C. psittaci) Chlamydia psittaci causes a rare form of pneumonia, comprising approximately 1% of community-acquired pneumonia cases, and is difficult to diagnose due to its nonspecific presentation (3, 4). The nonspecific nature of C. psittaci pneumonia’s clinical presentation, along with the limited accuracy of conventional diagnostic methods, makes diagnosis particularly challenging (5). Research indicates that Legionella spp. is among the four most common microbial causes of CAP-related hospitalizations (6). In patients with severe CAP requiring hospitalization, 2 to 15% are infected with Legionella (7, 8). The rarity and slow growth of Legionella in non-selective culture-based assays further complicate the diagnosis of such infections (9). The clinical manifestations and examination results of these two pathogens share many similarities. Common symptoms, which range from mild to severe and lack specificity, include fever, chills, cough, expectoration, dyspnea, fatigue, and some extrapulmonary manifestations (10). Research has demonstrated that infections caused by atypical pathogens, such as Legionella and Chlamydia psittaci, can affect multiple organ systems, complicating the differential diagnosis between L. pneumonia and C. psittaci pneumonia.

Next,-generation sequencing (NGS) has been extensively utilized due to its rapid and precise capabilities (11). Although various studies have individually reported on the clinical characteristics of C. psittaci pneumonia and Legionella pneumonia, there is a dearth of literature that directly compares them. This study aims to elucidate the clinical features, laboratory findings, and imaging results associated with C. psittaci pneumonia and L. pneumonia, offering clinicians essential insights for differentiating these conditions.

 Patients and methods Patient

A retrospective, single-center study was conducted at the Hunan University of Medicine General Hospital from March 2019 to January 2025. All included patients met the following criteria: (1) Diagnosis of atypical community-acquired pneumonia (CAP) in accordance with current clinical guidelines (12). Next-generation sequencing (NGS) diagnosis was performed using bronchoalveolar lavage fluid, lung tissue samples, blood specimens, or sputum samples. The exclusion criteria included patients with AIDS, tuberculosis, silicosis, active malignant tumors, and other severe underlying lung diseases.

 Study design

The clinical characteristics, laboratory examination results, and findings from chest computed tomography (CT) scans laboratory test results, bronchoscopic observations, and prognosis of each patient at the time of admission were systematically extracted from the hospital’s electronic medical record system. Specifically: (1) clinical characteristics included demographic information such as age and gender, residential area (urban vs. rural), underlying conditions (hypertension, coronary artery disease, diabetes mellitus, viral hepatitis, and immunosuppressive therapy), as well as clinical symptoms and signs. (2) laboratory tests comprised a comprehensive panel of blood tests, assessments of liver and kidney function, electrolyte levels, traditional inflammatory markers include C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6), while novel markers include the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and lymphocyte-to-white blood cell ratio (LWR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), plasma D-dimer concentrations, and myocardial enzyme levels. (3) the chest CT findings provided a detailed assessment of the extent of pulmonary involvement, including the presence of pleural or pericardial effusions, pleural thickening, and mediastinal lymphadenopathy. (4) Bronchoscopic observations revealed mucosal erythema, edema, and secretions.

 Next-generation sequencing detection method

Gene sequencing enables the direct acquisition of DNA from all microorganisms present in clinical samples, facilitating the study of microbial DNA composition and community function through genomics (13, 14). This technique is characterized by its rapidity, accuracy, and objectivity (11). It has been extensively applied in the diagnosis and treatment of infectious diseases, demonstrating significant advantages in identifying rare pathogens (15).

 Data analysis

Data analysis was conducted using SPSS software (version 26.0). Continuous variables with normal distribution are reported as means ± standard deviations, whereas those with non-normal distribution are presented as medians with interquartile ranges (IQR). Categorical variables are summarized using frequencies and percentages. For the purpose of statistical analysis, continuous data exhibiting a normal distribution were evaluated using the independent samples t-test, while non-normally distributed continuous data were analyzed via the Mann–Whitney U test. Categorical data were assessed using either the χ2 test or Fisher’s exact test, as deemed appropriate. All p-values reported are two-sided, with statistical significance defined at p < 0.05.

 Results Clinical characteristics

In this retrospective analysis, clinical data were systematically gathered from 92 patients diagnosed using Next-Generation Sequencing (NGS), which included 71 cases of C. psittaci pneumonia and 21 cases of L. pneumonia.

Within the C. psittaci pneumonia cohort, a majority of patients (91.4%) resided in rural areas, with many having neighbors who kept poultry. This proportion was significantly higher compared to the L. pneumonia group (47.6%). All patients with psittaci pneumonia presented with fever, and their maximum recorded temperatures were higher than those observed in patients with Legionella pneumonia. Furthermore, patients infected with C. psittaci demonstrated a significantly greater incidence of relative bradycardia compared to those with L. pneumophila (80.3% versus 23.8%, p = 0.000). furthermore, multivariate analysis revealed differences in Underlying diseases, Residing in countryside and Relative bradycardia between the Legionella pneumonia and Chlamydia psittaci. The General clinical data, clinical manifestations and Clinical signs are shown in Table 1.

General clinical data, clinical manifestations and clinical signs of patients with C. psittaci pneumonia and L. pneumonia.

Univariate analysis Multivariate analysis
Clinical features Chlamydia psittaci pneumonia (n = 71) Legionella pneumonia (n = 21) p value OR 95% CI p value
General clinical data
Gender (male/female) 46/25 16/5 0.328
Age (years) 62.410 ± 10.505 62.620 ± 13.673 0.94 1.011 0.965–1.059 0.650
Underlying diseases 35 (49.300%) 15 (71.400%) 0.074 0.286 0.092–0.896 0.032
Residing in countryside 64 (91.400%) 10 (47.600%) 0 0.028 0.002–0.368 0.007
Clinical manifestations
Maximum temperature 39.600 (39.000, 40.000) 39.000 (38.750, 39.600) 0.003 0.888 0.348–2.264 0.803
Cough 54 (76.100%) 18 (85.700%) 0.548
Coughing up phlegm 40 (56.300%) 16 (76.200%) 0.102
Chills 33 (46.500%) 6 (28.600%) 0.145
Anhelation 23 (32.400%) 14 (66.700%) 0.005 4.041 0.562–29.077 0.165
Clinical signs
Rough breathing sound 41 (57.700%) 12 (57.100%) 0.961
Low breathing sound 16 (22.500%) 4 (19.000%) 1
Wet rales 44 (62.000%) 12 (57.100%) 0.69
Relative bradycardia 57 (80.300%) 5 (23.800%) 0 0.053 0.005–0.579 0.016
Severe pneumonia 25 (35.200%) 7 (33.300%) 0.874
Laboratory parameters

Among patients with C. psittaci pneumonia, there were increased levels of the lymphocyte/monocyte ratio (LMR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK). Conversely, in the group with L. pneumophila pneumonia, patients exhibited higher levels of white blood cells (WBC), neutrophil count, monocyte count, and systemic inflammatory response index (SIRI), and. Furthermore, multivariate analysis revealed differences in LMR between the Legionella pneumonia and Chlamydia psittaci. The laboratory parameters are detailed in Table 2.

Laboratory parameters of patients with C. psittaci pneumonia and L. pneumonia.

Univariate analysis Multivariate analysis
Aboratory parameters (Unit) Chlamydia psittaci pneumonia (n = 71) Legionella pneumonia (n = 21) p value OR 95%CI p value
WBC (*109 /L) 8.170 ± 2.651 11.771 ± 6.234 0.017 2.268 0.334–15.383 0.402
Hb(g/l) 113.040 ± 21.080 110.760 ± 17.810 0.654
PLT (*109 /L) 145.000 (117.000,219.000) 131.000(92.500, 187.000) 0.418
N(%) 88.500 (83.400, 93.400) 88.400 (71.800, 94.450) 0.11
N (*109 /L) 7.312 ± 2.851 10.511 ± 6.144 0.047 0.420 0.062–2.865 0.376
M (*109 /L) 0.270 (0.160, 0.465) 0.496 ± 0.344 0.04 0.001 0.000–2.502 0.086
L (*109 /L) 0.485 (0.300, 0.738) 0.713 ± 0.515 0.353
NLR 13.330 (7.423, 26.115) 18.694 (7.978, 35.695) 0.21
LMR 1.852 (1.305,2.595) 1.187 (0.881,2.146) 0.035 0.459 0.233–0.903 0.024
LWR 0.067 (0.036, 0.109) 0.067 ± 0.058 0.221
PLR 343.791 (193.083, 467.659) 271.296 (167.040,418.867) 0.421
SII 2008.460 (982.488, 3980.680) 2262.028 (1090.996,6968.196) 0.692
SIRI 3.614 (2.170, 6.944) 9.473 ± 7.187 0.004 0.823 0.600–1.131 0.230
CRP(mg/l) 164.900 (121.520, 216.100) 162.112 ± 119.297 0.262
PCT(ug/l) 0.940 (0.400, 3.260) 0.910(0.285, 2.830) 0.46
ESR(mm/h) 74.740 ± 34.056 62.470 ± 30.847 0.19
IL-6(pg/ml) 95.360 (62.790, 342.100) 214.600 (57.765, 933.925) 0.222
D-dimer(μg/ml) 2.270 (1.230, 5.010) 1.810 (0.675, 4.880) 0.397
ALT(IU/L) 47.000 (24.000, 94.000) 21.000 (15.000, 40.500) 0.004 1.018 0.985–1.052 0.302
AST(IU/L) 77.000 (38.000, 141.000) 25.000 (14.500, 46.500) 0 1.006 0.976–1.038 0.685
ALB(g/L) 31.727 ± 6.120 31.790 ± 5.163 0.966
TBIL(umol/L) 12.600 (8.800, 20.300) 11.900 (6.850, 27.150) 0.612
DBIL(umol/L) 6.000 (4.000, 9.800) 5.900 (2.300, 12.650) 0.561
CREA-S(umol/L) 87.000 (72.000, 106.000) 94.000 (74.000, 174.000) 0.254
UA(umol/L) 196.000 (155.000, 270.500) 237.000 (161.000, 371.500) 0.176
LDH(U/L) 321.000 (255.000, 494.000) 310.480 ± 151.085 0.077
CK(U/L) 154.000 (82.000, 340.000) 72.000 (32.000, 136.500) 0.008 1.000 0.998–1.002 0.873
CK-MB(IU/L) 13.000 (8.000, 20.000) 15.810 ± 9.108 0.716
MYO(ug/L) 120.000 (69.000, 443.000) 109.000 (60.500, 336.000) 0.391
K (mmol/L) 3.769 ± 0.447 4.139 ± 1.055 0.132
Na (mmol/L) 136.326 ± 6.114 137.481 ± 4.931 0.431
Cl(mmol/L) 103.450 (99.900, 107.600) 103.324 ± 5.376 0.631
Ca (mmol/L) 1.970 (1.910, 2.060) 2.031 ± 0.169 0.07
Corrective Ca (mmol/L) 2.026 ± 0.145 2.077 ± 0.185 0.188

*WBC, white blood cell; PLT, platelets; N%, percentage of neutrophils; NLR: Neutrophil to lymphocyte ratio; MLR, monocyte/lymphocyte ratio; LMR, lymphocyte/monocyte ratio; LWR, lymphocyte/leukocyte ratio; PLR, platelet/ lymphocyte ratio; SII: platelet *Neutrophil/lymphocyte ratio; CRP, C-reactive protein; PCT, procalcitonin; ESR, erythrocyte sedimentation rate; IL-6, interleukin-6; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; DBIL, direct bilirubin; CREA-S, serum creatinine; UA, uric acid; LDH, lactate dehydrogenase; CK, creatine kinase; CK-MB, creatine kinase isoenzyme; MYO, myoglobin; ALB, albumin.

 Chest computed tomography and bronchoscopic observations

All patients underwent chest computed tomography (CT) examinations. Among those with C. psittaci pneumonia, 31 patients (43.7%) displayed unilateral lung lesions, whereas in the L. pneumophila pneumonia group, only 3 patients (14.3%) showed unilateral lung lesions. The chest CT findings are presented in Table 3.

Chest computed tomography and bronchoscopic observations of patients with C. psittaci pneumonia and L. pneumonia.

Inspection results Chlamydia psittaci pneumonia (n = 71) Legionella pneumonia (n = 21) p value
Chest computed tomography
Unilateral lesion 31 (43.700%) 3 (14.300%) 0.014
Irregular and inconsistent shadows 66 (94.300%) 19 (90.500%) 0.619
Pleural effusion 48 (67.600%) 15 (71.400%) 0.740
Pericardial effusion 20 (28.200%) 5 (23.800%) 0.693
Bronchial inflation sign 6 (8.500%) 1 (4.800%) 1.000
Pleural thickening 36 (50.700%) 9 (42.900%) 0.527
Mediastinal lymphadenopathy 31 (43.700%) 8 (38.100%) 0.650
Pulmonary nodular changes 8 (11.400%) 2 (9.500%) 1.000
Atelectasis 1 (2.900%) 1 (4.800%) 1.000
Bronchoscopic manifestations
Bronchial mucosa was obviously congested and swollen 64 (95.500%) 20 (100.000%) 1.000
Less secretion 42 (62.700%) 13 (65.000%) 0.851

Regarding bronchoscopic observations, 20 patients in the C. psittaci pneumonia group and 64 patients in the L. pneumophila pneumonia group underwent this procedure. The bronchoscopic findings are also included in Table 3.

 Treatment and recovery

Prior to diagnosis, the majority of patients received empirical treatment with a beta-lactam antibiotic, which was ultimately found to be ineffective. Subsequently, samples of bronchoalveolar lavage fluid (BALF), blood, lung tissue, or sputum were collected for next-generation sequencing (NGS) analysis to confirm the diagnosis and guide appropriate treatment changes. In the group with C. psittaci pneumonia, 51 patients (71.8%) received oxygen therapy; of these, 42 patients utilized a nasal cannula for oxygen inhalation, while 18 patients required ventilator-assisted breathing. Following treatment modifications, 65 patients (91.5%) exhibited gradual clinical and laboratory improvement. In the L. pneumophila pneumonia group, 20 patients (95.2%) received oxygen therapy; among them, 8 patients used a nasal cannula for oxygen inhalation, and 5 patients were treated with ventilator-assisted breathing. After treatment adjustments, 14 patients (66.7%) demonstrated gradual clinical and laboratory improvement.

 Discussion

In atypical pneumonia, both L. pneumophila and C. psittaci can affect multiple organ systems, and their clinical characteristics are largely the same (16, 17). Research has previously indicated that C. psittaci pneumonia is chiefly transmitted through the inhalation of aerosols containing dried secretions or waste from the respiratory systems of infected birds, also through bird bites, contact through the mouth, touching feathers and tissues of infected birds (18, 19). Legionella species are commonly found in various natural environments, including water sources and soil, comprising 58 species and 3 subspecies (20). Patients with L. pneumonia often have non-specific epidemiological histories, such as recent bathing, travel, or cruise ship exposure (16, 21). In the present study, both groups predominantly consisted of elderly male patients with pre-existing conditions. C. psittaci pneumonia was more frequently observed in rural areas, where individuals have increased exposure to poultry.

Previous research has demonstrated that common symptoms of C. psittaci pneumonia and L. pneumophila pneumonia include fever, cough, expectoration, dyspnea, and chills (22). The pneumonia caused by C. psittaci is known for respiratory and systemic symptoms, including muscle pain, headaches, and central nervous system involvement. Fever, dyspnea, dry cough, and headache are the most prevalent symptoms, common physical indicators are dry and wet rales in the lungs, paired with a relatively bradycardic pulse (23, 24). L. pneumophila pneumonia typically presents with a subacute onset, with over half of the patients experiencing fatigue, weakness, myalgia, chills, and high fever, often accompanied by a dry cough and chest pain. Some patients may also exhibit hemoptysis, nausea, vomiting, or abdominal diarrhea, and as lung lesions progress, severe cases may develop dyspnea (25). In this study, the majority of patients exhibited fever, cough, expectoration, rough breathing sounds, and wet rales. Patients with C. psittaci pneumonia demonstrated higher body temperatures, a greater incidence of dyspnea, and relative bradycardia. Multivariate analysis revealed most patients with Legionella pneumonia have underlying diseases, while those with Chlamydia psittaci pneumonia mostly residing in countryside and have a relative bradycardia.

Previous research has demonstrated that C. psittaci pneumonia may lead to normal or slightly elevated white blood cell counts (26), as well as increased levels of CRP and ESR in patients (27, 28). In contrast, leukocyte count and procalcitonin (PCT) levels are significantly elevated in cases of L. pneumophila pneumonia (29). New research has validated the effectiveness of inflammatory markers such as LMR, NLR, LWR, PLR, SIRI, and SII in accurately and sensitively reflecting the body’s inflammation levels, facilitating the evaluation of various diseases and their prognoses (30, 31). In the present study, the percentage of neutrophils, CRP, ESR, interleukin-6 (IL-6), and other inflammatory markers were significantly elevated in the majority of patients. Importantly, patients with C. psittaci pneumonia had lower levels of white blood cells, neutrophils, monocytes, SIRI, and urea than those with L. pneumophila pneumonia. Conversely, LMR, ALT, AST, and CK levels were higher in patients with C. psittaci pneumonia. Pulmonary imaging findings for C. psittaci pneumonia and L. pneumonia are similar, exhibiting diverse yet comparable features, including perihilar ground-glass opacities and unilateral or multilobar consolidation. In this study, C. psittaci pneumonia and L. pneumophila pneumonia were examined. Multivariate analysis showed that the LMR value of Chlamydia psittaci pneumonia was relatively higher.

Pulmonary imaging characteristics of C. psittaci pneumonia and L. pneumophila pneumonia exhibit similarities, with both conditions presenting varied findings such as perihilar ground-glass opacities and unilateral or multilobar consolidation (32, 33). In the present study, C. psittaci pneumonia and L. pneumophila pneumonia predominantly manifested as irregular and inconsistent shadows accompanied by pleural thickening.

The therapeutic agents deemed effective for C. psittaci pneumonia include tetracyclines, quinolones, and macrolides (34, 35). while L. pneumophila pneumonia is effectively treated with macrolides, rifampicin, and third-generation quinolones. C. psittaci pneumonia generally has a favorable prognosis, with a mortality rate as low as 1% when timely and appropriate treatment is administered, but this rate can increase to 10–20% in the absence of such treatment (36). In contrast, studies indicate that L. pneumophila pneumonia has a mortality rate of approximately 7% (37, 38). In this study, 65 patients (91.5%) with C. psittaci pneumonia achieved cure following treatment with doxycycline, whereas 14 patients (66.7%) with Legionella pneumonia were cured after receiving macrolide therapy.

This study presents several limitations. Firstly, the primary limitation is the inclusion of only 21 patients diagnosed with L. pneumophila pneumonia; a larger sample size would enhance the robustness of multivariate analyses. Secondly, the study was conducted as a single-sample retrospective analysis, and alternative diagnostic methods were not employed to confirm the diagnosis. Thirdly, urinary antigen testing for L. pneumophila pneumonia was not conducted.

 Conclusion

Although the clinical profile of patients suffering from C. psittaci pneumonia and L. pneumophila pneumonia are similar, inflammatory markers were elevated in patients with L. pneumophila pneumonia. Additionally, patients with C. psittaci pneumonia demonstrated better recovery outcomes compared to those with L. pneumophila pneumonia. The early application of next-generation sequencing (NGS) improved the detection rates of both C. psittaci pneumonia and L. pneumophila pneumonia, facilitated treatment guidance, and enhanced patient prognosis. Multivariate regression analysis suggested that underlying diseases, residing in countryside, relative bradycardia, and LMR is significant in differentiating C. psittaci pneumonia and L. pneumonia.

 Data availability statement

The original data of this article provided by the authors without inappropriate reservations.

 Author contributions

JC: Writing – original draft, Data curation. LY: Data curation, Writing – review & editing. YuL: Writing – original draft, Data curation. JZ: Validation, Writing – review & editing. YoL: Writing – review & editing, Supervision. JW: Writing – review & editing, Validation. YZ: Writing – review & editing, Validation.

 Acknowledgments

Our appreciation goes out to the patients and families involved in the study.

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

 Generative AI statement

The authors declare that no Gen AI was used in the creation of this manuscript.

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Edited by: Vivek P. Chavda, L.M. College of Pharmacy, India

Reviewed by: Hemant Khuntia, Siksha ‘O’ Anusandhan University, India

Nasima Ahmed, Dibrugarh University, India