BACKGROUND:Previous research indicated that physicians possess limited knowledge of the diagnosis and treatment of invasive fungal disease (IFD). OBJECTIVE:This study aimed to assess the efficacy of training via video or PDF formats in increasing physicians' knowledge of IFD. METHODS:This was a multicentre, cluster-randomised controlled trial involving 18 tertiary hospitals in China. Physicians specialising in IFD clinical diagnosis and treatment from four departments were randomised 1:1 into a video training group or PDF training group, and questionnaires were completed before and after training. The primary outcome was the change in total questionnaire score before and after training. RESULTS:Of the 294 participants, 146 were assigned to the video group and 148 to the PDF group. Engagement with the training materials was observed among 127 participants from the video group and 135 from the PDF group. In the per-protocol set (PPS), post-training score improvements for total scores (p = 0.008), invasive candidiasis scores (p < 0.001), and invasive aspergillosis scores (p = 0.044) in the video group were significantly greater than those in the PDF group. Overall, 161 (61.5%) physicians in the PPS exhibited enhanced total scores post-training, with the video group outperforming the PDF group (70.9% vs. 52.6%, p = 0.002). The findings in the FAS were largely consistent with those observed in the PPS. CONCLUSION:Both video and PDF training modules are appealing to physicians. Further, the video training module displayed superior efficacy in improving physicians' knowledge of IFD.

Objective To visualize and quantify regional pulmonary aerosol deposition and early airway clearance using aerosolized [ 18 F]NaF PET/CT in bronchiectasis. Methods In this prospective study, 77 adults with CT-confirmed bronchiectasis underwent aerosolized [ 18 F]NaF PET/CT. Regional deposition in bronchiectatic versus healthy lung was assessed on the 0-min scan using target-to-blood ratio (TBR) and total deposited activity. Deposition robustness was evaluated across different nebulizer types. A subgroup underwent dynamic imaging (0–30 min) followed by serial static scans up to 120 min, with kinetic analysis using a dual-pathway clearance model. Results The 0-min PET/CT demonstrated visually apparent photopenic defects in bronchiectatic regions. Quantitatively, bronchiectatic lung showed significantly lower deposition than healthy lung (TBR: 1.30 [0.63–1.58] vs. 2.30 [1.60–2.65]; p < 0.05) and markedly reduced total activity (43.18 [5.7–47.08] vs. 1413.33 [581.95–2155.68]; p < 0.0001). These findings were consistent across all nebulizer systems. Dynamic imaging showed early clearance was dominated by mucociliary transport (kmc > kabs), with minimal systemic absorption. Serial imaging (0–120 min) showed no increase in bronchiectatic activity, while healthy lung activity declined gradually, indicating 0 min as the optimal time point for deposition assessment. Bronchodilator administration did not alter clearance kinetics in bronchiectatic regions. Conclusion Aerosolized [ 18 F]NaF PET/CT enables quantitative assessment of regional aerosol deposition and airway clearance in bronchiectasis, revealing persistent deposition deficits in diseased airways and mucociliary-dominant early clearance with minimal systemic absorption.

Medical AI agents represent a transformative paradigm in healthcare, distinguished from traditional AI by their autonomy, adaptability, and ability to manage complex tasks. This review introduces a conceptual framework for these agents built on four core components: planning, action, reflection, and memory. We examine the framework's application across key clinical domains, from enhancing diagnostic accuracy and personalizing treatment to guiding robotic surgery and enabling real-time patient monitoring. The review critically analyzes implementation challenges, including technical integration, clinician adoption, regulatory adaptation, and ethical considerations like data privacy and algorithmic bias. Future directions are explored, including the shift toward proactive, multi-agent collaborative systems and the visionary AI Agent Hospital concept. While these agents hold immense potential to revolutionize healthcare delivery by improving efficiency and patient outcomes, their successful and equitable integration hinges on navigating these profound technical, ethical, and regulatory hurdles.

Background:Elevated serum Aspergillus-specific immunoglobulin G (IgG) is a key diagnostic criterion for chronic pulmonary aspergillosis (CPA). This study evaluated the diagnostic performance of Aspergillus-specific IgG testing, comparing rapid immunochromatographic point-of-care test (ICT-POCT) with enzyme-linked immunosorbent assay (ELISA) for CPA and its subtypes, while identifying factors influencing test accuracy. Methods:We recruited 112 CPA patients and 61 non-CPA controls with pulmonary diseases from The First Affiliated Hospital of Guangzhou Medical University between December 2021 and November 2022. CPA diagnosis followed composite clinical, radiological, and microbiological criteria. Serum Aspergillus-specific antibodies were analyzed using quantitative ELISA (IgG) and ICT [IgG/immunoglobulin M (IgM)]. Bronchoalveolar lavage (BAL) Aspergillus galactomannan (GM) was tested where available. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results:90% of CPA patients had elevated Aspergillus-specific IgG antibodies by ImmunoCAP. ICT assay demonstrated superior overall diagnostic performance (sensitivity: 88.4%; specificity: 95.1%) vs. ELISA [58.9% sensitivity, 82.0% specificity at 80 arbitrary units per milliliter (AU/mL) cut-off]. Combined testing achieved peak specificity (98.4%) but reduced sensitivity vs. individual tests. Among patients with a history of antifungal treatment, the sensitivity of ICT assay varied by subtypes: 78.6% for chronic cavitary pulmonary aspergillosis (CCPA), 57.1% for chronic fibrosing pulmonary aspergillosis (CFPA), 66.7% for simple aspergilloma (SA), 66.7% for subacute invasive aspergillosis (SAIA), and 50% for Aspergillus nodule(s) (AN). In addition, the sensitivity of the ICT assay differed in comorbidities: 76.5% in patients with chronic obstructive pulmonary disease (COPD), 97.3% in patients with bronchiectasis, and 96.7% in patients with cavitary pulmonary tuberculosis. Notably, prior antifungal and steroid therapy decreased the performance of both assays. Conclusions:The Aspergillus-specific IgG ICT assay shows significant diagnostic value for CPA, particularly in untreated patients and CCPA subtype. Its high specificity and rapid format position it as a valuable point-of-care tool for prompt CPA diagnosis in resource-limited settings.

Aging is the gradual decline in physiological function essential for survival and reproduction. Unlike age-associated diseases, aging affects all individuals within a species, causing progressive impairments across multiple systems. Research shows that altering specific genes or dietary factors can extend lifespan, implicating molecular pathways in controlling senescence. Chronological age (CA) is a common measure of aging, but other hallmarks like telomere shortening better quantify functional decline. Identifying age-related hallmarks can help manipulate aging, spurring interest in aging clocks. These clocks predict biological age (BA) more precisely than CA, reflecting actual physiological health. As global life expectancy continues to rise, aging clocks hold promise for developing therapies to extend healthspan and improve life quality during aging.

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Background:Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods:Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results:Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions:This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Background Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. Methods We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. Results We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. Conclusion We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Research on virus/receptor interactions has uncovered various mechanisms of antibody-mediated neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, understanding of neutralization by antibodies targeting the silent face, which recognize epitopes on glycan shields, remains limited, and their potential protective efficacy in vivo is not well understood. This study describes a silent face neutralizing antibody, 3711, which targets a non-supersite on the N-terminal domain (NTD) of the spike protein. Cryo-EM structure determination of the 3711 Fab in the spike complex reveals a novel neutralizing epitope shielded by glycans on the spike's silent face. Antibody 3711 inhibits the interaction between the receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (hACE2) through steric hindrance and exhibits superior in vivo protective effects compared to other reported NTD-targeted monoclonal antibodies (mAbs). Competition assays and antibody repertoire analysis indicate the rarity of antibodies targeting the 3711-related epitope in SARS-CoV-2 convalescents, suggesting the infrequency of NTD silent face-targeted neutralizing antibodies during SARS-CoV-2 infection. As the first NTD silent face-targeted neutralizing antibody against SARS-CoV-2, the identification of mAb 3711, with its novel neutralizing mechanism, enhances our understanding of neutralizing epitopes on glycan shields and elucidates epitope-guided viral mutations that evade specific antibodies.

The role of fibroblast activation protein (FAP)-targeted imaging in systemic vasculitis is currently unclear. We aimed to evaluate the clinical value of fluorine-18-labeled FAP inhibitor 42 ([18F]FAPI-42) in patients with systemic vasculitis and to compare with [18F]fluorodeoxyglucose (FDG) imaging. Patients with systemic vasculitis who underwent dual-tracer PET/CT([18F]FDG and [18F]FAPI) imaging from September 2020 to March 2022 were retrospectively analyzed. Positive lesions are defined as vascular/extravascular lesions with increased tracer uptake above surrounding background, which cannot be attributed to the physiologic biodistribution of the radiotracer. The vascular/extravascular lesion detection rate and semiquantitative values (SUVmax, TBRblood and TBRliver) of [18F]FAPI and [18F]FDG were compared, and the correlation between the extent and range of tracer uptake and levels of inflammatory markers was investigated. Thirty patients (13 males and 17 females; mean age, 52.5 ± 17.2 years) with systemic vasculitis were included (17 large vessel vasculitis, 10 anti-neutrophil cytoplasmic antibody-associated vasculitis, 2 Behcet’s disease and 1 polyarteritis nodosa). [18F]FDG PET/CT had positive findings in 93.3

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible but causes less severe disease compared to other variants. However, its association with sepsis incidence and outcomes is unclear. This study aimed to investigate the incidence of Omicronassociated sepsis, as per the Sepsis 3.0 definition, in hospitalized patients, and to explore its relationship with clinical characteristics and prognosis. Methods: This multicenter retrospective study included adults hospitalized with confirmed SARS-CoV-2 infection across six tertiary hospitals in Guangzhou, China from November 2022 to January 2023. The Sequential Organ Failure Assessment (SOFA) score and its components were calculated at hospital admission to identify sepsis. Outcomes assessed were need for intensive care unit (ICU) transfer and mortality. Receiver operating characteristic curves evaluated the predictive value of sepsis versus other biomarkers for outcomes. Results: A total of 299 patients (mean age: 70.1 +/- 14.4 years, 42.14% female) with SOFA score were enrolled. Among them, 152 were categorized as non -serious cases while the others were assigned as the serious group. The proportion of male patients, unvaccinated patients, patients with comorbidity such as diabetes, chronic cardiovascular disease, and chronic lung disease was significantly higher in the serious than non -serious group. The median SOFA score of all enrolled patients was 1 (interquartile range, 0-18). In our study, 147 patients (64.19% ) were identified as having sepsis upon hospital admission, with the majority of these septic patients (113, representing 76.87%) being in the serious group, the respiratory, coagulation, cardiovascular, central nervous, and renal organ SOFA scores were all significantly higher in the serious compared to the non -serious group. Among septic patients, 20 out of 49 (40.81%) had septic shock as indicated by lactate measurement within 24 hours of admission, and the majority of septic patients were in the serious group (17/20, 76.87%). Sepsis was present in 118 out of 269 (43.9%) patients in the general ward, and among those with sepsis, 34 out of 118 (28.8%) later required ICU care during hospitalization. By contrast, none of the patients without sepsis required ICU care. Moreover, the mortality rate was significantly higher in patients with than without sepsis. Conclusions: A considerable proportion of patients infected with Omicron present with sepsis upon hospital admission, which is associated with a poorer prognosis. Therefore, early recognition of viral sepsis by evaluation of the SOFA score in hospitalized coronavirus disease 2019 patients is crucial.

Omicron, as the emerging variant with enhanced vaccine tolerance, has sharply disrupted most therapeutic antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the subgenus Sarbecovirus, members of which share high sequence similarity. Herein, we report one sarbecovirus antibody, 5817, which has broad-spectrum neutralization capacity against SARS-CoV-2 variants of concern (VOCs) and SARS-CoV, as well as related bat and pangolin viruses. 5817 can hardly compete with six classes of receptor-binding-domain-targeted antibodies grouped by structural classifications. No obvious impairment in the potency is detected against SARS-CoV-2 Omicron and subvariants. The cryoelectron microscopy (cryo-EM) structure of neutralizing antibody 5817 in complex with Omicron spike reveals a highly conserved epitope, only existing at the receptor-binding domain (RBD) open state. Prophylactic and therapeutic administration of 5817 potently protects mice from SARS-CoV-2 Beta, Delta, Omicron, and SARS-CoV infection. This study reveals a highly conserved cryptic epitope targeted by a broad sarbecovirus neutralizing antibody, which would be beneficial to meet the potential threat of pre-emergent SARS-CoV-2 VOCs.

Background The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW + ) or absence (TW − ) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW + and TW − groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW + group than in the TW − group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW − group. At 5 years, 53.1% of patients in the TW + group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW − group (p<0.05). 34 patients in the TW + group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW + bronchioles on CT predicted progression of bronchiectasis. Conclusion Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.

Host-pathogen interactions and pathogen evolution are underpinned by protein-protein interactions between viral and host proteins. An understanding of how viral variants affect protein-protein binding is important for predicting viral-host interactions, such as the emergence of new pathogenic SARS-CoV-2 variants. Here we propose an artificial intelligence-based framework called UniBind, in which proteins are represented as a graph at the residue and atom levels. UniBind integrates protein three-dimensional structure and binding affinity and is capable of multi-task learning for heterogeneous biological data integration. In systematic tests on benchmark datasets and further experimental validation, UniBind effectively and scalably predicted the effects of SARS-CoV-2 spike protein variants on their binding affinities to the human ACE2 receptor, as well as to SARS-CoV-2 neutralizing monoclonal antibodies. Furthermore, in a cross-species analysis, UniBind could be applied to predict host susceptibility to SARS-CoV-2 variants and to predict future viral variant evolutionary trends. This in silico approach has the potential to serve as an early warning system for problematic emerging SARS-CoV-2 variants, as well as to facilitate research on protein-protein interactions in general.

To combat SARS-CoV-2 variants and MERS-CoV, as well as the potential re-emergence of SARS-CoV and spillovers of sarbecoviruses, which pose a significant threat to global public health, vaccines that can confer broad-spectrum protection against betacoronaviruses (β-CoVs) are urgently needed. A mosaic ferritin nanoparticle vaccine is developed that co-displays the spike receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 Wild-type (WT) strain and evaluated its immunogenicity and protective efficacy in mice and nonhuman primates. A low dose of 10 µg administered at a 21-day interval induced a Th1-biased immune response in mice and elicited robust cross-reactive neutralizing antibody responses against a variety of β-CoVs, including a series of SARS-CoV-2 variants. It is also able to effectively protect against challenges of SARS-CoV, MERS-CoV, and SARS-CoV-2 variants in not only young mice but also the more vulnerable mice through induction of long-lived immunity. Together, these results suggest that this mosaic 3-RBD nanoparticle has the potential to be developed as a pan-β-CoV vaccine.

The high risk of postoperative mortality in lung adenocarcinoma (LUAD) patients is principally driven by cancer recurrence and low response rates to adjuvant treatment. Here, A combined cohort containing 1,026 stage I-III patients was divided into the learning (n = 678) and validation datasets (n = 348). The former was used to establish a 16-mRNA risk signature for recurrence prediction with multiple statistical algorithms, which was verified in the valida- tion set. Univariate and multivariate analyses confirmed it as an independent indicator for both recurrence-free survival (RFS) and overall survival (OS). Distinct molecular characteristics between the two groups including genomic alterations, and hallmark pathways were compre- hensively analyzed. Remarkably, the classifier was tightly linked to immune infiltrations, high- lighting the critical role of immune surveillance in prolonging survival for LUAD. Moreover, the classifier was a valuable predictor for therapeutic responses in patients, and the low-risk group was more likely to yield clinical benefits from immunotherapy. A transcription factor regulato- ry protein-protein interaction network (TF-PPI-network) was constructed via weighted gene co-expression network analysis (WGCNA) concerning the hub genes of the signature. The con- structed multidimensional nomogram dramatically increased the predictive accuracy. There- fore, our signature provides a forceful basis for individualized LUAD management with promising potential implications. 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

BACKGROUND:Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. OBJECTIVES:To evaluate physicians' perspectives on the diagnosis and management of IFD. METHODS:Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. RESULTS:The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the β-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. CONCLUSION:This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.

BACKGROUND:Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain.METHODS:We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared.RESULTS:The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation.CONCLUSIONS:A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.