An intranasally administered adenovirus-vectored SARS-CoV-2 vaccine induces robust mucosal secretory IgA.

BACKGROUNDThe level of nasal spike-specific secretory IgA (sIgA) is inversely correlated with the risk of SARS-CoV-2 Omicron infection. This study aimed to evaluate the safety and immunogenicity of intranasal vaccination using Ad5-S-Omicron (NB2155), a replication-incompetent human type 5 adenovirus carrying Omicron BA.1 spike.METHODSAn open-label, single-center, investigator-initiated trial was carried out on 128 health care workers who had never been infected with SARS-CoV-2 and had previously received 2 or 3 injections of inactivated whole-virus vaccines, with the last dose given 3-19 months previously (median 387 days, IQR 333-404 days). Participants received 2 intranasal sprays of NB2155 at 28-day intervals between November 30 and December 30, 2022. Safety was evaluated by solicited adverse events and laboratory tests. The elevation of nasal mucosal spike-specific sIgA and serum neutralizing activities were assessed. All participants were monitored for infection by antigen tests, disease symptoms, and the elevation of nucleocapsid-specific sIgA in the nasal passage.RESULTSThe vaccine-related solicited adverse events were mild. Nasal spike-specific sIgA against 10 strains had a mean geometric mean fold increase of 4.5 after the first dose, but it increased much higher to 51.5 after the second dose. Serum neutralizing titers also increased modestly to 128.1 (95% CI 74.4-220.4) against authentic BA.1 and 76.9 (95% CI 45.4-130.2) against BA.5 at 14 days after the second dose. Due to the lifting of the zero-COVID policy in China on December 7, 2022, 57.3% of participants were infected with BA.5 between days 15 and 28 after the first dose, whereas no participants reported having any symptomatic infections between day 3 and day 90 after the second dose. The elevation of nasal nucleocapsid-specific sIgA on days 0, 14, 42, and 118 after the first dose was assessed to verify that these 2-dose participants had no asymptomatic infections.CONCLUSIONA 2-dose intranasal vaccination regimen using NB2155 was safe, was well tolerated, and could dramatically induce broad-spectrum spike-specific sIgA in the nasal passage. Preliminary data suggested that the intranasal vaccination may establish an effective mucosal immune barrier against infection and warranted further clinical studies.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR2300070346).FUNDINGNatural Science Foundation of China, Guangzhou Laboratory, The First Affiliated Hospital of Guangzhou Medical University.

A Pilot HRCT Follow-Up Study to Test the Feasibility of Predictive Efficacy of Serum Periostin in Idiopathic Pulmonary Fibrosis.

Background: While serum periostin and Krebs von den Lungen-6 (KL-6) have been acknowledged as independent markers in idiopathic pulmonary fibrosis (IPF) diagnosis, the clinical combinatory potential of these biomarkers combined with high-resolution computed tomography (HRCT) has yet to be fully explored. Methods: This retrospective study involved 78 participants, comprising 51 UIP-IPF patients and 27 healthy controls. All subjects underwent clinical and laboratory examinations, particularly the detection of periostin and KL-6 using ELISA with innovative HRCT fibrosis score evaluations at admission and discharge during hospitalization in UIP-IPF patients. Results: In our cohort of patients with IPF, predominantly male, over an average follow-up period of 195.27 days. Serum levels of periostin and KL-6 were significantly elevated in IPF patients compared to healthy controls (*p < 0.05). Post-treatment, KL-6 levels decreased significantly, while periostin levels increased. Notably, periostin exhibited superior prognostic accuracy over KL-6, with a higher AUC of 0.875 than 0.639 in ROC analysis. An increase in periostin levels correlated with disease progression, as evidenced by worsened HRCT fibrotic scores and decreased survival probability. These findings underscore periostin's potential as a reliable biomarker for assessing IPF severity and therapeutic response. Conclusion: Our findings underscore the preeminence of serum periostin over KL-6 in UIP-IPF diagnosis, particularly when conjoined with HRCT fibrosis score.

Novel prediction model of early screening lung adenocarcinoma with pulmonary fibrosis based on haematological index.

BACKGROUND: Lung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD. METHODS: We analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF. RESULTS: Males predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy. CONCLUSIONS: Our study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis.

Artificial intelligence reveals the predictions of hematological indexes in children with acute leukemia.

Childhood leukemia is a prevalent form of pediatric cancer, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the primary manifestations. Timely treatment has significantly enhanced survival rates for children with acute leukemia. This study aimed to develop an early and comprehensive predictor for hematologic malignancies in children by analyzing nutritional biomarkers, key leukemia indicators, and granulocytes in their blood. Using a machine learning algorithm and ten indices, the blood samples of 826 children with ALL and 255 children with AML were compared to a control group of 200 healthy children. The study revealed notable differences, including higher indicators in boys compared to girls and significant variations in most biochemical indicators between leukemia patients and healthy children. Employing a random forest model resulted in an area under the curve (AUC) of 0.950 for predicting leukemia subtypes and an AUC of 0.909 for forecasting AML. This research introduces an efficient diagnostic tool for early screening of childhood blood cancers and underscores the potential of artificial intelligence in modern healthcare.

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization.

Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment's heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

Long-term ambient ozone exposure and childhood asthma, rhinitis, eczema, and conjunctivitis: A multi-city study in China.

Evidence on the link of long-term exposure to ozone (O3) with childhood asthma, rhinitis, conjunctivitis and eczema is inconclusive. We did a population-based cross-sectional survey, including 177,888 children from 173 primary and middle schools in 14 Chinese cities. A satellite-based spatiotemporal model was employed to assess four-year average O3 exposure at both residential and school locations. Information on asthma, allergic rhinitis, eczema and conjunctivitis was collected by a standard questionnaire developed by the American Thoracic Society. We used generalized non-linear and linear mixed models to test the associations. We observed linear exposure-response associations between O3 and all outcomes. The odds ratios of doctor-diagnosed asthma, rhinitis, eczema, and conjunctivitis associated with per interquartile increment in home-school O3 concentration were 1.31 (95 % confidence interval [CI]: 1.28, 1.34), 1.25 (95 %CI: 1.23, 1.28), 1.19 (95 %CI: 1.16, 1.21), and 1.28 (95 %CI: 1.21, 1.34), respectively. Similar associations were observed for asthma-related outcomes including current asthma, wheeze, current wheeze, persistent phlegm, and persistent cough. Moreover, stronger associations were observed among children who were aged > 12 years, physically inactive, and exposed to higher temperature. In conclusion, long-term O3 exposure was associated with higher risks of asthma, allergic rhinitis, conjunctivitis and eczema in children.

Clinical biomarker profiles reveals gender differences and mortality factors in sepsis.

Background: Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males. Methods: This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison. Results: Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Gender-stratified comparisons identified male-specific (e.g. AFP, HDLC) and female-specific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality. Conclusion: These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Peripheral blood indicators and COVID-19: an observational and bidirectional Mendelian randomization study.

Blood is critical for health, supporting key functions like immunity and oxygen transport. While studies have found links between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we analyzed clinical data (n = 2,293, aged 18-65 years) from Guangzhou Medical University's first affiliated hospital (2022-present), identifying 34 significant indicators differentiating COVID-19 patients from healthy controls. Utilizing bidirectional Mendelian randomization analyses, integrating data from over 2.46 million participants from various large-scale studies, we established causal links for six blood indicators with COVID-19 risk, five of which is consistent with our observational findings. Specifically, elevated Troponin I and Platelet Distribution Width levels are linked with increased COVID-19 susceptibility, whereas higher Hematocrit, Hemoglobin, and Neutrophil counts confer a protective effect. Reverse MR analysis confirmed four blood biomarkers influenced by COVID-19, aligning with our observational data for three of them. Notably, COVID-19 exhibited a positive causal relationship with Troponin I (Tnl) and Serum Amyloid Protein A, while a negative association was observed with Plateletcrit. These findings may help identify high-risk individuals and provide further direction on the management of COVID-19.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

Decoding acute myocarditis in patients with COVID-19: Early detection through machine learning and hematological indices.

During the persistent COVID-19 pandemic, the swift progression of acute myocarditis has emerged as a profound concern due to its augmented mortality, underscoring the urgency of prompt diagnosis. This study analyzed blood samples from 5,230 COVID-19 individuals, identifying key blood and myocardial markers that illuminate the relationship between COVID-19 severity and myocarditis. A predictive model, applying Bayesian and random forest methodologies, was constructed for myocarditis' early identification, unveiling a balanced gender distribution in myocarditis cases contrary to a male predominance in COVID-19 occurrences. Particularly, older men exhibited heightened vulnerability to severe COVID-19 strains. The analysis revealed myocarditis was notably prevalent in younger demographics, and two subvariants COVID-19 progression paths were identified, characterized by symptom intensity and specific blood indicators. The enhanced myocardial marker model displayed remarkable diagnostic accuracy, advocating its valuable application in future myocarditis detection and treatment strategies amidst the COVID-19 crisis.

Association between Atopic Dermatitis and Colorectal Cancer: TET2 as a Shared Gene Signature and Prognostic Biomarker.

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

The genetic etiology of body fluids on chronic obstructive airways disease.

BACKGROUND: Numerous studies have documented significant alterations in the bodily fluids of Chronic Obstructive Pulmonary Disease (COPD) patients. However, existing literature lacks causal inference due to residual confounding and reverse causality. METHODS: Summary-level data for COPD were obtained from two national biobanks: the UK Biobank, comprising 1,605 cases and 461,328 controls, and FinnGen, with 6,915 cases and 186,723 controls. We also validated our findings using clinical data from 2,690 COPD patients and 3,357 healthy controls from the First Affiliated Hospital of Guangzhou Medical University. A total of 44 bodily fluid biomarkers were selected as candidate risk factors. Mendelian randomization (MR) and meta-analyses were used to evaluate the causal effects of these bodily fluids on COPD and lung function (FEV1/FVC). RESULTS: Mendelian randomization (MR) and meta-analyses, by integrating data from the UK Biobank and FinnGen cohort, found that 3 bodily fluids indicators (HDLC, EOS, and TP) were causally associated with the risk of COPD, two (EOS and TP) of which is consistent with our observational findings. Moreover, we noticed EOS and TP were causally associated with the risk of lung function (FEV1/FVC). CONCLUSIONS: The MR findings and clinical data highlight the independent and significant roles of EOS and TP in the development of COPD and lung function (FEV1/FVC), which might provide a deeper insight into COPD risk factors and supply potential preventative strategies.

Impact of ultra-low temperature storage on serum sIgE detection and allergic disease biobank feasibility.

Research has shown that the concentration and composition of biological samples may change after long-term ultra-low temperature storage. Consequently, this study examined the effect of ultra-low temperature storage on serum sIgE detection by comparing sIgE concentrations at various durations from the time of sample storage to subsequent testing. We selected 40 serum samples from the Guangzhou Medical University Affiliated First Hospital Biobank, which had been tested for house dust mites, dog hair, tobacco mold, cockroaches, and cow milk allergen sIgE. Samples were categorized by storage duration: 14 samples stored for 10 years, 12 for 5 years, and 14 for 3 years. They were also classified by sIgE positive levels: 15 samples at levels 1-2, 15 at levels 3-4, and 10 at levels 5-6. The allergen sIgE of these samples was retested using the same technology. Regardless of the type of allergen or the level of positivity, the majority of sIgE concentrations measured at the time of storage were higher than the current measurements, but the difference was not statistically significant. The correlation between the sIgE results at the time of storage and the current results was high for samples stored for 10 years (rs = 0.991, P < 0.001) and 5 years (rs = 0.964, P < 0.001). Serum allergen sIgE is stable when stored under ultra-low temperature conditions, making the construction of a biological sample bank for allergic diseases feasible. This will facilitate researchers in quickly obtaining samples, conducting technical research, and translating findings, thereby promoting the development of the field of allergy through integration of industry, academia, and research.

Utilizing Protein-Peptide Hybrid Microarray for Time-Resolved Diagnosis and Prognosis of COVID-19.

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.

ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after Cell Invasion.

Background: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.

The genetic associations of COVID-19 on genitourinary symptoms.

Background: Recently emerged reports indicated that patients with coronavirus disease 2019 (COVID-19) might experience novo genitourinary symptoms after discharge. Nevertheless, the causal associations and underlying mechanisms remain largely unclear. Methods: Genome-wide association study (GWAS) statistics for COVID-19 and 28 genitourinary symptoms with consistent definitions were collected from the COVID-19 Host Genetic Initiative, FinnGen, and UK Biobanks. Mendelian randomization (MR) analyses were applied to explore the causal effects of COVID-19 on genitourinary symptoms by selecting single-nucleotide polymorphisms as instrumental variables. Meta-analyses were conducted to evaluate the combined causal effect. Molecular pathways connecting COVID-19 and its associated disorders were evaluated by weighted gene co-expression network analysis (WGCNA) and enrichment analyses to extract insights into the potential mechanisms underlying the connection. Results: The MR and meta-analyses indicated that COVID-19 was causally associated with increased risk for calculus of the lower urinary tract (LUTC, OR: 1.2984 per doubling in odds of COVID-19, 95% CI: 1.0752-1.5680, p = 0.007) and sexual dysfunction (SD, OR: 1.0931, 95% CI: 1.0292-1.1610, p = 0.004). Intriguingly, COVID-19 might exert a slight causal protective effect on the progression of urinary tract infections (UTIs) and bladder cancer (BLCA). These results were robust to sensitivity analyses. Bioinformatic analyses indicated that the inflammatory-immune response module may mediate the links between COVID-19 and its associated disorders at the molecular level. Conclusions: In response to post-COVID-19 symptoms, we recommend that COVID-19 patients should strengthen the prevention of LUTC and the monitoring of sexual function. Meanwhile, the positive effects of COVID-19 on UTIs and BLCA should attach equal importance.

SARS-CoV-2 neutralising antibody therapies: Recent advances and future challenges.

The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.