OBJECTIVES: COVID-19 impacts physical and respiratory health, and the clinical presentation ranges from asymptomatic cases to severe infections requiring hospitalisation. While the long-term effects on lung function and...OBJECTIVES: COVID-19 impacts physical and respiratory health, and the clinical presentation ranges from asymptomatic cases to severe infections requiring hospitalisation. While the long-term effects on lung function and physical capacity are well-documented in moderate to severe cases, the long-term outcome for individuals with mild COVID-19 remains poorly understood. This study investigates the long-term recovery of physical capacity and breathlessness among both hospitalised and non-hospitalised individuals. METHODS: This prospective cohort study enrolled individuals with confirmed SARS-CoV-2 infection between April 2020 and May 2021 through the CoVUm-study. Participants underwent assessments of lung function at 3-6 months after infection and attended follow-ups up to three years post-infection. Physical capacity was evaluated at follow-ups, using the one-minute sit-to-stand test and the modified Medical Research Council scale to assess breathlessness. RESULTS: The cohort included 291 participants, 35% of whom were hospitalised during SARS-CoV-2 infection. At the 3-year follow-up, 191 participants completed the physical capacity test and 179 had an assessment of breathlessness. Physical capacity improved significantly in the total cohort up to two years post-infection, where improvement plateaued. Hospitalisation and impaired diffusing capacity were significantly associated with reduced physical capacity (beta -6.4, p < 0.001; beta -8.9, p < 0.001, respectively) and breathlessness (beta 3.9, p < 0.001; beta 1.6, p = 0.012, respectively). While non-hospitalised participants demonstrated improvements in physical capacity for up to two years, improvement for hospitalised individuals plateaued by six months. CONCLUSION: Hospitalisation and impaired diffusing capacity are strong independent predictors of reduced physical capacity and persistent breathlessness up to three years post-infection. Non-hospitalised individuals also experience long-term reductions in physical capacity, underscoring the need for targeted rehabilitation strategies.
Mueller M, Blandino A, Scherer D
… +15 more, Zulantay I, Apt W, Varela NM, Llancaqueo M, Garcia L, Ortiz L, Nicastri E, Giancola ML, Angheben A, Gabrielli S, Rounge TB, Langseth H, Waldenberger M, Salinas-Alvarez P, Lorenzo Bermejo J
BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6-7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chroni...BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects around 6-7 million people in Latin America and hundreds of thousands in the United States and Europe. A main complication of chronic Chagas disease is cardiomyopathy, possibly manifesting as arrhythmias, heart failure, or sudden cardiac death. Understanding the link between T. cruzi infection and cardiomyopathy is essential for early diagnosis and adequate treatment. METHODS: We sequenced small RNAs in serum samples from 228 Chagas patients recruited in Chile, Bolivia and Italy. After bioinformatic processing of sequencing data to quantify serum miRNA expression, robust logistic regression was applied to identify miRNAs differentially expressed in Chagas patients with abnormalities in electrocardiography (ECG), bundle-branch block on ECG, and high Kuschnir scores. We also investigated the association between genotype-based miRNA expression and the risk of abnormal ECG findings. FINDINGS: As reported, the risk of abnormal ECG findings was higher in male patients and increased with age. Three miRNAs showed lower serum expression levels in patients with abnormal ECG: miRNA-101-3p, miRNA-576-3p and miRNA-629-5p (p < 0.0002), especially in patients with high Kuschnir scores. The expression of miRNA-629-5p was negatively correlated with the CCL5 expression (p = 3.7×10), a chemokine frequently reported in Chagas disease. Gene enrichment analyses indicated involvement of cytokine signalling in Chagas cardiomyopathy. INTERPRETATION: The findings demonstrate the potential of circulating miRNAs as diagnostic biomarkers for Chagas cardiomyopathy. The associations found with disease severity and immune response may help to improve our knowledge of complications' development in Chagas disease.
OBJECTIVES: The aim of this work was to study the epidemiology of urogenital trichomoniasis in the setting of systematic screening of STIs, using a multiplex molecular assay. Besides, the specificity for T. vaginalis det...OBJECTIVES: The aim of this work was to study the epidemiology of urogenital trichomoniasis in the setting of systematic screening of STIs, using a multiplex molecular assay. Besides, the specificity for T. vaginalis detection of the syndromic panel was assessed comparatively to an in-house PCR. METHODS: 41,507 samples sent for STI screening between 2020 and 2024 were analysed using the Allplex® STI Essential molecular panel targeting T. vaginalis, C. trachomatis, N. gonorrhoeae, M. genitalium, M. hominis, Ureaplasma parvum, and U. urealyticum. Remaining samples positive for T. vaginalis were stored for confirmation using a simplex in-house qPCR assay targeting the beta-tubulin gene. RESULTS: 337 (0.8%) samples (282 patients; 0.93%) were positive for T. vaginalis. The highest rate of positivity was observed in patients aged between 20 and 24 (1.6%), whereas the number of cases over 45 years was anecdotal (0.4%). Prevalence was ten times lower in men than in women. Twenty-four percent were co-infected with at least one pathogen, i.e., C. trachomatis (n=17%) and/or M. genitalium (9.2%) and/or N. gonorrhoeae (3.6%). More than half patients positive for T. vaginalis were asymptomatic, of whom 88% were treated. Symptomatic patients presented mostly with abnormal leucorrhea, pruritus and/or dysuria. Amplification of 160 samples by simplex PCRs showed an excellent concordance rate of 95% (n= 152/160) with the multiplex PCR. CONCLUSIONS: Allplex® STI Essential multiplex PCR assay improves the detection of T. vaginalis with an excellent specificity and therefore represents an interesting tool to evaluate the prevalence of this neglected infection.
Pritchard E, Vihta KD, Lipworth S
… +10 more, Pouwels KB, Stoesser N, Hope R, Muller-Pebody B, Quan TP, Cregan J, Brown C, Hopkins S, Eyre DW, Walker AS
OBJECTIVES: Escherichia coli bacteraemias have been under mandatory surveillance in the UK for fifteen years, but cases continue to rise. Systematic searches of all features present within electronic healthcare records (...OBJECTIVES: Escherichia coli bacteraemias have been under mandatory surveillance in the UK for fifteen years, but cases continue to rise. Systematic searches of all features present within electronic healthcare records (EHRs), described here as an EHR-wide association study (EHR-WAS), could potentially identify under-appreciated factors that could be targeted to reduce infections. METHODS: We used data from Oxfordshire, UK, and an EHR-WAS method developed for use with large-scale COVID-19 data to estimate associations between E. coli bacteraemia cases, hospital-exposed controls, and 377 potential risk factors using Poisson regression models adjusted for potential confounders for three two-year financial year (FY) periods. RESULTS: FY2022/23-2023/24 analysis included 757 (0.3%) cases and 276,758 (99.7%) controls. We identified six broad disease areas associated with increased or decreased E. coli bacteraemia risk. Renal/urological/urinary tract infection-related variables had the largest impact, with 47% of cases theoretically removed if these factors could be minimised. Cancer-related variables were associated with higher E. coli bacteraemia risk (1.20 times higher (95%CI 1.08-1.34) per three months closer to chemotherapy in the last year), as were gastrointestinal- and infectious disease-related variables. Cardiac/respiratory-related variables were associated with lower E. coli bacteraemia risk, whereas greater healthcare exposure showed no consistent effect. Associated factors varied across periods, but broad groups remained similar. CONCLUSIONS: Applying an EHR-WAS approach, we show E. coli bacteraemias are largely driven by known risk factors and frailty, highlighting the importance of monitoring these factors and targeting modifiable risks where possible.
Baker MA, Klompas M, Blaeser EM
… +12 more, Rhee C, Abdulhayoglu E, Cadogan J, Flanigan E, Pearson Z, Taffner S, Winkler M, Boire N, Worley J, Brigl M, Bry L, Pecora N
BACKGROUND: Conventional surveillance methods may miss healthcare-associated pathogen transmission, particularly for common, drug-susceptible organisms. It is unclear if prospective genomic analyses can help identify oth...BACKGROUND: Conventional surveillance methods may miss healthcare-associated pathogen transmission, particularly for common, drug-susceptible organisms. It is unclear if prospective genomic analyses can help identify otherwise silent transmission events and inform prevention efforts. METHODS: We sequenced methicillin-susceptible Staphylococcus aureus (MSSA) surveillance and clinical isolates in the neonatal intensive care unit (NICU) of an academic hospital between February 2022 and March 2024. Insights gleaned from genomic-epidemiologic analyses were used to control a large MSSA cluster and to calibrate infection control measures thereafter. FINDINGS: There were 2352 babies admitted during the 26-month study period, of whom 318 became colonized or infected with MSSA. Monthly MSSA incidence rates were largely stable throughout this period, but whole genome sequencing demonstrated 16 MSSA clusters (range 2-19 babies/cluster). Sequencing data integrated with epidemiologic analyses informed escalating infection control measures to control a sustained cluster of 19 babies infected with MSSA ST30 (including increased hand hygiene monitoring, enhanced environmental and equipment cleaning, contact precautions, decolonization of MSSA carriers), a subsequent decision against further intensification (foregoing screening all staff members for MSSA carriage), and the subsequent liberalization of some interventions (dropping contact precautions for lower risk babies). While intensified infection control measures controlled the primary ST30 cluster, low-level transmission events (range 2-8 babies) were detected throughout the study period despite those interventions. INTERPRETATIONS: Integrating prospective genomic and epidemiologic analyses of healthcare-associated pathogens can help identify unrecognized transmission clusters and inform and calibrate infection control response measures. SUMMARY: Prospective genotyping of surveillance and clinical methicillin-susceptible Staphylococcus aureus (MSSA) isolates in a neonatal intensive care unit over a 26-month period identified multiple MSSA clusters that were otherwise unappreciated and helped to both catalyze and calibrate infection control measures.
BACKGROUND: To investigate the genetic diversity, evolutionary dynamics, and phylogeography of DENV strains circulating in Saudi Arabia. METHODS: We conducted serotyping, whole-genome sequencing, and phylogeographic anal...BACKGROUND: To investigate the genetic diversity, evolutionary dynamics, and phylogeography of DENV strains circulating in Saudi Arabia. METHODS: We conducted serotyping, whole-genome sequencing, and phylogeographic analyses of DENV strains collected across Saudi Arabia between 2021 and 2023. A total of 20 full genomes were successfully obtained: DENV-1 (n = 2), DENV-2 (n = 10), and DENV-3 (n = 8). RESULTS: Serotyping revealed co-circulation of DENV-1, DENV-2, and DENV-3, with DENV-2 emerging as the predominant serotype. Phylogeographic analysis of whole genomes identified at least five distinct introductions of DENV-2 genotype II into Saudi Arabia, primarily originating from India, Sri Lanka and Pakistan. The earliest introduction was estimated around 13 June 1985 (95% HPD: 5 June 1983 to 11 September 1986). DENV-1 genotype III, undetected for over two decades, re-emerged in Jazan and was likely introduced from Djibouti (TMRCA: 27 July 2018; 95% HPD: 9 December 2017 to 21 March 2019). Two independent introductions of DENV-3 genotype III were identified, originating from Malaysia and India, with TMRCA estimates ranging from 2007 to 2011-indicating at least a decade of undetected circulation. CONCLUSIONS: Our findings highlight Saudi Arabia's evolving role as a regional hub for DENV transmission, driven by mass gatherings and labor migration. Strengthening genomic surveillance, enhancing vector control, and fostering regional data sharing are critical to improving outbreak response and preparedness.
Cai X, Wang X, Ni H
… +16 more, Zhou J, Liang Y, Yao Y, Fang X, Dai T, Wang L, Fang L, Chen Y, Wu Y, Wu B, Zhang W, Zhang R, Pei S, Liu X, Hao Y, Guo P
OBJECTIVES: In recent decades, China has experienced successive epidemics of seasonal Japanese encephalitis (JE), with the Japanese encephalitis virus (JEV) particularly spreading continuously in rural and suburban areas...OBJECTIVES: In recent decades, China has experienced successive epidemics of seasonal Japanese encephalitis (JE), with the Japanese encephalitis virus (JEV) particularly spreading continuously in rural and suburban areas. METHODS: Nationwide data on 9061 JE cases, mosquito abundance from 89 surveillance sites, and population movement between 337 cities during 2013-19 were obtained. Seasonal multivariate linear regression models including time trends and reconciliation terms representing annual and semiannual cycles were fitted to the weekly time series of JE cases, and the amplitude and peak time of the cycles were estimated. A metapopulation network model of inter-city population mobility coupled with an iterative Bayesian inference algorithm was established to simulate the epidemic dynamics of JEV and estimate the time-varying transmission parameters. RESULTS: The timing of the annual peak of JEV epidemics varied with latitude (p-value < 0.05), mainly characterized by earlier in southern cities and later in northern cities. There was no significant difference in the annual amplitude fluctuations of JEV epidemics in different latitudes (p-value > 0.05). Regions with higher values of effective reproduction number R were mainly concentrated in central China, including Sichuan, Chongqing and Shaanxi provinces, with the annual activity peak typically occurring around August. Infections caused by population mobility mainly occurred in hub cities with high connectivity and radiated to surrounding cities. CONCLUSIONS: Findings from this nationwide study can help enhance situational awareness of the spread of JE and inform appropriate intervention strategies to advance the goal of JE elimination.
BACKGROUND: In 2025, Pune, India, witnessed an unprecedented surge in Guillain-Barré Syndrome (GBS) cases, raising urgent public health concerns. GBS, a rare neurological condition often linked to infections, demanded im...BACKGROUND: In 2025, Pune, India, witnessed an unprecedented surge in Guillain-Barré Syndrome (GBS) cases, raising urgent public health concerns. GBS, a rare neurological condition often linked to infections, demanded immediate epidemiological and molecular scrutiny. Evidence from earlier studies points to infectious agents like Campylobacter jejuni, cytomegalovirus, and enteric viruses as common triggers. Environmental conditions and regional pathogen variations were considered potential contributors to the outbreak. To uncover the cause, a broad molecular screening was initiated to detect any known or emerging infectious agents. METHODS: A comprehensive molecular screening was conducted for 19 pathogens, including established GBS-linked and enteric pathogens. Advanced genomic techniques, including phylogenetic and mutation analysis, were employed to characterize the detected pathogens. FINDINGS: Two major pathogens, Campylobacter jejuni and Norovirus, were identified by using molecular methods. Whole-genome sequencing of 12 representative strains using a genotyping tool revealed their classification into genogroup II within three major genotypes: GII.16[P16] (n=9, GBS-associated), GII.17[P17] (n=2), and GII.4 Sydney[P16] (n=1). Phylogenetic analysis based on VP1 and RdRp genes confirmed genotyping and revealed that all norovirus strains from GBS patients clustered within a potential distinct Indian sub-lineage, closely related to strains reported from Russia, USA and Germany, suggesting possible global dissemination. The GII.17 strains belonged to the globally dominant Romania-2021-like lineage, while the GII.4 strain clustered with the pandemic Sydney[P16] variants. Mutation analysis revealed genotype-specific patterns. GII.17 strains had the highest number of non-synonymous mutations (>160), mostly in ORF1 (RdRp; RNA-dependent RNA polymerase), suggesting replication adaptation. In contrast, GBS-associated GII.16 strains showed increased mutations in ORF2 (VP1; major capsid protein), likely driven by immune selection pressures. INTERPRETATION: These findings highlight the importance of genomic surveillance to identify emerging norovirus lineages and their potential clinical significance. Continued monitoring is vital to understand norovirus evolution and its possible connection to GBS.
Valentina M, Giulia M, Eleonora C
… +15 more, Alessandro C, Rozenn E, Francesca C, Eleonora T, Jessica P, Giulia M, Aurora B, Stefania N, Alessandro G, Licia B, Simona G, Andrea S, Enrico G, Fabrizio M, Andrea A
BACKGROUND: In 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health rest...BACKGROUND: In 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health restrictions by late 2021 frequently led to infection, rather than vaccine, as a third exposure. OBJECTIVE: To compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses. METHODS: We compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. Immune profiles were evaluated using live virus neutralization assays, IFN-γ ELISpot, Luminex assay, flow cytometry and mass cytometry. RESULTS: Both total anti-Spike IgG and variant-specific neutralising antibodies were comparable following infection or vaccine as a third exposure. Overall, T cell populations were similar but functionally different. CD8⁺ Effector Memory (TEM) cells in the vaccine group showed higher expression of CD69 and Granzyme B following stimulation with SARS-CoV-2 Spike peptides. In contrast, the hybrid group produced higher levels of innate immune associated cytokines IL-10 and IL-34, as well as the T cell homing chemokine CCL25, after stimulation. CONCLUSIONS: While both exposures generated comparable breadth of protection against SARS-CoV-2 variants, our findings suggest that the route of third exposure influences different aspects of the immune response, warranting further investigation into long-term immunity at both systemic and mucosal sites.
BACKGROUND: Candida glabrata is an opportunistic human fungal pathogen causing infections due to its innate antifungal drug resistance and ability to adhere to mucocutaneous surfaces. Epigenetic pathways may be important...BACKGROUND: Candida glabrata is an opportunistic human fungal pathogen causing infections due to its innate antifungal drug resistance and ability to adhere to mucocutaneous surfaces. Epigenetic pathways may be important factors in the development of drug resistance. Our previous studies showed that deubiquitination of H2B, regulated by a module comprised of Ubp8, Sgf11, Sgf73, and Sus1, plays important roles in oxidative stress tolerance and biofilm formation of C. glabrata. However, the roles of the Rad6 and Bre1 ligase in regulating the ubiquitination of H2B in C. glabrata remain unclear. METHODS: We characterized the functions of Rad6 and Bre1 in C. glabrata by generating deletion mutants (rad6, bre1, and rad6 bre1). We analyzed biofilm formation, gene expression of key adhesins (EPA1, EPA6, EPA20) and protease (YPS4), antifungal drug susceptibility, stress responses, and virulence in a murine model of systemic candidiasis. RESULTS: Deletion of RAD6 and BRE1 resulted in enhanced biofilm formation, correlating with upregulation of key adhesin genes and the protease gene YPS4. The mutants showed distinct patterns of antifungal drug susceptibility: rad6 and rad6 bre1 mutants exhibited increased sensitivity to azoles, while bre1 mutant showed enhanced resistance to azoles in solid YPD agar plates but no significant difference in liquid RPMI medium. All mutants demonstrated decreased resistance to echinocandins and amphotericin B, associated with altered expression of ergosterol biosynthesis genes (ERG11) and glucan synthase genes (FKS1, FKS2). The mutants also displayed decreased resistance to oxidative and cell wall stresses despite elevated basal expression of antioxidant genes (SOD1, GPX2, CTA1). In a murine model of systemic candidiasis, both rad6 and bre1 mutants exhibited enhanced virulence compared to the wild type. CONCLUSION: Rad6 and Bre1 in C. glabrata function as negative regulators of biofilm formation and adhesion, and their related-genes expression, while RAD6 deletion also suppresses macrophage ROS production and enhances fungal survival. The enhanced virulence observed in the rad6 and bre1 mutants is primarily attributed to these combined effects of increased biofilm formation, enhanced adhesion capability, and macrophage immune evasion.
BACKGROUND: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk...BACKGROUND: Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination. METHODS: We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list. RESULTS: Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96-313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18-69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85-88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27-74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23-1.29) for unvaccinated and 1.08 (95% CI: 1.05-1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups. INTERPRETATION: COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.
BACKGROUND: Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced to prevent infant RSV-related hospitalizations. Although efficacy has been demonstrated in clin...BACKGROUND: Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced to prevent infant RSV-related hospitalizations. Although efficacy has been demonstrated in clinical trials, real-world data on targeted immunization strategies remain limited. We aimed to evaluate the effectiveness of nirsevimab in preventing RSV-associated hospitalizations in infants under 12 months, within a seasonal program prioritizing infants born from April onwards. METHODS: We conducted a prospective, multicenter, matched case-control study across seven Italian hospitals during the 2024-2025 RSV season. Infants hospitalized with PCR-confirmed RSV bronchiolitis were matched 1:2 by age and date of admission to controls hospitalized for non-respiratory causes. Data were collected via electronic medical records. Immunization effectiveness (IE) was estimated using conditional logistic regression adjusted for sex assigned at birth, gestational age, birth weight, and clinical risk factors. Two pre-specified stratified analyses and a sensitivity analysis using inverse probability of treatment weighting (IPTW) were performed. RESULTS: A total of 138 infants were included (46 cases, 92 controls). Adjusted IE was 89.5% (95% CI: 60.3-97.2%). Stratified analyses yielded similar results among infants born after April 1 (IE: 88.4%, 95% CI: 56.5-96.9%) and those without risk factors (IE: 88.1%, 95% CI: 45.7-97.4%). IPTW analysis confirmed protection (IE: 79.6%, 95% CI: 53.5-91.0%). CONCLUSIONS: This study provides real-world evidence supporting the effectiveness of nirsevimab in a targeted seasonal immunization framework. These findings may inform phased implementation strategies and RSV prophylaxis policies in varied healthcare settings.
Downs LO, Delphin M, van Schalkwyk M
… +20 more, Hugo S, Lumley SF, Waddilove E, Wang T, Martin J, de Lara C, Babbs A, Andersson MI, Glashoff RH, Ansari MA, Agarwal K, Dusheiko G, Taljaard J, Preiser W, Barnes E, Kelly G, Carey I, Shimakawa Y, Maponga TG, Matthews PC
OBJECTIVES: We set out to evaluate Hepatitis B core-related antigen (HBcrAg) as a proxy for hepatitis B (HBV) viral load (VL) and liver disease in two different population settings. METHODS: We undertook a cross-sectiona...OBJECTIVES: We set out to evaluate Hepatitis B core-related antigen (HBcrAg) as a proxy for hepatitis B (HBV) viral load (VL) and liver disease in two different population settings. METHODS: We undertook a cross-sectional retrospective observational study using samples and data from adults living with chronic HBV infection from the United Kingdom (UK, n=142) and South Africa (SA, n=211). We assessed HBcrAg distribution, relationship with other biomarkers, and risk stratification performance, applying point of care test (POCT) thresholds. RESULTS: SA and UK cohorts differed by ethnicity, HIV coinfection, HBeAg-positivity and proportion with HBV VL >200,000 IU/ml (all p<0.001). HBcrAg positively correlated with alanine aminotransferase (ALT) (in both settings p<0.01), and fibrosis/cirrhosis by APRI score (p=0.03 in UK, p=0.008 in SA), but not with elastography or FIB-4 scores. HBcrAg ≥4.3 log10U/ml (POCT threshold) was 100% sensitive and 92% specific for predicting VL >200,000 IU/ml in the UK cohort, compared to 94% sensitive and 86% specific in the SA population. CONCLUSIONS: HBcrAg correlated with VL, but less so with liver disease. Use of this biomarker needs tailoring for use in diverse populations.
OBJECTIVES: Accurate diagnosis of sepsis is needed to initiate life-saving treatment decisions. Biomarkers capable of identifying both acute infection and sepsis are required to assist clinicians. METHODS: A real-life he...OBJECTIVES: Accurate diagnosis of sepsis is needed to initiate life-saving treatment decisions. Biomarkers capable of identifying both acute infection and sepsis are required to assist clinicians. METHODS: A real-life heterogeneous cohort of 388 patients with suspected acute infections was recruited at presentation to the ED. Nine emerging host-response biomarkers (MyD88, MMP-8, leptin, ENA-78, fractalkine, PD- L1, pentraxin-3, TRAIL, and GLP-1) were quantified using a multiparameter assay. We performed AUROC analysis for the endpoints bacterial infection, sepsis, and 30-day mortality. We further assessed diagnostic performance when combining these biomarkers using a machine learning algorithm. RESULTS: Particularly, MyD88, PD-L1, and pentraxin-3 presented high AUROCs for the endpoints bacterial infection (≥0.87), sepsis (≥0.81), and 30-day mortality (≥0.71). Seven out of the nine investigated biomarkers showed statistically significant discrimination for all three endpoints. A combined algorithm via the XGBoost model using pentraxin-3, MyD88, and GLP-1 was used for sepsis prediction, with an AUROC of 0.89, higher than clinical assessment via NEWS-2 (0.83) or procalcitonin (0.81). CONCLUSION: Pentraxin-3, MyD88, GLP-1, and PD-L1 are a promising complementary set of biomarkers for risk assessment and stratification. When a trained multiparameter classifier is used, the combination of biomarkers results in a valid tool for sepsis diagnosis. TRIAL REGISTRATION: DRKS00020521, DRKS00017395.