Role of biomarkers in antimicrobial stewardship: physicians' perspectives.

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1ß/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.

Efficient detection of nitric oxide a biomarker associated with COVID19 via N, P co-doped C60 fullerene: a computational study.

CONTEXT: Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0 kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103 s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection. METHODS: The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.

Hematological Parameters and Comorbidities in COVID-19: Insights into Clinical Profiles and Outcome Predictors.

BACKGROUND: The global pandemic, known as the coronavirus disease 2019 (COVID-19) and caused by the severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), poses a significant threat, particularly to individuals with comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), diabetes, HIV, cardiovascular disease (CVD), and cancer. METHODS: This descriptive retrospective study investigates the impact of comorbidities on COVID-19-positive patients. The study includes individuals that were tested positive for SARS-CoV-2 via polymerase chain reaction at the Security Forces Hospital, Makkah, KSA, between February, 2022, and June, 2022. A total of 208 patients (107 males, 101 females) were examined, and the laboratory results revealed normal parameters. RESULTS: An analysis indicates that 86.5% of the patients were discharged, 2.9% remained hospitalized, and 10.6% succumbed to the disease, indicating a 10.6% mortality rate among comorbid COVID-19-positive patients. Notably, the study identifies specific comorbidities (chronic kidney disease, diabetes mellitus, hypertension) and changes in laboratory parameters (red blood cells, hemoglobin, C-reactive protein, white blood cells, ferritin, D-dimer, ALT, troponin, LDH, neutrophils) associated with ICU admission during hospitalization. CONCLUSIONS: This study underscores the critical impact of comorbidities, such as chronic kidney disease, diabetes, and hypertension, on the clinical outcomes of COVID-19-positive patients. The identification of specific laboratory parameters linked with ICU admission provides valuable insights for risk stratification and tailored management strategies.

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Strategic Retesting to Reduce False Positive SARS-CoV-2 PCR Test Results.

BACKGROUND: Nucleic acid amplification testing is the gold standard for SARS-CoV-2 diagnostics, although it may produce a certain number of false positive results. There has not been much published about the characteristics of false positive results. In this study, based on retesting, specimens that initially tested positive for SARS-CoV-2 were classified as true or false positive groups to characterize the distribution of cycle threshold (CT) values for N1 and N2 targets and number of targets detected for each group. METHODS: Specimens that were positive for N-gene on retesting and accompanied with S-gene were identified as true positives (true positive based on retesting, rTP), while specimens that retested negative were classified as false positives (false positive based on retesting, rFP). RESULTS: Of the specimens retested, 85/127 (66.9%) were rFP, 16/47 (34.0%) specimens with both N1 and N2 targets initially detected were rFP, and the CT values for each target was higher in rFP than in rTP. ROC curve analysis showed that optimal cutoff values of CT to differentiate between rTP and rFP were 34.8 for N1 and 33.0 for N2. With the optimal cutoff values of CT for each target, out of the 24 specimens that were positive for both N1 and N2 targets and classified as rTP, 23 (95.8%) were correctly identified as true positives. rFP specimens had a single N1 target in 52/61 (85.2%) and a single N2 target in 17/19 (89.5%). Notably, no true positive results were obtained from any specimens with only N2 target detected. CONCLUSIONS: These results suggest that retesting should be performed for positive results with a CT value greater than optimal cutoff value for each target or with a single N1 target amplified, considering the possibility of a false positive. This may provide guidance on indications to perform retesting to minimize the number of false positives.

Contributing Factors Affecting the Length of Hospital Stay among Febrile Patients with Omicron Reported in Suzhou.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had global attention with regard to the urgent challenging threat to global public health. Currently, the novel Omicron variant is showing rapid transmission across the world, which appears to be more contagious than the previous variants of COVID-19. Early recognition of disease is critical for patients' prognosis. Fever is the most common symptom. We evaluated the clinical characteristics of febrile patients with COVID-19 reported in Suzhou and explored the predictors for a longer duration of hospitalization in febrile patients. METHODS: This retrospective study was carried out in 146 Omicron variant infected patients confirmed by nucleic acid tests in the Affiliated Infectious Hospital of Soochow University between February 13, 2022 and March 2, 2022. Data of febrile and afebrile laboratory-confirmed patients on hospital admission in Suzhou were collected and compared. According to the median length of stay (LOS), febrile cases were divided into short and long LOS groups. Then the predictive factors for a prolonged duration of hospitalization were analyzed using logistic regression methods. Receiver Operating Characteristic (ROC) Curve analysis was used to analyze the effectiveness of the risk factors for prolonged duration of hospitalization in febrile COVID-19 patients. RESULTS: Of the 146 discharged patients in our study, 112 patients (76.7%) caught a fever. Compared to afebrile Omicron patients, febrile patients showed a significantly longer duration of hospitalization (15.00 (5.80) vs. 13.00 (6.00), p = 0.002). Taking the median LOS (15 days) as the dividing point, 64 febrile cases were assigned to the short LOS group and the rest to the long LOS group. The long LOS group had a longer virus shedding duration than the short LOS group (18.42 ± 2.86 vs. 11.94 ± 2.50 days, p < 0.001). Compared to short LOS febrile patients, long LOS patients were older (44.88 ± 21.36 vs. 30.89 ± 17.95 years, p < 0.001) and showed a higher proportion of greater than 60 years old (33.3% vs. 9.4%, p = 0.002; Supplemental Table S2). Febrile patients with long LOS also showed a higher proportion of hypertension (25% vs. 6.3%, p = 0.005) and higher levels of cTnI (5.00 (3.00) vs. 4.00 (2.00) µg/L, p = 0.025). The multivariate analysis indicated that virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was the independent risk factor associated with long-term hospital stay in febrile patients with Omicron. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for virus shedding duration to diagnose prolonged duration of hospitalization in febrile COVID-19 patients was 0.951 (95% CI 0.913 - 0.989). The cutoff point was set at 14.5 days. CONCLUSIONS: More than half of the non-severe patients exposed to the new Omicron variant had symptoms of fever. In total, 42.86% of the febrile patients were discharged within 15 days since hospital admission. Febrile Omicron cases took a longer duration of hospitalization compared to afebrile patients, and virus shedding duration (OR 2.369, 95% CI 1.684 - 3.333, p < 0.001) was probably a predictive factor for long-term hospital stays.

A Prediction Model for Prolonged Hospital Length of Stay (ProLOS) in Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers. METHODS: The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. RESULTS: The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits. CONCLUSIONS: A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

Optical biosensors for diagnosis of COVID-19: nanomaterial-enabled particle strategies for post pandemic era.

The COVID-19 pandemic underlines the need for effective strategies for controlling virus spread and ensuring sensitive detection of SARS-CoV-2. This review presents the potential of nanomaterial-enabled optical biosensors for rapid and low-cost detection of SARS-CoV-2 biomarkers, demonstrating a comprehensive analysis including colorimetric, fluorescence, surface-enhanced Raman scattering, and surface plasmon resonance detection methods. Nanomaterials including metal-based nanomaterials, metal-organic frame-based nanoparticles, nanorods, nanoporous materials, nanoshell materials, and magnetic nanoparticles employed in the production of optical biosensors are presented in detail. This review also discusses the detection principles, fabrication methods, nanomaterial synthesis, and their applications for the detection of SARS-CoV-2 in four categories: antibody-based, antigen-based, nucleic acid-based, and aptamer-based biosensors. This critical review includes reports published in the literature between the years 2021 and 2024. In addition, the review offers critical insights into optical nanobiosensors for the diagnosis of COVID-19. The integration of artificial intelligence and machine learning technologies with optical nanomaterial-enabled biosensors is proposed to improve the efficiency of optical diagnostic systems for future pandemic scenarios.

Low TSH and low T3 hormone levels as a prognostic for mortality in COVID-19 intensive care patients.

Introduction: Coronavirus diasease 2019 (COVID-19) can cause both pulmonary and systemic inflammation, potentially determining multi-organ dysfunction. The thyroid gland is a neuroendocrine organ that plays an important role in regulating immunity and metabolism. Low serum levels of thyroid hormones are common in critical disease situations. The association between low thyroid hormone levels and mortality in COVID-19 intensive care patients has yet to be studied. Aim: The aim of this study is to compare thyroid hormone levels between patients in the general intensive care unit (ICU) to patients in the COVID-19 ICU. Methods: This was a retrospective comparative study of 210 patients who were hospitalized at Ziv Medical Center in the general ICU and in the COVID-19 ICU. Clinical and demographic data were collected from patient's electronic medical records. Results: Serum thyroid hormone levels of Thyroid Simulating Hormone (TSH), T4, and T3 were significantly lower in COVID-19 intensive care unit patients compared to the patients from the general intensive care unit (p < 0.05). The mortality rate in the COVID-19 ICU (44.4%) was higher compared to that in the general ICU (27.3%) (p < 0.05). No significant statistical difference was observed between the two groups in terms of gender and recorded comorbidities of diabetes mellitus, cerebral vascular accident, kidney disease, and cancer. Conclusions: Low serum thyroid hormone levels-T3, T4, and TSH-in COVID-19 ICU patients are associated with higher mortality and could possibly be used as a prognostic factor for mortality among COVID-19 ICU patients. Thyroid hormone levels should be a part in the routine evaluation of COVID-19 ICU patients.

Clinical characteristics of liver transplant recipients with COVID-19 and analysis of risk factors for the severe disease.

INTRODUCTION: Liver transplant (LT) recipients were at a high risk of infection during the coronavirus disease 2019 (COVID-19) pandemic. Our purpose was to compare the clinical characteristics of severe and non-severe groups of LT recipients with COVID-19, and to analyze their risk factors for severe disease. METHODOLOGY: 79 LT recipients with COVID-19 were divided into a non-severe group (n = 60) and a severe group (n = 19), and differences in clinical characteristics, laboratory tests, and chest computed tomography (CT) performance were analyzed. Logistic regression was used to identify risk factors with severe COVID-19. Receiver operating characteristic (ROC) curves were plotted and the area under curve (AUC) values were calculated to assess the predictive value for severe COVID-19. RESULTS: Age was statistically different (p < 0.001) between the two groups. The difference in neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), D-dimer, urea, C-reactive protein (CRP), lactate dehydrogenase (LDH), and the number of lung segments involved in inflammation between the two groups were statistically significant (p < 0.05). The results revealed that age (OR = 1.255, 95% CI 1.079-1.460), NLR (OR = 1.172, 95% CI 1.019-1.348), and Scr (OR = 1.041, 95% CI 1.016-1.066) were independent risk factors for severe COVID-19. The ROC results showed that high values for age, NLR and Scr predicted severe COVID-19, with AUC values of 0.775, 0.841 and 0.820, respectively, and 0.925 for the three factors combined. CONCLUSIONS: Advanced age, and elevated NLR and Scr are independent risk factors for severe COVID-19 in LT recipients.

Logistic regression analysis of the value of biomarkers, clinical symptoms, and imaging examinations in COVID-19 for SARS-CoV-2 nucleic acid detection.

The detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleic acid detection provides a direct basis for diagnosing Coronavirus Disease 2019. However, nucleic acid test false-negative results are common in practice and may lead to missed diagnosis. Certain biomarkers, clinical symptoms, and imaging examinations are related to SARS-CoV-2 nucleic acid detection and potential predictors. We examined nucleic acid test results, biomarkers, clinical symptoms, and imaging examination data for 116 confirmed cases and asymptomatic infections in Zhuhai, China. Patients were divided into nucleic acid-positive and -false-negative groups. Predictive values of biomarkers, symptoms, and imaging for the nucleic acid-positive rate were calculated by Least Absolute Shrinkage and Selection Operators regression analysis and binary logistic regression analysis, and areas under the curve of these indicators were calculated. Hemoglobin (OR = 1.018, 95% CI: 1.006-1.030; P = .004) was higher in the respiratory tract-positive group than the nucleic acid-negative group, but platelets (OR = 0.996, 95% CI: 0.993-0.999; P = .021) and eosinophils (OR = 0.013, 95% CI: 0.001-0.253; P = .004) were lower; areas under the curve were 0.563, 0.614, and 0.642, respectively. Some biomarkers can predict SARS-CoV-2 viral nucleic acid detection rates in Coronavirus Disease 2019 and are potential auxiliary diagnostic tests.

Is it possible to identify COVID-19 infection-related biomarkers during pregnancy?: A prospective study in Turkish population.

The coronavirus disease 2019 (COVID-19) has raised concerns about the potential complications it may cause in pregnant women. Therefore, biomarkers that can predict the course of COVID-19 in pregnant women may be of great benefit as they would provide valuable insights into the prognosis and, thus, the management of the disease. In this context, the objective of this study is to identify the biomarkers that can predict COVID-19 progression in pregnant women, focusing on composite hemogram parameters and systemic inflammatory and spike markers. The population of this single-center prospective case-control study consisted of all consecutive pregnant women with single healthy fetuses who tested positive for COVID-19 and who were admitted to Bakirköy Dr Sadi Konuk Training and Research Hospital in Istanbul, Turkey, a COVID-19 referral hospital, between April 2020 and March 2021, with an obstetric indication, during their second or third trimester. The control group consisted of consecutive pregnant women with a single healthy fetus who were admitted to the same hospital within the same date range, had demographic and obstetric characteristics matching the patient group, but tested negative for COVID-19. The patient and control groups were compared in terms of platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and neutrophil-to-lymphocyte ratio (NLR), and systemic inflammatory and spike markers, including C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), cluster of differentiation 26 (CD26), and B7 homolog 4 (B7H4). There were 45 (51.1%) and 43 (48.8%) pregnant women in the patient and control groups, respectively. There was no significant difference between the groups in demographic and obstetric characteristics (P > .05). The PNR, PLR, and CRP values were significantly higher in the patient group than in the control group (P < .05). On the other hand, there was no significant difference between the groups in IL-6, IL-10, CD26, and B7H4 levels (P > .05). The findings of our study showed that specific inflammatory markers, such as CRP, PLR, and PNR, can potentially predict the course of COVID-19 in pregnant women. However, more comprehensive, well-controlled studies are needed to corroborate our study's findings and investigate other potential inflammatory markers.

[VASCULAR OPHTHALMIC MANIFESTATIONS IN COVID-19 PATIENTS].

INTRODUCTION: Although COVID-19 is mainly a respiratory disease, recent evidence has emerged of vascular and procoagulant pathologies even in young and otherwise healthy individuals. Ophthalmic manifestations include, among others, visual impairment due to arteritic and venous retinal obstructions, which at times precedes other aspects of the disease. We present two atypical cases of internal carotid dissection (ICAD) and review the different ocular symptoms of ICAD and its association with the COVID-19 pandemic. BACKGROUND: A 43-year-old otherwise healthy man was referred to the Emergency Department with a headache and monocular blurring of vision. A recent fever (2 weeks prior) was noted on anamnesis, in light of absence of available positive PCR test during the illness period, clinical suspicion of COVID-19 was assumed. An initial ophthalmic evaluation found a mild optic nerve function impairment with preserved visual acuity. Computed tomography (CT) showed sinusitis, and an initial diagnosis was made of mild optic neuropathy secondary to sphenoid sinusitis. A few hours after admission, the patient reported deterioration of symptoms and examination revealed no light perception in his right eye and pale edematous optic nerve. Urgent magnetic resonance angiography (MRA) demonstrated right ICAD with no additional findings. The second patient, a 43-year-old man developed an acute event of strabismus, left limb paralysis, and speech difficulties while on a hospital visit for his son. The patient underwent CT of the brain which demonstrated extensive infarction following the distribution of his right cerebral artery. Continued investigation using computed tomography angiography (CTA) demonstrated a dissection of the right internal carotid artery. The patient was positive for COVID-19. DISCUSSION: In this review, we discuss 2 cases of carotid artery dissection presenting with an acute ocular complaint in two otherwise healthy young individuals. Events were suspected to have been provoked by COVID-19 infection. The pathogenesis and mechanisms behind COVID-19 induced coagulopathy are not clear, and several mechanisms have been proposed including endothelial damage and dysfunction. The virus is thought to enter endothelial cells and lead to a pathological procoagulant state. Awareness should be drawn to uncommon signs especially in young adults. Clotting issues can arise and should be treated quickly as they might be life and vision threatening.

Evaluation of blood pressure variation in recovered COVID-19 patients at one-year follow-up: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has various sequelae, one of which might be hypertension. We aimed to evaluate COVID-19's impact on blood pressure (BP) in non-hospitalized patients at one-year follow-up. METHOD: A total of 7,950 consecutive COVID-19 patients regularly visiting our cardiology clinic were retrospectively screened. Patients' electronic medical records including demographics, comorbidities, vital signs, treatments, and outcomes, were reviewed by two physicians. Individuals with at least one BP measurement in the three months preceding COVID-19 and one measurement in 12 months or more following recovery were included. BP levels before and after COVID-19 were compared using the paired t-test. RESULTS: 5,355 confirmed COVID-19 patients (mean age 55.51 ± 15.38 years) were included. Hypertension (56.9%) and diabetes mellitus (34%) were the predominant comorbidities, and 44.3% had prior major adverse cardiovascular events. Both systolic (126.90 ± 20.91 vs. 139.99 ± 23.94 mmHg, P < 0.001) and diastolic BP (80.54 ± 13.94 vs. 86.49 ± 14.40 mmHg, P < 0.001) were significantly higher post-COVID-19 vs. pre-COVID-19. Notably, 456 (14%) hypertensive patients experienced exacerbated hypertension, while 408 (17%) patients developed new-onset hypertension, overall 864 (16%) of patients had exacerbation or new hypertension. Linear regression analysis revealed that advanced age, smoking, previous cardiovascular events, hypertension, and diabetes mellitus predict increased BP following COVID-19 (P < 0.001). CONCLUSION: COVID-19 raised systolic and diastolic BP in the long term in non-hospitalized patients, with over one-sixth developing new-onset or exacerbated hypertension. All patients should be evaluated regarding BP, following COVID-19 recovery, particularly those with the mentioned predictive factors. (clinicaltrial.gov: NCT05798208).

Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation.

BACKGROUND: Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. METHODS: All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. RESULTS: 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. CONCLUSION: OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.

Biolayer-Interferometry-Guided Functionalization of Screen-Printed Graphene for Label-Free Electrochemical Virus Detection.

Additive manufacturing holds promise for rapid prototyping and low-cost production of biosensors for diverse pathogens. Among additive manufacturing methods, screen printing is particularly desirable for high-throughput production of sensing platforms. However, this technique needs to be combined with carefully formulated inks, rapid postprocessing, and selective functionalization to meet all requirements for high-performance biosensing applications. Here, we present screen-printed graphene electrodes that are processed with thermal annealing to achieve high surface area and electrical conductivity for sensitive biodetection via electrochemical impedance spectroscopy. As a proof-of-concept, this biosensing platform is utilized for electrochemical detection of SARS-CoV-2. To ensure reliable specificity in the presence of multiple variants, biolayer interferometry (BLI) is used as a label-free and dynamic screening method to identify optimal antibodies for concurrent affinity to the Spike S1 proteins of Delta, Omicron, and Wild Type SARS-CoV-2 variants while maintaining low affinity to competing pathogens such as Influenza H1N1. The BLI-identified antibodies are robustly bound to the graphene electrode surface via oxygen moieties that are introduced during the thermal annealing process. The resulting electrochemical immunosensors achieve superior metrics including rapid detection (55 s readout following 15 min of incubation), low limits of detection (approaching 500 ag/mL for the Omicron variant), and high selectivity toward multiple variants. Importantly, the sensors perform well on clinical saliva samples detecting as few as 103 copies/mL of SARS-CoV-2 Omicron, following CDC protocols. The combination of the screen-printed graphene sensing platform and effective antibody selection using BLI can be generalized to a wide range of point-of-care immunosensors.