Low Severity Disease Research Articles

Mass Spectrometry-Based Metabolomics Reveals a Salivary Signature for Low-Severity COVID-19

Omics approaches were extensively applied during the coronavirus disease 2019 (COVID-19) pandemic to understand the disease, identify biomarkers with diagnostic and prognostic value, and discover new molecular targets for medications. COVID-19 continues to challenge the healthcare system as the virus mutates, becoming more transmissible or adept at evading the immune system, causing resurgent epidemic waves over the last few years. In this study, we used saliva from volunteers who were negative and positive for COVID-19 when Omicron and its variants became dominant. We applied a direct solid-phase extraction approach followed by non-target metabolomics analysis to identify potential salivary signatures of hospital-recruited volunteers to establish a model for COVID-19 screening. Our model, which aimed to differentiate COVID-19-positive individuals from controls in a hospital setting, was based on 39 compounds and achieved high sensitivity (85%/100%), specificity (82%/84%), and accuracy (84%/92%) in training and validation sets, respectively. The salivary diagnostic signatures were mainly composed of amino acids and lipids and were related to a heightened innate immune antiviral response and an attenuated inflammatory profile. The higher abundance of thyrotropin-releasing hormone in the COVID-19 positive group highlighted the endocrine imbalance in low-severity disease, as first reported here, underscoring the need for further studies in this area.

Visceral adipose tissue volume effect in Crohn's disease using reduced exposure CT enterography.

The purpose of this investigation was to assess the effect of visceral adipose tissue volume (VA) on reader efficacy in diagnosing and characterizing small bowel Crohn's disease using lower exposure CT enterography (CTE). Secondarily, we investigated the effect of lower exposure and VA on reader diagnostic confidence. Prospective paired investigation of 256 CTE, 129 with Crohn's disease, were reconstructed at 100% and simulated 50% and 30% exposure. The senior author provided the disease classification for the 129 patients with Crohn's disease. Patient VA was measured, and exams were evaluated by six readers for presence or absence of Crohn's disease and phenotype using a 0-10-point scale. Logistic regression models assessed the effect of VA on sensitivity and specificity. The effect of VA on sensitivity was significantly reduced at 30% exposure (odds radio [OR]: 1.00) compared to 100% exposure (OR: 1.12) (p=0.048). There was no statistically significant difference among the exposures with respect to the effect of visceral fat on specificity (p=0.159). The study readers' probability of agreement with the senior author on disease classification was 60%, 56%, and 53% at 100%, 50%, and 30% exposure, respectively (p=0.004). When detecting low severity Crohn's disease, readers' mean sensitivity was 83%, 75%, and 74% at 100%, 50%, and 30% exposure, respectively (p=0.002). In low severity disease, sensitivity also tended to increase as visceral fat increased (ORs per 1000 cm3 increase in visceral fat: 1.32, 1.31, and 1.18, p=0.010, 0.016, and 0.100, at 100%, 50%, and 30% exposure). While the interaction is complex, VA plays a role in detecting and characterizing small bowel Crohn's disease when exposure is altered, particularly in low severity disease.

P07 PCT-targeted ward rounds to reduce inappropriate antibiotic prescribing in medical admissions with suspicion of respiratory tract infections

BackgroundLower respiratory tract infections (LRTIs) are a common reason for antibiotics with unnecessary antibiotic prescribing common because of the difficulties differentiating viral, bacterial and non-infectious mimics of LRTIs (e.g. heart failure) due to similar clinical signs and symptoms.1 Studies of procalcitonin (PCT)- guided antimicrobial stewardship in managing RTI (including community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, acute bronchitis, exacerbation of asthma and sepsis with a suspected respiratory tract infection) in various healthcare settings (primary care, emergency departments, hospital wards and ICUs) have shown it to reduce antibiotic exposure and antibiotic associated side effects without impacting treatment failure, hospital length of stay or negatively impacting on mortality.2 PCT-guided antibiotic stewardship aims to augment clinical decision-making. We wanted to see whether we could use PCT-guided stewardship to safely stop antibiotics in patients with an RTI diagnosis in those with low severity disease and where bacterial infection looks an unlikely cause for the presenting symptoms.3MethodsAn automated daily Excel report sent via e-mail to the antimicrobial pharmacists identified patients with a PCT result and presented the date and levels for PCT, CRP, WBC, any prescribed antibiotics and ward location. Patients with a serum PCT level (<0.25 μg/L) and prescribed respiratory antibiotics were reviewed by one of the antimicrobial pharmacists. All available pathology and radiological results were reviewed on the ward with the patient's clinical signs and symptoms and illness acuity to determine the likelihood of a bacterial cause for symptoms and the risk of early antibiotic cessation. Cases were discussed with the medical team and antibiotics stopped if consensus was achieved. Mortality at 30 days was collected retrospectively for all patients.ResultsBetween June 2020 and January 2022, 120 patients with low PCT and on respiratory antibiotics were reviewed. Antibiotics were stopped in 40 patients (33%). Two patients in the early antibiotic cessation group died within 30 days, both of not infectious causes. By comparison, 11 patients in the continuation group died within 30 days.ConclusionsPharmacist-delivered PCT ward rounds in patients with a clinical suspicion of respiratory infections successfully reduced inappropriate antimicrobial prescribing without negatively impacting 30 day mortality.

Use of machine learning to identify a T cell response to SARS-CoV-2

SummaryThe identification of SARS-CoV-2-specific T cell receptor (TCR) sequences is critical for understanding T cell responses to SARS-CoV-2. Accordingly, we reanalyze publicly available data from SARS-CoV-2-recovered patients who had low-severity disease (n = 17) and SARS-CoV-2 infection-naive (control) individuals (n = 39). Applying a machine learning approach to TCR beta (TRB) repertoire data, we can classify patient/control samples with a training sensitivity, specificity, and accuracy of 88.2%, 100%, and 96.4% and a testing sensitivity, specificity, and accuracy of 82.4%, 97.4%, and 92.9%, respectively. Interestingly, the same machine learning approach cannot separate SARS-CoV-2 recovered from SARS-CoV-2 infection-naive individual samples on the basis of B cell receptor (immunoglobulin heavy chain; IGH) repertoire data, suggesting that the T cell response to SARS-CoV-2 may be more stereotyped and longer lived. Following validation in larger cohorts, our method may be useful in detecting protective immunity acquired through natural infection or in determining the longevity of vaccine-induced immunity.

The prevalence, characteristics and treatment of hemorrhoidal disease: results of an international web-based survey.

Background: This international study assessed the characteristics and treatment of individuals with hemorrhoids. Materials & methods: Online survey among nationally representative populations of adults from Brazil, Czech Republic, France, Hungary, Italy, Romania, Russia and Spain, that identified participants who self-reported having hemorrhoidal disease. Results: Hemorrhoid prevalence was 11% (1725/16015); most respondents had low-severity disease (71%). Compared with the general population, participants with hemorrhoidal disease had more comorbidities (mean 3.1 vs 1.3) and included more women who had been pregnant (81vs 68%). Common initial signs/symptoms were pain (60%), bleeding (47%) and discomfort (43%). Hemorrhoid respondents who consulted a physician were more likely to undergo interventions and take medications. Conclusion: The prevalence of hemorrhoidal disease in the adult population is 11%, mostly low-severity disease.

Oral prevalence and antifungal susceptibility of Candida species in cystic fibrosis patients

ObjectiveThis study aimed at assessing the oral prevalence ofCandida species in cystic fibrosis patients and the antifungal susceptibility of the isolates. DesignOne hundred patients aged 3–20 years old were included in the study and were divided into three groups: G1 (low severity disease): 25 cystic fibrosis patients with Shwachman-Kulczycki score (SK) between 100 and 71; G2 (high severity disease): 25 cystic fibrosis patients with SK score under 40; and G3 (control): 50 healthy patients age- and gender-matched to cystic fibrosis patients. Stimulated saliva samples were collected and the oral fungal concentrations were assessed. Isolates were identified by phenotypic and genotypic tests. Antifungal susceptibilities to amphotericin B, flucytosine and fluconazole were determined by CLSI methodology. Fungal counts were compared by Kruskal Wallis and Dunn’s test (5%). ResultsA total of 68 % of Group 1, 80 % of Group 2, and 44 % of controls yielded positive Candida cultures. Oral concentrations of fungi were significantly higher in cystic fibrosis patients in relation to the control group (p < 0.0005). No significant difference was observed between low and high severity cystic fibrosis groups (p > 0.05). C. albicans was most frequently isolated species in all groups. Higher variability of Candida species was observed in the control group. C. dubliniensis and C. tropicalis were only detected among cystic fibrosis groups. All the isolates were susceptible to flucytosine and fluconazole. ConclusionsPatients with cystic fibrosis were more frequently colonized by Candida species and showed higher oral fungal burden. No antifungal resistant isolates were detected.

Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases.

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age <10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000–2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85–95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8–160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7–20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0–3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2–5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range: $344,029–$799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P<0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre- and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P<0.001), length of stay (P<0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time.