Metagenomic Next-Generation Sequencing of Nasopharyngeal Swabs in Acute Febrile Illness in Cambodia

Background. There is growing recognition of metagenomic next-generation sequencing (mNGS) as a valuable diagnostic tool capable of providing unbiased pathogen detection, but data on performance in low-resource settings remains scant. Here, we use mNGS of nasopharyngeal (NP) swabs taken from subjects in Cambodia to identify potential pathogens causing acute febrile illness. Methods. Febrile subjects aged 2 months to 65 years were enrolled in a crosssectional study conducted across 4 tertiary hospitals in Cambodia. NP swabs were collected at hospital presentation. Depending on reported symptom constellations, sera was also taken in a subset of subjects for comparison of mNGS results. RNA was isolated from biosamples, converted to cDNA libraries, and sequenced on a NextSeq2000 (Illumina). Raw sequence reads were stripped for host reads and aligned to NCBI nucleotide and protein databases using a cloud-based bioinformatics platform (CZID). Results. NP swabs were collected from 97 subjects between April 2020 and June 2021. Subjects were predominantly male (53.6%) and young (median age 3 years [IQR 1-25]). Pathogens were identified in 42 (43.2%) NP swabs;of these, 26 (61.9%) were respiratory viruses including 9 rhinovirus, 7 coronavirus (1 SARS-CoV-2), and 5 respirovirus cases. Co-infection was identified in 3 subjects with coronavirus and respirovirus (N=2) and coronavirus and rhinovirus (N=1). Of subjects with paired sera and NP samples (N=61), 18 (29.5%) had positive NP swabs but negative sera, 7 (11.5%) had negative NP swabs but positive sera, 12 (19.7%) had positive NP swabs and sera, and 24 (39.3%) had negative NP swabs and sera. Pathogen hits correlated in NP swabs and sera in 10 of 12 subjects, including six subjects with chikungunya. Conclusion. mNGS can be successfully implemented in low-resource settings to identify emerging pathogens and common respiratory pathogens, including coinfecting pathogens, from NP swabs of febrile patients. mNGS may also be able to detect chikungunya from NP swab alone, raising the possibility of non-invasive diagnostics for infections associated with high viremic states.

Additional considerations for assessing COVID-19 impact on dengue transmission

This article reported an astounding drop in dengue risk in 2020 attributable to public health and social measures during the pandemic. Taking population immunity into account, this study acknowledged how the unprecedented dengue burden of 2019 might have driven high immunity to dengue in 2020. This study also mentioned idiosyncrasies in the model that could not be explained. Moreover, it also adds possible considerations of (1) administrative delays and (2) genotype-replacement events driving the 2019 epidemics affecting conclusions drawn from the model. Therefore, the greatest dengue year on record in 2019, in terms of incidence, be treated as unique in that it was probably fuelled by viral evolutionary events resulting in genotype replacements and might falsely augment the differential dengue virus burden between a higher-than-usual 6-year mean dengue incidence (inclusive of 2019) versus the comparison year of 2020. From an academic standpoint, this study would be curious to see how the model would perform if the outlier year of 2019 were removed.

Enabling participation in children and young people (CYP) with acquired brain injuries (ABI) and their families-mixed methods study-preliminary survey results

Introduction: Annually an estimated 40,000 CYP in the UK sustain an ABI with many experiencing significant, life-long impairments that impact on physical and psychological development, health-related quality of life (HRQoL), educational achievement and social inclusion. Patients and methods: A quantitative cross-sectional survey was completed as part of a mixed methods study which aims to explore the longer term needs of CYP-ABI aged 5-18 and their families in one region of the UK. Participants were recruited using eligibility criteria through a regional specialist clinical service. Ethical approval was gained (REC-20/ EM/0258). The survey consisted of demographic questions and standardised outcome measures completed by the parent or CYP-Pediatric Quality of Life Inventory 4.0 (PedsQL), PedsQL-Family Impact Module (PedsQL-FIM), Child and Adolescent Scale of Participation (CASP), Parental Health Questionnaire-4 (PHQ-4). Additional free text questions were included to capture parent and CYP goals, impact of Covid-19 lockdowns and any other information they wished to share. Results: 44 families have completed the survey so far, a response rate of 26%. CYP PedsQL scores indicated 31% were at risk of impaired HRQoL and the CASP indicated 68% had severely impaired social participation. 48% of families had impaired family HRQoL (PedsQL-FIM) and 48% of parents screened positive for anxiety, depression or both (PHQ-4). Conclusion: These preliminary results indicate the long-term impact of an ABI on CYP and family HRQoL and CYP social participation. The context behind these scores will be explored more deeply in qualitative interviews during the next phase of the study.

SETTING UP A GERIATRIC LIAISON SERVICE WITHIN UROLOGY IN A DISTRICT GENERAL HOSPITAL

Introduction One might refer to urologists as the ‘hidden providers’ of geriatric care, ultimately sought out by many geriatric patients. POPS, the Peri-Operative care of Older People’s Service started at Guys Hospital in London is often quoted as the gold standard for liaison services. Having set up liaison services in Orthopaedics and General Surgery in my previous job, an exciting opportunity arose after the first COVID—19 wave when I found my new office directly under the Urology Assessment Unit. Method A Geriatric Urology liaison service was set up by a Consultant Geriatrician with SpR support. One hour per week was agreed within the department to pilot the service. By May 2021 the service had been running for 8 months. During this period 30 patients had been seen (36 patient visits). Results The patient’s mean age was 82 years. The advice given included: O Stopping medication (7 cases) O Recommending iron infusions instead of tablets (5 cases) O Adjusting analgesia (4 cases) O Ordering brain imaging (3 cases) Commonly there was the recognition of the need for palliative care in this frail population. There have been complex cases: O A gentleman with a large perinephric bleed. O A young man with seizures and cognitive issues following renal stones. O A patient with post-operative rhabdomyolysis following nephrectomy. Pre-operative assessments have now been started as part of enhanced care: O Two cystectomy patients (one ward/one telephone) O Two TURBT patients (one with low sodium). Conclusion Staff feedback has been excellent especially linking to the Palliative Care Team. We presented our data at the Urology governance meeting in September 2021 and again received excellent feedback. The urology staff have felt increasingly supported. Data collection has helped build a business case for two Consultant posts in surgical liaison.

Digit ratios and their asymmetries as risk factors of developmental instability and hospitalization for COVID-19.

COVID-19 presents with mild symptoms in the majority of patients but in a minority it progresses to acute illness and hospitalization. Here we consider whether markers for prenatal sex hormones and postnatal stressors on developmental instability, i.e. digit ratios and their directional and unsigned asymmetries, are predictive of hospitalization. We focus on six ratios: 2D:3D; 2D:4D; 2D:5D; 3D:4D; 3D:5D; 4D:5D and compare hospitalized patient and control means for right, and left ratios, directional asymmetries (right-left) and unsigned asymmetries [|(right-left)|]. There were 54 patients and 100 controls. We found (i) patients differed in their digit ratios from controls (patients > controls) in all three ratios that included 5D (2D:5D, 3D:5D and 4D:5D) with small to medium effect sizes (d = 0.3 to 0.64), (ii) they did not differ in their directional asymmetries, and (iii) patients had greater |(right-left)| asymmetry than controls for 2D:4D (d = .74) , and all ratios that included 5D; 2D:5D (d = 0.66), 3D:5D (d = .79), 4D:5D (d = 0.47). The Composite Asymmetry of the two largest effects (2D:4D + 3D:5D) gave a patient and control difference with effect size d = 1.04. All patient versus control differences were independent of sex. We conclude that digit ratio patterns differ between patients and controls and this was most evident in ratios that included 5D. Large |(right-left)| asymmetries in the patients are likely to be a marker for postnatal stressors resulting in developmental perturbations and for potential severity of COVID-19.