Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad ...clinical effects of varying iron status.
Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene HFE and rs855791 in the transmembrane protease serine 6 gene TMPRSS6) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio OR scaled to a standard deviation SD increase in genetically determined serum iron levels 0.72, 95% confidence interval CI 0.64-0.81, P = 4 × 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 × 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 × 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.
Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.
Abstract
The emergence of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has required an unprecedented response to control the spread of the infection and protect the most ...vulnerable within society. Whilst the pandemic has focused society on the threat of emerging infections and hand hygiene, certain infection control and antimicrobial stewardship policies may have to be relaxed. It is unclear whether the unintended consequences of these changes will have a net-positive or -negative impact on rates of antimicrobial resistance. Whilst the urgent focus must be on controlling this pandemic, sustained efforts to address the longer-term global threat of antimicrobial resistance should not be overlooked.
To investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective ...observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).
A retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.
A total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.
We found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.
To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection.
MEDLINE, EMBASE, and Web of Science were searched using broad-based ...search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed.
1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.
Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.
Microplastics (MPs, particles <5 mm) represent an emerging global environmental concern, having been detected in multiple aquatic species. However, very little is known about the presence of MPs in ...higher trophic level species, including cetaceans. We worked with community based monitors and Inuvialuit hunters from Tuktoyaktuk (Northwest Territories, Canada) to sample seven beluga whales (Delphinapterus leucas) in 2017 and 2018. Microplastics were detected in the gastrointestinal tracts in every whale. We estimate that each whale contained 18 to 147 MPs in their GI tract (average of 97 ± 42 per individual). FTIR-spectroscopy revealed over eight plastic polymer types, with nearly half being polyester. Fibres made up 49% of MPs. The diversity of MP shapes and polymeric identities in beluga points to a complex source scenario, and ultimately raises questions regarding the significance and long-term exposure of this pollutant in this ecologically and culturally valuable species.
•Microplastic particles (MPs) were found in all seven belugas harvested by Inuvialuit hunters.•Both fibres and fragments were found within stomachs and intestines, with all particles being <5 mm in size.•Nearly half of particles found were identified as PET (Polyethylene terephthalate).•Exposure pathways and health implications remain unclear.
A spherical harmonic model of the magnetic field of Jupiter is obtained from vector magnetic field observations acquired by the Juno spacecraft during its first nine polar orbits about the planet. ...Observations acquired during eight of these orbits provide the first truly global coverage of Jupiter's magnetic field with a coarse longitudinal separation of ~45 deg between perijoves. The magnetic field is represented with a degree 20 spherical harmonic model for the planetary ("internal") field, combined with a simple model of the magnetodisc for the field ("external") due to distributed magnetospheric currents. Partial solution of the underdetermined inverse problem using generalized inverse techniques yields a model ("Juno Reference Model through Perijove 9") of the planetary magnetic field with spherical harmonic coefficients well determined through degree and order 10, providing the first detailed view of a planetary dynamo beyond Earth.
Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in ...monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre.
In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak.
Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34–45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes.
Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing.
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