Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs).

Long versus short course anti-microbial therapy of uncomplicated Staphylococcus aureus bacteraemia: a systematic review.

Background: Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear.

Objectives: To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB.

Methods: The following are the methods used for this study.

Exploring young people's attitudes to HIV prevention medication (PrEP) in England: a qualitative study.

Introduction: Young people aged 18-24 years old are a key demographic target for eliminating HIV transmission globally. Pre-exposure prophylaxis (PrEP), a prevention medication, reduces HIV transmission. Despite good uptake by gay and bisexual men who have sex with men, hesitancy to use PrEP has been observed in other groups, such as young people and people from ethnic minority backgrounds.

Integration of High-Throughput Imaging and Multiparametric Metabolic Profiling Reveals a Mitochondrial Mechanism of Tenofovir Toxicity.

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic complications. The antiviral drug tenofovir disoproxil fumarate (TDF) is an archetypal nephrotoxin, inducing mitochondrial abnormalities and urinary solute wasting, for reasons that were previously unclear.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

Introduction: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use.

Objective: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria.

Methods: Systematic review and meta-analysis was performed using major databases up to May 5, 2021.

Skeletal muscle mitochondrial dysfunction in contemporary antiretroviral therapy: a single cell analysis.

Objective: To quantify mitochondrial function in skeletal muscle of people treated with contemporary antiretroviral therapy.

Design: Cross-sectional observational study.

Methods: Quantitative multiplex immunofluorescence was performed to determine mitochondrial mass and respiratory chain complex abundance in individual myofibres from tibialis anterior biopsies.

Renal mitochondrial toxicity: effects of thymidine analogues and tenofovir disoproxil fumarate in African people with HIV.

We investigated the contributions of thymidine analogue and tenofovir disoproxil fumarate (TDF) antiretroviral therapy on renal mitochondrial toxicity in Ghanaian people with HIV (PWH). Similar levels of renal biochemical and mitochondrial dysfunction were seen, and there was no increased risk in PWH who had sequenced from thymidine analogue to TDF. However, mild renal impairment was associated with mitochondrial DNA damage in TDF but not thymidine analogue-treated PWH.

Molecularly Imprinted Polymer Nanoparticles Enable Rapid, Reliable, and Robust Point-of-Care Thermal Detection of SARS-CoV-2.

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivity and utilize antibodies as receptors, which can only function in narrow temperature and pH ranges. Consequently, molecularly imprinted polymer nanoparticles (nanoMIPs) are synthetized with a fast (2 h) and scalable process using merely a tiny SARS-CoV-2 fragment (∼10 amino acids).

Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults.

BACKGROUND: Safe and effective oral treatments are needed to improve clinical outcomes for nonhospitalized patients with Covid-19. Molnupiravir is an orally administered, small-molecule ribonucleoside prodrug shown to inhibit replication of severe acute respiratory syndrome coronavirus 2 in vitro and in animal models. METHODS: MOVe-OUT is an ongoing, phase 2/3, randomized, placebo-controlled, double-blind study evaluating the safety, efficacy, and pharmacokinetics of molnupiravir in nonhospitalized adults.

Evaluation of procalcitonin-guided antimicrobial stewardship in patients admitted to hospital with COVID-19 pneumonia.

Background: Procalcitonin is a biomarker that may be able to identify patients with COVID-19 pneumonia who do not require antimicrobials for bacterial respiratory tract co-infections.

Objectives: To evaluate the safety and effectiveness of a procalcitonin-guided algorithm in rationalizing empirical antimicrobial prescriptions in non-critically ill patients with COVID-19 pneumonia.

Methods: Retrospective, single-site, cohort study in adults hospitalized with confirmed or suspected COVID-19 pneumonia and receiving empirical antimicrobials for potential bacterial respiratory tract co-infection.

The Isolation and Deep Sequencing of Mitochondrial DNA.

In recent years, next-generation sequencing (NGS) has become a powerful tool for studying both inherited and somatic heteroplasmic mitochondrial DNA (mtDNA) variation. NGS has proved particularly powerful when combined with single-cell isolation techniques, allowing the investigation of low-level heteroplasmic variants both between cells and within tissues. Nevertheless, there remain significant challenges, especially around the selective enrichment of mtDNA from total cellular DNA and the avoidance of nuclear pseudogenes.

SARS-CoV-2 Testing of 11,884 Healthcare Workers at an Acute NHS Hospital Trust in England: A Retrospective Analysis.

Healthcare workers (HCWs) are known to be at increased risk of infection with SARS-CoV-2, although whether these risks are equal across all roles is uncertain. Here we report a retrospective analysis of a large real-world dataset obtained from 10 March to 6 July 2020 in an NHS Foundation Trust in England with 17,126 employees. 3,338 HCWs underwent symptomatic PCR testing (14.

SARS-CoV-2 transmission during rugby league matches: do players become infected after participating with SARS-CoV-2 positive players?

Objectives: To examine the interactions between SARS-CoV-2 positive players and other players during rugby league matches and determine within-match SARS-CoV-2 transmission risk.

Methods: Four Super League matches in which SARS-CoV-2 positive players were subsequently found to have participated were analysed. Players were identified as increased-risk contacts, and player interactions and proximities were analysed by video footage and global positioning system (GPS) data.

COVID-19 Management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases Centre: A Retrospective Analysis.

Recent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is limited granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on management and outcome. We performed a retrospective single-centre analysis of clinical management and 28-day outcomes of consecutive adult inpatients with SARS-CoV-2 PCR-confirmed COVID-19 from 31 January to 16 April 2020 inclusive.

Prior SARS-CoV-2 infection is associated with protection against symptomatic reinfection.

• Whether SARS-CoV-2 infection confers immunity to reinfection is uncertain. • The ‘second wave’ of transmission offered an opportunity to examine this. • We observed no symptomatic reinfections in a cohort of healthcare workers.

Mitochondrial DNA Damage and Brain Aging in Human Immunodeficiency Virus.

Background: Neurocognitive impairment (NCI) remains common in people living with human immunodeficiency virus (PLWH), despite suppressive antiretroviral therapy (ART), but the reasons remain incompletely understood. Mitochondrial dysfunction is a hallmark of aging and of neurodegenerative diseases. We hypothesized that human immunodeficiency virus (HIV) or ART may lead to mitochondrial abnormalities in the brain, thus contributing to NCI.

Mitochondria and ageing with HIV.

Purpose Of Review: Some older people living with HIV (PLWH) exhibit features of unsuccessful ageing, such as frailty. Mitochondrial dysfunction is one of the best characterized ageing mechanisms. There has been recent interest in whether some people ageing with HIV may have an excess of mitochondrial dysfunction.

Current Challenges and Solutions in Research and Clinical Care of Older Persons Living with HIV: Findings Presented at the 9th International Workshop on HIV and Aging.

In the era of effective antiretroviral therapy, the number of older people with HIV (PWH) is increasing, and those aging with HIV are experiencing an increasing burden of age-associated comorbidities. Life expectancy among older PWH is approaching that of demographically comparable HIV-uninfected (HIV-) adults. With this changing demographic of PWH come new challenges for researchers and clinicians in how to identify, address, and manage the complex interplay of treated HIV infection and aging-associated factors.

Author Correction: Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos.

In the version of this Letter originally published, an author error led to the affiliations for Brendan Payne, Jonathan Coxhead and Gavin Hudson being incorrect. The correct affiliations are: Brendan Payne: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; this is a new affiliation 6 and subsequent existing affiliations have been renumbered.

Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos.

Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but how they arise is not clear. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Isolated PGCs have a profound reduction in mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules.