Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data.

Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity, which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic 'novel' lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1 % frequency, results were more reliable above a 5 % threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of error or bias in wastewater sequencing analysis and to appreciate the commonalities and differences across methods.

The Canadian VirusSeq Data Portal & Duotang: open resources for SARS-CoV-2 viral sequences and genomic epidemiology.

The COVID-19 pandemic led to a large global effort to sequence SARS-CoV-2 genomes from patient samples to track viral evolution and inform public health response. Millions of SARS-CoV-2 genome sequences have been deposited in global public repositories. The Canadian COVID-19 Genomics Network (CanCOGeN - VirusSeq), a consortium tasked with coordinating expanded sequencing of SARS-CoV-2 genomes across Canada early in the pandemic, created the Canadian VirusSeq Data Portal, with associated data pipelines and procedures, to support these efforts. The goal of VirusSeq was to allow open access to Canadian SARS-CoV-2 genomic sequences and enhanced, standardized contextual data that were unavailable in other repositories and that meet FAIR standards (Findable, Accessible, Interoperable and Reusable). In addition, the Portal data submission pipeline contains data quality checking procedures and appropriate acknowledgement of data generators that encourages collaboration. From inception to execution, the portal was developed with a conscientious focus on strong data governance principles and practices. Extensive efforts ensured a commitment to Canadian privacy laws, data security standards, and organizational processes. This Portal has been coupled with other resources like Viral AI and was further leveraged by the Coronavirus Variants Rapid Response Network (CoVaRR-Net) to produce a suite of continually updated analytical tools and notebooks. Here we highlight this Portal, including its contextual data not available elsewhere, and the 'Duotang', a web platform that presents key genomic epidemiology and modeling analyses on circulating and emerging SARS-CoV-2 variants in Canada. Duotang presents dynamic changes in variant composition of SARS-CoV-2 in Canada and by province, estimates variant growth, and displays complementary interactive visualizations, with a text overview of the current situation. The VirusSeq Data Portal and Duotang resources, alongside additional analyses and resources computed from the Portal (COVID-MVP, CoVizu), are all open-source and freely available. Together, they provide an updated picture of SARS-CoV-2 evolution to spur scientific discussions, inform public discourse, and support communication with and within public health authorities. They also serve as a framework for other jurisdictions interested in open, collaborative sequence data sharing and analyses.

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

BACKGROUND: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. METHODS: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. FINDINGS: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p<0.001). Preoperative chronic kidney disease (HR 6.5 (95% CI: 3.0 to 14.0) p≤0.001)), coronary artery disease (HR 3.3 (95% CI: 1.3 to 8.4) p=0.012) and pulmonary artery systolic pressure>50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. INTERPRETATION: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.

Bacteriophages playing nice: Lysogenic bacteriophage replication stable in the human gut microbiota.

Bacteriophages, viruses specific to bacteria, coexist with their bacterial hosts with limited diversity fluctuations in the guts of healthy individuals where they replicate mostly via lysogenic replication. This favors 'piggy-back-the-winner' over 'kill-the-winner' dynamics which are driven by lytic bacteriophage replication. Revisiting the deep-viral sequencing data of a healthy individual sampled over 2.4 years, we explore how these dynamics occur. Prophages found in assembled bacterial metagenomes were also found extra-cellularly, as induced phage particles (iPPs), likely derived from prophage activation. These iPPs were diverse and continually present in low abundance, relative to the highly abundant but less diverse lytic phage population. The continuous detection of low levels of iPPs suggests that spontaneous induction regularly occurs in this healthy individual, possibly allowing prophages to maintain their ability to replicate and avoiding degradation and loss from the gut microbiota.

Correction: Sutcliffe et al. Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut. Viruses 2021, 13, 455.

In the original publication [...].

Common Oral Medications Lead to Prophage Induction in Bacterial Isolates from the Human Gut.

Many bacteria carry bacteriophages (bacterial viruses) integrated in their genomes in the form of prophages, which replicate passively alongside their bacterial host. Environmental conditions can lead to prophage induction; the switching from prophage replication to lytic replication, that results in new bacteriophage progeny and the lysis of the bacterial host. Despite their abundance in the gut, little is known about what could be inducing these prophages. We show that several medications, at concentrations predicted in the gut, lead to prophage induction of bacterial isolates from the human gut. We tested five medication classes (non-steroidal anti-inflammatory, chemotherapy, mild analgesic, cardiac, and antibiotic) for antimicrobial activity against eight prophage-carrying human gut bacterial representative isolates in vitro. Seven out of eight bacteria showed signs of growth inhibition in response to at least one medication. All medications led to growth inhibition of at least one bacterial isolate. Prophage induction was confirmed in half of the treatments showing antimicrobial activity. Unlike antibiotics, host-targeted medications led to a species-specific induction of Clostridium beijerinckii, Bacteroides caccae, and to a lesser extent Bacteroides eggerthii. These results show how common medication consumption can lead to phage-mediated effects, which in turn would alter the human gut microbiome through increased prophage induction.

Not Just a Passing Phage.

The viral fraction of the human gut microbiota, or virome, has been studied in a limited capacity. In this issue of Cell Host & Microbe, Shkoporov et al. (2019) perform a longitudinal study with database-independent clustering of bacteriophage genomes and de novo taxonomic classification, increasing our understanding of the virome.

Chest pain risk assessment in Indigenous and non-Indigenous Australians using HEART Score.

OBJECTIVE: The objectives of this study were to investigate factors that correlate to cardiac events within 30 days in Indigenous and non-Indigenous Australians who present to ED with chest pain and to describe the predictive ability of the HEART Score in these groups. METHODS: Patients who presented with chest pain between 1 January 2013 and 16 May 2013 in a university hospital were retrospectively enrolled in the study. HEART Scores were retrospectively assigned to participants. The study's end-point was Major Adverse Cardiac Events (MACE) within 30 days. RESULTS: Participants (678) were enrolled in the study, of which 148 were Indigenous Australian. Twenty-eight percent of Indigenous Australian participants and 19% of non-Indigenous Australian participants were diagnosed with MACE within 30 days. Within the Indigenous Australian participant cohort, 1.6% of those with HEART Scores 0-3, 29% of those with HEART Scores 4-6 and 96% of those with HEART Scores 7-10 were diagnosed with MACE within 30 days. Within the non-Indigenous Australian participant cohort, 0.58% of those with HEART Scores 0-3, 17% of those with HEART Scores 4-6 and 79% of those with HEART Scores 7-10 were diagnosed with MACE within 30 days. The negative predictive value of HEART Scores 0-3 for ruling out MACE within 30 days was 98% for Indigenous participants and 99% for non-Indigenous participants. CONCLUSION: The HEART Score is a reliable predictor of patient outcome in both Indigenous and non-Indigenous Australians. Modification of the HEART Score may not be required for use in the Indigenous Australian population who present to the ED with chest pain.

A case of nonischemic cardiomyopathy associated with autoimmune polyglandular syndrome type III.

OBJECTIVE: To report a case of nonischemic dilated cardiomyopathy associated with autoimmune polyglandular syndrome (APS) type III. METHODS: A review of our patient's medical records was undertaken, and her clinical history, investigations, and outcome are described. In addition, a literature review of nonischemic dilated cardiomyopathy occurring in association with autoimmune polyendocrinopathies was performed. RESULTS: APS is diagnosed once a patient has developed at least 2 organ specific autoimmune diseases. APS III involves a combination of autoimmune diabetes and Graves' disease without adrenal insufficiency. Autoimmune cardiomyopathies are not described as a feature of this condition; however, there are a few reported cases of patients with autoimmune polyendocrinopathies developing a nonischemic dilated cardiomyopathy. In this case, a 30-year-old female developed vitiligo, Graves' disease, and latent autoimmune diabetes of the adult (LADA) over a 5-year period before presenting with conscious ventricular tachycardia (VT). This evolved into acute severe biventricular failure within a few weeks, which failed to resolve after adequate treatment of her other autoimmune conditions. CONCLUSION: Although nonischemic cardiomyopathies have been associated with APS in a few published cases, this is the first case to our knowledge in a patient with APS III.

Acute ST-elevation myocardial infarction in a 24-year-old woman with atheromatous coronary artery disease.

We report the case of a 24-year-old Torres Strait Islander woman who presented to a rural hospital ED with chest pain suspicious for myocardial ischaemia and was found to have an anterior ST-elevation myocardial infarction. She was thrombolysed and transferred to a tertiary centre where subsequent angiography revealed atheromatous disease of the left anterior descending coronary artery. We believe this to be one of the youngest reported cases of myocardial infarction due to atheromatous coronary artery disease, and demonstrates important learning points regarding the demographics and risk factors of indigenous patients with chest pain.

Trends in heart failure mortality in England and Wales since 1950.

BACKGROUND: This study aims to analyse trends in heart failure mortality for England and Wales from 1950 to 2003. METHODS: A retrospective observational study was conducted using death certificate and population data from the Office for National Statistics. RESULTS: Unadjusted heart failure deaths rose by a factor of more than four between 1950 and 1974 and then fell by a quarter by 2003. When standardised for changes in the age, sex and size of the population, there was a tripling in mortality rate from 1950 to the mid-1970s and since then, a sustained decline in mortality rate of 50% by 2003. The unadjusted female heart failure death rate has been between 1.5-2 times that of males since the early 1970s, but this is much less marked when the differences in the age distribution and sizes of the male and female populations are taken into account. Heart failure mortality trends are similar to those of coronary heart disease (CHD), but the peak is about 10 years earlier, and the male/female ratios are reversed. There is a continuing rise in deaths from both heart failure and CHD in the very elderly (>85 years). CONCLUSION: Unlike hospital trends, deaths from heart failure in the community in England and Wales show a decline since the early 1970s, in spite of an ageing population. This may reflect genuine changes in heart failure incidence, or parallel changes in CHD.

Evaluation of a cardiac prevention and rehabilitation programme for all patients at first presentation with coronary artery disease.

BACKGROUND: A cardiac prevention and rehabilitation (CP&R) programme was established for patients following their first clinical episode of coronary heart disease and 1-year outcomes were evaluated against British targets for coronary prevention. METHODS: Patients were evaluated 1 year after participation and outcomes compared with patients in the same health district registered with a random half of general practitioners not eligible for the programme (internal reference group) and patients identified in other English centres which participated in the EUROASPIRE II survey (external reference group). RESULTS: Three hundred and eighteen patients (76% of 417 incident cases) attended for 1-year screening. Of those who participated in the programme 96/113 (85%) attended (Group 1); 152/194 (78%) attended from all those eligible for the programme (Group 2); 166/223 (74%) attended from those receiving usual care in the same health district (Group 3 - internal reference group). In the EUROASPIRE II survey (Group 4 - external reference group) 362/744 (58%) patients were screened. Current smoking at follow-up was Group 1, 8%, Group 2, 11%, Group 3, 13% and Group 4, 18%. Proportions with a BMI < 25 kg/m were 29%, 25%, 32%, 18%; BP < 140/90 mmHg 58%, 56%, 49%, 48%; total cholesterol < 5.0 mmol/l 60%, 54%, 43%, 46%; antiplatelet therapy 88%, 87%, 86%, 81%; beta-blocker therapy 48%, 46%, 46%, 44%; and lipid lowering therapy 56%, 51%, 36%, 69% respectively. CONCLUSIONS: A CP&R programme was associated with a majority of coronary patients, whether attending the programme or not, achieving the Joint British Society's recommended prevention targets within the same health district. Specifically, a higher proportion of programme patients reached the cholesterol target of <5.0 mmol/l compared with both usual care and other centres elsewhere. This was achieved by using more lipid lowering therapy compared with usual care in the same health district, but less than other centres outside the health district. The overall results for the whole health district show a higher standard of preventive care compared with contemporary EUROASPIRE II results from other health districts in England.