Next-Generation Sequencing and Influenza Virus: A Short Review of the Published Implementation Attempts

Influenza virus represents a major public health concern worldwide after recent pandemics. To aid the understanding and characterization of the virus in ever-increasing sample numbers, new research techniques have been used, such as next-generation sequencing(NGS). The current article review used Ovid MEDLINE and PubMed databases to conduct keyword searches and investigate the extent to which published NGS high-throughput approaches have been implemented to influenza virus research in the last 5 years, during which the increase in research funding for influenza studies has been coincidental with a significant per-base cost reduction of sequencing. Through the current literature review, it is evident that over the last 5 years, NGS techniques have been indeed applied to biological and clinical samples at increasing rates following a wide variety of approaches. The rate of adoption is slower than anticipated by most published studies, with three obstacles identified consistently by authors. These are the lack of suitable downstream analytical capacity, the absence of established quality control comparators, and the higher cost to comparable existing techniques

Digital public health leadership in the global fight for health security

The COVID-19 pandemic highlighted the need to prioritise mature digital health and data governance at both national and supranational levels to guarantee future health security. The Riyadh Declaration on Digital Health was a call to action to create the infrastructure needed to share effective digital health evidence-based practices and high-quality, real-time data locally and globally to provide actionable information to more health systems and countries. The declaration proposed nine key recommendations for data and digital health that need to be adopted by the global health community to address future pandemics and health threats. Here, we expand on each recommendation and provide an evidence-based roadmap for their implementation. This policy document serves as a resource and toolkit that all stakeholders in digital health and disaster preparedness can follow to develop digital infrastructure and protocols in readiness for future health threats through robust digital public health leadership.Peer reviewe

Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness

The Use of Digital Technology for COVID-19 Detection and Response Management in Indonesia: Mixed Methods Study

BACKGROUND: The COVID-19 pandemic has triggered the greater use of digital technologies as part of the healthcare response in many countries, including in Indonesia. OBJECTIVE: The objective of our study was to identify and review the use of digital health technologies in COVID-19 detection and response management in Indonesia. It is the world's fourth most populous nation, and Southeast Asia's most populous country, with considerable public health pressures. METHODS: This paper conducted a literature review of publicly accessible information in technical and scientific journals, as well as news articles between September 2020 to August 2022 to identify the use case examples of digital technologies in COVID-19 detection and response management in Indonesia. RESULTS: The results are presented into three groups, namely (i) Big Data, Artificial Intelligence and Machine Learning (technologies for the collection and/or processing of data); (ii) Healthcare System Technologies (acting at the public health level); and (iii) Population Treatment (acting at the individual patient level). Some of these technologies are the result of government-academia-private sector collaborations during the pandemic, which represent a novel, multi-sectoral practice in Indonesia within the public healthcare ecosystem. A small number of the identified technologies pre-existed the pandemic, but were upgraded and adapted for the current needs. CONCLUSIONS: Digital technologies were developed in Indonesia during the pandemic, with a direct impact in supporting the COVID-19 management, detection, response, and treatment. They addressed different areas of the technological spectrum, and with different levels of adoption, ranging from local, regional to national. The indirect impact from this wave of technological creation and use, is to provide a strong foundation for fostering future multi-sectoral collaboration within the national healthcare system of Indonesia

Building on health security capacities in Indonesia: Lessons learned from the COVID-19 pandemic responses and challenges

As an active member country of the WHO's International Health Regulation and Global Health Security Agenda, Indonesia, the world's fourth-most populous and largest archipelagic country has recorded the second-highest COVID-19 cases in Asia with over 1.8 million cases in early June 2021. This geographically and socially diverse country has a dynamic national and sub-national government coordination with decentralized authorities that can complicate a pandemic response which often requires nationally harmonized policies, adaptability to sub-national contexts and global interconnectedness. This paper analyses and reviews COVID-19 public data, regulations, guidance documents, statements and other related official documents to present a narrative that summarizes the government's COVID-19 response strategies. It further analyses the challenges and achievements of the country's zoonotic diseases preparedness and responses and lastly provides relevant recommendations. Findings are presented in four sections according to the Global Health Security Agenda capacities, namely epidemiological surveillance (detect capacity); laboratory diagnostic testing (respond capacity); data management and analysis (enable capacity); and the role of sub-national governments. The COVID-19 pandemic has been a catalyst for the rapid transformation of existing surveillance systems, inter-related stakeholder coordination and agile development from the pre-pandemic health security capacities. This paper offers several recommendations on surveillance, laboratory capacity and data management, which might be useful for Indonesia and other countries with similar characteristics beyond the COVID-19 response, such as achieving long-term health security, zoonoses and pandemic prevention, as well as a digital transformation of their governmental capacities

PTSD as an Endothelial Disease: Insights From COVID-19

SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and medial prefrontal cortex, increasing the vulnerability to stress related disorders. This is supported by observing the beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in both posttraumatic stress disorder and SARS-CoV-2 critical illness. In this narrative review, we take a closer look at the virus-host dialog and its impact on the renin-angiotensin system, mitochondrial fitness, and brain-derived neurotrophic factor. We discuss the role of furin cleaving site, the fibrinolytic system, and Sigma-1 receptor in the pathogenesis of psychological trauma. In other words, learning from the virus, clarify the molecular underpinnings of stress related disorders, and design better therapies for these conditions. In this context, we emphasize new potential treatments, including furin and bromodomains inhibitors

An interactive data visualisation application to investigate nosocomial transmission of infections

Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights. We describe a novel, open-source, application for visualising these data, and demonstrate its utility for investigating nosocomial transmission using a case study of a large outbreak of norovirus infection. Methods: We developed the application using Shiny, a web application framework for R. For the norovirus case study, cases were defined as patients who had a faecal sample collected at the hospital in a winter season that tested positive for norovirus. Patient demographics and ward admission dates were extracted from hospital systems. Detected norovirus strains were genotyped and further characterised through sequencing of the hypervariable P2 domain. The most commonly detected sub-strain was visualised using the interactive application. Results: There were 156 norovirus-positive specimens collected from 107 patients. The most commonly detected sub-strain affected 30 patients in five wards. We used the interactive application to produce three visualisations: a bar chart, a timeline, and a schematic ward plan highlighting plausible transmission links. Visualisations showed credible links between cases on the elderly care ward. Conclusions: Use of the interactive application provided insights into transmission in this large nosocomial outbreak of norovirus, highlighting where infection control practices worked well or could be improved. This is a flexible tool that could be used for investigation of any infection in any hospital by interactively changing parameters. Challenges include integration with hospital systems for extracting data. Prospective use of this application could inform better infection control in real time.</ns4:p

Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients.

Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Similar to previous pandemics, COVID-19 has been succeeded by well-documented postinfectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood– brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement