Development of a duplex real-time PCR assay for simultaneous detection and differentiation of Theileria equi and Babesia caballi.

Equine Piroplasmosis (EP) is a tick-borne disease caused by three apicomplexan protozoan parasites, Theileria equi (T. equi), Babesia caballi (B. caballi) and T. haneyi, which can cause similar clinical symptoms. There are five known 18S rRNA genotypes of T. equi group (including T. haneyi) and three of B. caballi. Real-time PCR methods for detecting EP based on 18S rRNA analysis have been developed, but these methods cannot detect all genotypes of EP in China, especially genotype A of T. equi. In this study, a duplex real-time PCR detection method was developed for the simultaneous detection and differentiation of T. equi and B. caballi. The primers and probes for this duplex real-time PCR assay were designed based on the conserved 18S rRNA gene sequences of all genotypes of T. equi and B. caballi including Chinese strain. Double-quenched probes were used in this method, which provide less background and more signal to decrease the number of false positives relative to single-quenched probes. The newly developed real-time PCR assays exhibited good specificity, sensitivity, repeatability and reproducibility. The real-time PCR assays were further validated by comparison with a nested PCR assay and a previous developed real-time PCR for EP and sequencing results in the analysis of 506 clinical samples collected from 2019 to 2020 in eleven provinces and regions of China. Based on clinical performance, the agreements between the duplex real-time PCR assay and the nPCR assay or the previous developed real-time PCR assay were 92.5% (T. equi) and 99.4% (B. caballi) or 87.4% (T. equi) and 97.2% (B. caballi). The detection results showed that the positivity rate of T. equi was 43.87% (222/506) (10 genotype A, 1 genotype B, 4 genotype C, 207 genotype E), while that of B. caballi was 5.10% (26/506) (26 genotype A), and the rate of T. equi and B. caballi co-infection was 2.40% (12/506). The established method could contribute to the accurate diagnosis, pathogenic surveillance and epidemiological investigation of T. equi and B. caballi infections in horses.

Perceptions, Barriers and Enablers on Salt Reduction in Malaysia Out of Home Sectors (MyOH): From Point of View of the Policy Makers and Food Industries (preprint)

Background: High salt intake is a major cause of hypertension and cardiovascular diseases. The out-of-home sectors have been identified as one of the contributors of high salt intake in the population. The National Salt Reduction Policy of Malaysia was initiated in 2015; however, out-of-home sectors are yet to be emphasized and perception by policy makers and the food industries towards salt reduction are yet unknown. This study aimed to determine the perceptions, barriers and enablers towards salt reduction in the out-of-home sector in Malaysia, as well as among the policy makers and the food industries. Methods: : This is a qualitative study via semi-structured in-depth interview (IDI) and focus group discussion (FGD) involving several stakeholders consisting of policy makers from five ministries, five non-government organizations (NGOs), food science/food technology researchers from five regions (West, North, East, South of Peninsular and East Malaysia/ Borneo) as well as the food industries. The IDI and FGD sessions were recorded, transcribed verbatim and analyzed thematically using Nvivo software version 12. Result: All participants agreed that salt intake in Malaysia is high and leads to hypertension and cardiovascular diseases. Lack of awareness, poor eating culture and behavior, and frequent eating out were among the causes of high salt intake. Awareness campaign and education, sodium content labelling and product reformulation were strategies that have been implemented by the government; whilst for the food industries, some of them have tried to reduce salt and labelled the sodium content on their food products. However, there were several barriers including perceived poor consumer acceptance, lack of knowledge and resources, challenges in reformulation, as well as unavailability of guidelines and salt targets. Hence, several enablers have been suggested, which include prioritizing salt reduction strategy, creating more awareness, collaboration and engagement, research and technology particularly for reformulation and shelf-life stability, incentives, and salt tax. Conclusion: Salt reduction efforts of out-of-home sector in Malaysia could be achieved through several measures or enablers that can overcome the barriers currently faced by the stakeholders, especially the policy makers, food industries and the consumers themselves. This study will benefit the policy makers to improve the salt reduction policy of out-of-home sectors and highlight the concerns among the food industries on the policy.

Remdesivir: A critical review (preprint)

Remdesivir has appeared to be the most effective medication against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is broadly administered to the coronavirus disease 2019 (COVID-19) patients around the world. Remdesivir is an RNA polymerase inhibitor with a broad spectrum of antiviral activities against RNA viruses in in-vitro and in-vivo models of SARS-CoV, the Middle East respiratory syndrome (MERS), and SARS-CoV-2. Remdesivir is the first Food and Drug Administration (FDA) approved anti-SARS-CoV-2 treatment for adult and pediatric patients and has been used intravenously for patients requiring hospitalization for COVID-19. However, questions have been raised about the value of remdesivir in treating COVID-19, and governing bodies worldwide have been hesitant to approve this medication. Nevertheless, in the context of the public health emergency and the urgent need for effective treatments for patients with COVID-19, remdesivir has been approved by several authorities worldwide. Here, we discuss the characteristics and applications of remdesivir, and various challenging studies with different outcomes about its efficacy are also reviewed.

From skirmishes to protracted battles: a bibliometric analysis about human beings and coronaviruses from 1991 to 2020 (preprint)

Background: The coronavirus disease 2019 pandemic (COVID-19) has caused an unprecedented upsurge in the publication of scientific studies as the global community has collaborated to control the spread of the disease. Methods: We conducted a bibliometric analysis to evaluate the research trends and identify the core content based on publication output, the geographic distribution, collaborations and keywords. We searched for articles published from 1900 to June 30, 2020 based on the Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) in the Web of Science. Results: Our analysis revealed the following: (1) The number of publications clearly increased after the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks and sharply increased during the COVID-19 outbreak. Compared with SARS and MERS, COVID-19 generated a more dramatic and prolonged upsurge in publication. (2) Compared with SARS and MERS, COVID-19 had a more widespread and powerful effect on countries and territories, with a rapid onset. Countries and territories engaged in more international collaboration and communication to cope with the epidemics, and the COVID-19 pandemic led to marked increases in research advancements. (3) Based on the keywords, we found that multiple methods were used to address the COVID-19 pandemic that were based on biology, especially the immune response. Conclusions: Epidemics lead to an extreme acceleration and changes in research.

Shapify: Pathways to SARS-CoV-2 Frameshifting Pseudoknot (preprint)

Background: Multiple viruses including HIV, MERS-CoV (coronavirus responsible for Middle East Respiratory Syndrome, MERS), SARS-CoV (coronavirus responsible for SARS) and SARS-CoV-2 (coronavirus responsible for COVID-19) use a mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to successfully replicate. SARS-CoV-2 possesses a unique RNA pseudoknotted structure that stimulates -1 PRF. Recent experiments identified small molecules as antiviral agents that can bind to the pseudoknot and disrupt its stimulation of -1 PRF. Targeting -1 PRF in SARS-CoV-2 to impair viral replication can improve patients' prognoses.Crucial to developing these successful therapies is modeling the structure of the SARS-CoV-2 -1 PRF pseudoknot.Our goal is to expand knowledge of possible pseudoknot conformations. Results: : Following a structural alignment approach, we identify similarities in -1 PRF pseudoknots of SARS-CoV-2, SARS-CoV, and MERS-CoV. We introduce Shapify , a novel algorithm that given an RNA sequence incorporates structural reactivity (SHAPE) data and partial structure information to output an RNA secondary structure prediction within a biologically sound hierarchical folding approach. Shapify helps us to better understand non-native SARS-CoV-2 -1 PRF pseudoknot conformations that are relevant to structure function and may correlate with -1 PRF efficiency. We provide in-depth analysis by investigating the structural landscape for the SARS-CoV-2 -1 PRF pseudoknot, including reference and mutated sequences. To better understand the impact of mutations, we provide insight on SARS-CoV-2 -1 PRF pseudoknot sequence mutations and their effect on the resulting structure. Conclusion: We identify the consensus structure for SARS-CoV, SARS-CoV-2, and MERS-CoV -1 PRF pseudoknots; this similarity in functional RNA structures aids treatment preparation for existing and emergent viruses. Shapify predictions are guided both by SHAPE data and partial structure information. Applied to the SARS-CoV-2 -1 PRF pseudoknot, Shapify unveiled previously unknown pathways from initial stems to pseudoknotted secondary structures. Where SHAPE data is unavailable we provide predictions for noteworthy SARS-CoV-2 -1 PRF mutated pseudoknot sequences. By contextualizing our work with available experimental data, our structure predictions motivate future RNA structure-function research and can aid 3-D modeling of pseudoknots.

Planepooling and Air Taxis for Post-COVID Aviation (preprint)

For most of its history, commercial aviation has tended toward large airplanes, large airports, and rigidly scheduled flights. Now, however, two phenomena—technological innovation and long-term societal changes accelerated by the COVID-19 pandemic—are creating an environment in which many flight routes would be better served by “planepooling”: smaller planes, smaller airports, and, for some routes, ad hoc scheduling. We highlight social and technological changes—including COVID-19 prevention measures, electrification of aircraft, and autonomous planes and air taxis—that could make private regional aviation attractive and affordable for business travelers and the middle class. Making planepooling convenient and cost-effective will require some technological advances and some changes in public policy. We propose in particular that regulators consider more-flexible Essential Air Service grants to small airports and the development of a market for regional aviation aerial corridors.

Psychological Impact of Covid-19 Pandemic: Lockdown Induced Anxiety and Its Impact on Sleep Quality in Adults Between 18-50 Years of Age (preprint)

BACKGROUND:- COVID 19 pandemic is the global health emergency and most critical health calamity of the century 4 .The COVID-19 belongs to the family of virus that causes illness such as common cold to severe infection causing Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory distress syndrome (SARS)CoV1. RESULTS:- 30 questions were asked combining of 5 components of which 4 were demographic questions and 1 willingness to participate. Total 196 subjects were chosen randomly between the age group of 18 years to 50 years from all over the Maharashtra. The subjects were both male and female. CONCLUSION :- In Our study the total sample size was 196. Population was significantly affected in all the components. Out of 196, 49% population was affected in sleep quality, and 57 % population was affected in anxiety.

Could docosahexaenoic acid (DHA), found in breast milk and artificial baby milks, protect infants and children from COVID-19 and make them less susceptible to COVID-19-related severe illness, as well as treat adult COVID-19 patients in combination with retinoic acid? A plan for observation and intervention (preprint)

SARS-CoV-2, which causes COVID-19, is a new virus that has spread fast over the world. The severity of COVID-19 at different ages has been a notable and constant observation: severity, the requirement for hospitalization, and mortality all grow sharply with age, although severe disease and death are uncommon in children and young adults.. The majority of children infected with SARS-CoV-2 are asymptomatic or have moderate symptoms, which include fever, cough, pharyngitis, gastrointestinal symptoms, and changes in taste and smell. The question of whether children are less likely to be infected with SARS-CoV-2 is still being debated. Children make up only 1 to 2% of all SARS-CoV-2 cases, according to large epidemiological research. these numbers are heavily, depend on testing criteria, and in many reports, testing was limited to those who were symptomatic or required hospitalization, which is less common in children.. According to certain research, children are just as likely as adults to contract SARS-CoV-2.9. Recent research suggests that children are less likely to become infected after coming into touch with a SARS-CoV-2-positive person.According to some reports, children and adolescents have similar virus loads and are hence just as likely to transmit SARS-CoV-2 as adults. Furthermore, the viral load in asymptomatic and symptomatic people may be identical. Reassuringly, transmission of the virus from children to other children or adults in schools has been infrequent.Children are less likely to be infected with SARS-CoV-2 and have less severe symptoms, which is similar to what has been observed with SARS-CoV-1 and Middle East respiratory disease (MERS)-CoV. Infection with most other respiratory viruses (e.g., respiratory syncytial virus (RSV), metapneumovirus, parainfluenza, or influenza viruses), on the other hand, has a far higher prevalence and severity in youngsters. Dr. Mahmoud Elkazzaz and Dr Amr kamel khalil Ahmed, the lead investigators of this observational study, recently published a preprint that demonstrated Docosahexaenoic acid (DHA) had a high binding affinity and greatest interactions with ACE2 active sites, as well as a moderate binding affinity and moderate interactions with the active sites of IL-6. The Docosahexaenoic acid (DHA) interacts with different active sites of IL6 and ACE2 which are involved in direct or indirect contacts with the ACE2 and IL-6 receptors which might act as potential blockers of functional ACE2 and IL-6 receptor complex.. A study proposed, a clinical benefit of targeting IL-17A signaling and the synergic inflammatory cytokine IL-6 to manage COVID-19 patients, particularly those presenting with cytokine storm syndrome.Hypercytokinemia, caused by notably high pro-inflammatory cytokines such as interleukin (IL)-1B, IL-6, IL-8, and IL-17, is mostly linked to the worsened clinical presentation of COVID-19 patients(14). In PBMCs from individuals with relapsing-remitting multiple sclerosis, a combination of docosahexaenoic acid (DHA) and all-trans-retinoic acid (ATRA) inhibits IL-17 gene expression. Conclusions: Docosahexaenoic acid (DHA) was detected in abundance in breast milk and other algal sources milk supplement used for newborns and children's feeding. As a result, we believe that docosahexaenoic acid (DHA) may protect children and newborns thorough competing with COVID-19 for ACE2 receptors and inhibiting IL-6 activity and may possibly help them avoid a cytokine storm and save their lives through inhibiting IL-6 and preventing SARS- CoV-2 RBD attachment to ACE2. In addition to IL-17 was fond to increase COVID-19 inflammatory complication in this case DHA combined with retinoic acid is expected to be effective in inhibiting IL-6 and IL-17.

Impact of COVID-19 on Sri Lanka Economy (preprint)

The 2019 novel coronavirus disease (“COVID-19”) was first identified in December 2019 in Wuhan, the capital of Hubei Province in China. Since then the outbreak has significantly expanded across borders, leading the World Health Organisation (“WHO”) to declare COVID-19 a pandemic on 11 March 2020. As the number of cases increase globally, the epicentre for the disease has been shifting from Wuhan region in China to Europe and most lately, the United States of America. According to the information provided by WHO, the mortality rate of COVID-19 is likely to be significantly lower than for Severe Acute Respiratory Syndrome (“SARS”) or Middle East Respiratory Syndrome (“MERS”) but higher than for seasonal flu. Why is it so dangerous? Studies show that the average number of new infections generated by a single infectious person could be more than double that of SARS and five times that of the seasonal flu. As the outbreak continues to spread, governments across the world have resorted to varying levels of public health measures, including movement restrictions, nationwide curfews, travel bans and border closures to tackle the pandemic. These measures are having a huge impact on people’s lives, families and communities whilst having significant consequences on national economies and global trade. The world countries are facing a crucial moment in their economies due to the COVID-19. We are able to observe that the COVID-19 which was considered a health issue at the outset, gradually developed into an economic crisis. Though nearly 99.7 million people are affected by this on a word wide scale, nearly 2.14 million people have lost their lives. When considering Sri Lankan experiences, 59,167 people have been infected the death rate has risen to 287 till 234 of January 2021. From the report of the “world Economic Outlook” published by the international monitory fund, we find that in October 2020. The world economy has dropped by 4.4%. When compared to 2019, the world's economic grown is 0.6% nearly 90 million people are facing a great challenge to reach the daily income level of $1.90. 44 Developed economics have recorded a 5.8% economic drop in 2020 though has targeted a 3.9% increase in 2021. On the other hand, developing countries have recorded a 3.3% economic drop in 2020 and aims at a 6% economic growth in 2021. In 2020, the world economy has experienced a slump situation. To overcome this slump economic crisis the word central banks’ governments have implemented many economic reforms. At the same time the central banks have been engaged in activities towards relaxing their Monitory policies. In this activity they are mostly following (non-traditional policies) unconventional policies. Central banks have reduced their interest rates. Governments with the particular view of reducing the stress faced by the affected businesses are helped by tax reforms. Though the COVID-19 has taken the world economy to an unstable position, yet the expectation of the COVID-19 vaccines have boosts up the morale of the economically affected countries.

A Network-Biology Led Computational Drug Repurposing Strategy to Prioritize Therapeutic Options for COVID-19 (preprint)

The alarming pandemic situation of novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection, high drug development cost and slow process of drug discovery have made repositioning of existing drugs for therapeutics a popular alternative. It involves the repurposing of existing safe compounds which results in low overall development costs and shorter development timeline. In the present study, a computational network-biology approach has been used for comparing three candidate drugs i.e. quercetin, N-acetyl cysteine (NAC), and 2-deoxy-glucose (2-DG) to be effectively repurposed against COVID-19. For this, the associations between these drugs and genes of Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) diseases were retrieved and a directed drug-gene-gene-disease interaction network was constructed. Further, to quantify the associations between a target gene and a disease gene, the shortest paths from the target gene to the disease genes were identified. A vector DV was calculated to represent the extent to which a disease gene was influenced by these drugs. Quercetin was quantified as the best among the three drugs, suited for repurposing with DV of -70.19, followed by NAC with DV of -39.99 and 2-DG with DV of -13.71. The drugs were also assessed for their safety and efficacy balance (in terms of therapeutic index) using network properties. It was found that quercetin was a forerunner than other two drugs.Funding Information: None to declare. Declaration of Interests: None to declare.

Goldilocks Government (preprint)

Those committed to addressing the political and moral crises of the day—voting rights, racial justice, climate change, economic inequality, and the lingering effects of the Covid pandemic—don’t know where to turn. Federal legislative and regulatory pathways are choked off by senators quick to filibuster and by judges eager to strike down agency rules and orders. State pathways, in turn, are compromised by limited capacity, collective action problems, externalities, and scant economies of scale.This Article prescribes a third pathway: interstate agreements and compacts. Such arrangements—largely unnecessary when Washington is not pathologically dysfunctional—have a long and venerable constitutional pedigree and provide a legally sound and politically expedient “just-right” solution. Grouping clusters of states along the Pacific Coast Highway, the Amtrak Corridor, and the Rust Belt, we proffer four major compacts as cornerstones of a Blue New Deal. Beyond detailing these four strategic interventions, this Article makes the affirmative, normative case for interstate agreements and compacts playing a regular and prominent role in twenty-first century American governance—a case that sounds in democratic theory, administrative law, and political economy.

When the virus goes viral: An impetus to revisit COVID-19 scientific outrage using Web of Science platform and a recount on the lineage of pandemics (preprint)

Pandemics are epidemics or disease outbreaks, which rampage across countries and continents. The ongoing corona virus disease 2019 (COVID-19) has been a full-fledged pandemic for over a year now. With the death count mounting above two million, COVID-19 has globally impacted the economy, society, public health and all spheres of human life. COVID-19 is the third type of coronavirus disease outbreak after Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. This review paper discusses the medical perspectives of COVID-19 along with a recount on the numerous pandemics that have wreaked havoc in the past. AIDS which is ongoing, and cholera, influenza and plague have been recurring pandemics and merciless killers. Even with tremendous advancement in medical science, new pathogens continue to cause uncontrollable infections and deaths worldwide. Research in the fields of medicine, health and social sciences, psychology and so on is soaring as the world battles with COVID-19. Additionally, scientometric analysis has been performed using the Web of Science platform, a global citation database, to project the impact of COVID-19 on research in terms of scientific publications. As of 04th April 2021, 98,020 scientific works have been published of which 28 % are from the USA. Medical and health sciences have been the major focus of research globally, as the world works tirelessly to develop the ‘right’ vaccine that will make COVID-19 a disease of the distant past.

Critically ill patients with diabetes and Middle East respiratory syndrome: A multi-center observational study (preprint)

Background: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS). Methods: : This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012- January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality. Results: : Of the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, p<0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). Conclusions: : Half of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.

The Current Understanding and Potential Therapeutic Options to Combat COVID-19 (preprint)

Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). The novel coronavirus (SARS-CoV-2 or COVID19) was identified in December 2019 in Wuhan city, Hubei province of China, which represents a new strain that affects human populations. Till date the pathogen has infected more than 30 million people across the globe and killed close to one million. Currently, no specific medication and/or cure are available for this contagion. However, governments and pharmaceutical companies are working against time to quickly find an effective drug to defeat the virus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options.

The Current Understanding and Potential Therapeutic Options to Combat COVID-19 (preprint)

Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). The novel coronavirus (SARS-CoV-2 or COVID19) was identified in December 2019 in Wuhan city, Hubei province of China, which represents a new strain that affects human populations. Till date the pathogen has infected more than 30 million people across the globe and killed close to one million. Currently, no specific medication and/or cure are available for this contagion. However, governments and pharmaceutical companies are working against time to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options.

Economic Burden of Viral Acute Respiratory Infections in Upper-Middle-Income Countries: Protocol For A Systematic Review (preprint)

Objective: To synthesize the available data on the economic burden of Coronavirus Diseases 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Influenza-Like Illness (ILI), Respiratory Syncytial Virus (RSV)-related Acute Respiratory Infection (ARI), and Parainfluenza Virus type III (PIV3)-related ARI in Upper-Middle-Income Countries (UMIC), highlighting its major causes and comparing direct costs among nations. Study design: Systematic review, following the recommendations proposed in the Cochrane Handbook, but with some adaptations from previous economic studies. Review question: Is there any economic cost of viral ARI in UMIC? Types of studies to be included: Partial economic evaluation, such as Cost-of-Illness (COI) studies and burden of illness/diseases, database analysis, observational reports (cross-sectional studies, and prospective and retrospective cohort), and economic modelling studies that discuss one of the viral ARI in UMIC. No year of publication filter or language limit will be applied. Search databases: MEDLINE, EMBASE, LILACS, CINAHL, EconLit, CRD Library, MedRxiv, and Research Square. Moreover, hand searches of the bibliographies of included studies and relevant reviews identified during the screening process will be undertaken to identify any additional relevant study for inclusion in our review. Synthesis of results: Qualitative analysis. We will focus on the overall economic burden of the diseases on health systems and population; total direct cost; the contribution of different cost components to the economic burden (e.g. pharmacological therapy, hospitalization); comparative assessments of costs analysis across geographical location and time horizon; and current research gaps. Moreover, we intend to identify, when presented, prevalence and incidence rates of each disease. PROSPERO registration number: CRD42020225757.

Amplicon and metagenomic analysis of MERS-CoV and the microbiome in patients with severe Middle East respiratory syndrome (MERS) (preprint)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a zoonotic infection that emerged in the Middle East in 2012. Symptoms range from mild to severe and include both respiratory and gastrointestinal illnesses. The virus is mainly present in camel populations with occasional spill overs into humans. The severity of infection in humans is influenced by numerous factors and similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underlying health complications can play a major role. Currently, MERS-CoV and SARS-CoV-2 are co-incident in the Middle East and a rapid way is required of sequencing MERS-CoV to derive genotype information for molecular epidemiology. Additionally, complicating factors in MERS-CoV infections are co-infections that require clinical management. The ability to rapidly characterise these infections would be advantageous. To rapidly sequence MERS-CoV, we developed an amplicon-based approach coupled to Oxford Nanopore long read length sequencing. The advantage of this approach is that insertions and deletions can be identified – which are the major drivers of genotype change in coronaviruses. This and a metagenomic approach were evaluated on clinical samples from patients with MERS. The data illustrated that whole genome or near whole genome information on MERS-CoV could be rapidly obtained. This approach provided data on both consensus genomes and the presence of minor variants including deletion mutants. Whereas, the metagenomic analysis provided information of the background microbiome.

Independent Dentists in the UK have less access to Occupational Health (preprint)

Objectives Respiratory illnesses like Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome and the current SARS-CoV-2 virus pandemic are transmitted by respiratory droplets. Certain dental procedures generate aerosols, one of the highest sources of transmission of droplet infections. During the current pandemic, dentists in the UK were initially restricted in their work and now have guidance from NHS England and the Chief Dental Officer for the full resumption of safe and effective routine dental care to patients. Lack of work, impact on income and working in the continual pandemic situation are likely to cause significant mental stress in dentists. Occupational health (OH) can have a vital role to help such dentists remain in work by advising strategies to cope with stress and offering timely evidence-based interventions and adjustments. The aim was to assess if the dentists in the UK had access to OH and whether access to the OH services helped. Methods A survey link was sent to 200 dentists in the UK after the peak of the current pandemic. Results 124 dentists responded to the survey. The response rate was 62%. 59% of the dentists in the survey did not have access to OH services in their workplace. Only 15% of dentists working in the independent sector had access to OH services compared to 78% working in the NHS or having NHS contracts. None of the dentists in the survey accessed OH services. Conclusions Access to OH services for the dentists needs improvement, particularly in the Independent sector in the UK. Article Summary Strengths and limitations of the study: Sample representative of the population studied. No observer subjectivity Precise results Inflexible design, no control group and lack of random sampling

COVID-19 Pandemic: Insights into Molecular Mechanisms Leading Sex-based Differences in Patient Outcomes (preprint)

Recent epidemiological studies analysing sex disaggregated patient data in COVID-19 across the world revealed a distinct sex bias in the disease morbidity as well as the mortality— both being higher for the men. Similar antecedents have been known for the previous viral infections, including from coronaviruses, such as severe acute respiratory syndrome (SARS) and middle-east respiratory syndrome (MERS). A sound understanding of the molecular mechanisms leading the biological sex bias in the survival outcomes of the patients in relation to COVID-19 will act as an essential requisite for developing a sex differentiated approach for therapeutic management of this disease. Recent studies which have explored molecular mechanism(s) behind sex-based differences in COVID-19 pathogenesis are scarce, however, existing evidence, for other viral infections, provides important clues in this regard. In attempt to consolidate the available knowledge on this issue, we performed a systematic review of the existing empirical knowledge and recent experimental studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The online literature sources including PubMed, Medline (EBSCO & Ovid), Google Scholar, Science Direct, Scopus, Bio Medical and Web of Science (WoS) were searched for the relevant data. Additionally, published literatures were also explored extensively. The time period taken to review the COVID-19 specific data was from December 1, 2019 to November 20, 2020. The qualitative analysis of the collected data unravelled multiple molecular mechanisms, such as sex-linkage of viral host cell entry receptor and immune genes, sex hormone and gut microbiome mediated immune-modulation, as the possible reasons for the sex-based differences in patient outcomes in COVID-19.

Prevalence of delirium, depression, anxiety, and post-traumatic stress disorder among COVID-19 patients: protocol for a living systematic review (preprint)

Background: Previous studies on the impact of corona virus disease 2019 (COVID-19) on the mental health of the patients has been limited by the lack of relevant data. With the rapid and sustained growth of the publications on COVID-19 research, we will perform a living systematic review (LSR) to provide comprehensive and continuously updated data to explore the prevalence of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) among COVID-19 patients. Methods: We will perform a comprehensive search of the following databases: Cochrane Library, PubMed, Web of Science, Embase, and Chinese Biomedicine Literature to identify relevant studies. We will include peer-reviewed cross-sectional studies published in English and Chinese. Two reviewers will independently assess the methodological quality of included studies using the Joanna Briggs Institute Prevalence Critical Appraisal tool and perform data extraction. In the absence of clinical heterogeneity, the prevalence estimates with a 95% confidence interval (CI) of delirium, depression, anxiety, and post-traumatic stress disorder (PTSD) will be calculated by using random-effects model to minimize the effect of between-study heterogeneity separately. The literature searches will be updated every three months. We will perform meta-analysis if any new eligible studies or data are obtained. We will resubmit an updated review when there were relevant changes in the results, i.e. when outcomes became statistically significant (or not statistically significant anymore) or when heterogeneity became substantial (or not substantial anymore). Discussion: This LSR will provide an in-depth and up-to-date summary of whether the common neuropsychiatric conditions observed in patients hospitalized for severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS) are also prevalent in a different stage of COVID-19 patients. Systematic review registration PROSPERO CRD42020196610