# bib

id: cord-016451-k8m2xz0e
title: Influenza, Measles, SARS, MERS, and Smallpox
author: Chertow, Daniel S.
date: 2020-01-03
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120728/
doi: 10.1007/978-3-030-33803-9_5
summary:
  Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. Measles infects and disrupts tissues throughout the body; however, severe disease is primarily due to lower respiratory tract and neurological complications [72] . Global epidemiology of avian influenza A H5N1 virus infection in humans, 1997-2015: a systematic review of individual case data Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection Viral RNA in blood as indicator of severe outcome in Middle East respiratory syndrome coronavirus infection Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection

abstract:
  Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. These biologically diverse viruses enter and replicate within host cells triggering viral- and host-mediated damage that results in pneumonia and multiorgan failure in severe cases. Early case identification and strict infection control limit healthcare transmission. Vaccination allowed smallpox eradication and limits global measles and seasonal influenza mortality. While SARS-coronavirus (CoV) is no longer circulating, MERS-CoV and zoonotic influenza viruses, with pandemic potential, remain persistent threats. Supportive critical care is the mainstay of treatment for severe disease due to these viral infections.


id: cord-017615-zjr6csla
title: Food Security in an Insecure Future
author: Hillman, John R.
date: 2016-11-25
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122219/
doi: 10.1007/978-3-319-48920-9_12
summary:
  Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. In a previous article , we considered definitions of food security in the modern era of rising global populations, discussing how food security might be attained in terms of security of water and fossil-fuel-derived energy supplies, climate change, rapid urbanisation, changing dietary trends, and modification of the natural environment leading to depleted natural resources, increasing environmental pollution, and the need to introduce modern technologies. Here, we consider potential adaptations to an insecure global future generally, and to the concerns in the Arab Middle East specifically, in the light of the economic realities of wide disparities in wealth, competition for resources, and widespread poverty in many parts of the globe, coupled to a relatively high population growth, on-going conflicts, attempted cultural genocides, potential conflicts, endemic corruption and nepotism, and epidemics of infectious diseases.

abstract:
  Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. Many Arab countries demonstrate nearly all the features of those countries classified as poor, less developed, or failing to achieve the eight Millennium Goals. Even the economies of the richer oil-exporting countries in the Region have been seriously damaged by the downturn in oil and gas prices as new sources come on stream elsewhere and demand falls as a result of renewable sources of energy becoming available.


id: cord-017731-xzfo5jjq
title: Foodborne Disease in the Middle East
author: Todd, Ewen C. D.
date: 2016-11-25
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122377/
doi: 10.1007/978-3-319-48920-9_17
summary:
  Food safety is a concern worldwide and according to the World Health Organization, developing countries are probably more at risk of foodborne illness because many of these, including those in the Middle East, have limited disease surveillance and prevention and control strategies. Like many other parts of the developing world, foodborne disease surveillance is limited and outbreaks are most often reported through the Press but with insufficient detail to determine the etiological agents and the factors contributing to the outbreaks, leading to speculation to the cause by those interested or responsible for food prevention and control. Thus, the main foodborne disease issues are with homemade, restaurant and street food, where isolated claims of illness are followed up by inspections and possible punitive action by public health agencies responsible for food safety.

abstract:
  Food safety is a concern worldwide and according to the World Health Organization, developing countries are probably more at risk of foodborne illness because many of these, including those in the Middle East, have limited disease surveillance and prevention and control strategies. Specifically, the Middle East and North Africa (MENA) region has the third highest estimated burden of foodborne diseases per population, after the African and South-East Asia regions. However, it is difficult to determine what the burden is since little is published in peer-reviewed journals or government reports for public access. This chapter reviews 16 autonomous nations, namely, Afghanistan, Bahrain, Egypt, Iran, Iraq, Israel, Palestine, Kuwait, Lebanon, Oman, Pakistan, Qatar, Saudi Arabia (KSA), Syrian Arab Republic (Syria), United Arab Emirates (UAE) and Yemen. Countries range in size from Bahrain with 1.8 million inhabitants to Pakistan with a population of 184 million. Agriculture and local food production is much influenced by water availability for irrigation. Water shortages are most severe in the Gulf countries which rely on aquifers, desalination, and recycled waste water for most of their water supplies. This means that most food is imported which is expensive if not subsidized through petrodollars. This impacts food security which is a particular concern in countries under conflict, particularly, Syria, Yemen and Iraq. Gastrointestinal infections are frequent in this region from Salmonella Typhi and other Salmonella spp., Shigella spp., Campylobacter jejuni and C. coli, rotavirus, hepatitis A virus, parasites, and more rarely from Aeromonas, Yersinia enterocolitica, Brucella spp., and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Reports indicate that children are the most susceptible and that many isolates are multidrug resistant. Chemical contamination of water supplies and crops are probably more of a concern than published reports indicate, because of widespread indiscriminate use of fertilizers, antibiotics, and pesticides, coupled with increased industrial pollution affecting the water supplies. Like many other parts of the developing world, foodborne disease surveillance is limited and outbreaks are most often reported through the Press but with insufficient detail to determine the etiological agents and the factors contributing to the outbreaks, leading to speculation to the cause by those interested or responsible for food prevention and control. However, there are some well investigated outbreaks in the region that have those details, and reveal where the shortcomings of both the establishments and the inspection systems have been. Where the causative agents are known, the kinds of pathogens are generally similar to those found in the West, e.g., Salmonella, but many outbreaks seem to have short incubation periods that point to a toxin of some kind of chemical or biological origin, but these are almost never identified. Because of sectarian warfare, residents and refugees have been given food that has made them sick and solders? have been deliberately poisoned. Research has been focused on microbial contamination of locally-sold foodstuffs and manager and employee knowledge of food safety and hygienic conditions in food preparation establishments. An innovative pilot project in Qatar is to use seawater and sunlight for raising crops through the Sahara Forest Project. All countries have some kind of food establishment inspection system, but they tend to be punitive if faults are found in management or employees on the premises rather than being used for their education for improving food safety. Restaurants may be closed down and owners and employees fined for often unspecified infringements. However, some food control agents are moving towards employee training through seminars and courses before problems occur, which is a good disease prevention strategy. Unfortunately, many of the food handlers are from Asian countries with languages other than Arabic and English, which makes effective food safety communication and training difficult. Tourists visiting popular resorts in Turkey and Egypt have suffered from foodborne illnesses, usually of unknown origin but poor hygienic conditions are blamed with law suits following, and the adverse publicity affects the long-term viability of some of these resorts. Food exports, important for local economies, have occasionally been contaminated resulting in recalls and sometimes illnesses and deaths, notably fenugreek seeds from Egypt (E. coli O104:H4), pomegranate arils from Turkey (hepatitis A virus), and tahini from Lebanon (Salmonella). Overall, in recent decades, the Middle East has made strides towards improving food safety for both residents and foreign visitors or ex-pat workers. However, within the countries there are large discrepancies in the extent of effective public health oversight including food safety and food security. Currently, almost all of the countries are involved to a greater or lesser extent in the civil wars in Syria and Yemen, or are affected through political tensions and strife in Egypt, Iraq, Iran, Israel, Palestine, Lebanon and Turkey. In addition, the current overproduction of oil on a world-wide scale has led to a rapid decrease in revenues to most Gulf states. All this points to a severe setback, and an uncertain foreseeable future for improvements in obtaining both sufficient and safe food for residents in this region.


id: cord-022046-q1exf47s
title: An Overview of Middle East Respiratory Syndrome in the Middle East
author: Toosy, Arshad Haroon
date: 2018-09-28
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152387/
doi: 10.1016/b978-0-323-55228-8.00042-4
abstract: nan
summary:
  Middle East respiratory syndrome (MERS) is an emerging infectious zoonotic disease caused by a novel coronavirus (CoV). 4 Surveillance of DCs in KSA has shown that MERS-CoV clade B has been enzootic in the camel population in Arabia Genetic deep sequencing methods (i.e., high-throughput sequencing) have been readily available to researchers since the disease was first reported. 8 Nevertheless, given the prevalence of MERS-CoV infection in the Middle East''s DC population and due to the potential for spillover to the human population in direct contact with DCs, the development of a vaccine for use in DCs may be feasible. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient


id: cord-022582-2e9i3m4b
title: Otolaryngologic Disorders
author: Potsic, William P.
date: 2012-03-21
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158348/
doi: 10.1016/b978-0-323-02842-4.50055-3
abstract: nan
summary:
  When fluid persists in the middle ear for 3 to 4 months, causing a hearing loss or is associated with ASOM, myringotomy and tympanostomy tube placement is helpful to resolve the hearing loss and reduce the frequency and severity of infection. In addition to antibiotics, treatment should include a wide field myringotomy from the anterior inferior quadrant to the posterior inferior quadrant, a tympanostomy tube placement for middle ear drainage, and a postauricular mastoidectomy to drain the subperiosteal abscess and the mastoid. These infections may be caused by a variety of viral and bacterial pathogens; and in addition to sore throat, symptoms include fever, mucopurulent nasal drainage, nasal obstruction, and facial pain. Symptoms typically appear at birth or soon thereafter and include inspiratory stridor, feeding difficulties, and, rarely, apnea or signs of severe airway obstruction. Children afflicted with recurrent respiratory papillomatosis present initially with hoarseness but may also have symptoms and signs of airway obstruction, including stridor.


id: cord-252222-wyamc46k
title: Middle East respiratory syndrome
author: Leung, Chi Hung Czarina
date: 2014-05-13
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url: https://www.ncbi.nlm.nih.gov/pubmed/24818865/
doi: 10.1007/s00134-014-3303-y
abstract: nan
summary:
  Middle East respiratory syndrome (MERS) is due to RNA betacoronavirus (MERS-CoV) infection. The apparent epidemiology may be biased by selective reporting of more severe cases and the small total number of patients makes it susceptible to distortion by individual outbreaks. Clinical suspicion, therefore, depends on vigilance and, for the present time, on a history of travel to the Middle East or contact with a patient with respiratory disease and an appropriate travel history [11] . Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk Emerging human Middle East respiratory syndrome coronavirus causes widespread infection and alveolar damage in human lungs Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study


id: cord-252883-1ub01j2x
title: Focus on Middle East respiratory syndrome coronavirus (MERS-CoV)
author: Bleibtreu, A.
date: 2019-11-11
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url: https://api.elsevier.com/content/article/pii/S0399077X19310546
doi: 10.1016/j.medmal.2019.10.004
summary:
  Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The first case of infection attributed to Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in Saudi Arabia in June 2012 [1] . Despite these viruses being identified in several reports as causing lower respiratory tract infections, it was generally accepted that coronaviruses were of low pathogenicity until the emergence of SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) in 2002, a virus with a fatality rate estimated at 10%. Very shortly afterwards, in September 2012, a second patient was admitted to hospital in the United Kingdom for severe respiratory infection related to a novel coronavirus following travel to the Middle East. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

abstract:
  Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.


id: cord-255488-nvgz53su
title: Development of a Mouse-Adapted MERS Coronavirus
author: Li, Kun
date: 2019-09-14
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url: https://doi.org/10.1007/978-1-0716-0211-9_13
doi: 10.1007/978-1-0716-0211-9_13
summary:
  An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. Alternative strategies for the creation of mouse models of MERS-CoV infection are generation of DPP4 humanized mice and adaptation of the virus to the animals. Similarly, our human DPP4 knock-in mouse model supported MERS-CoV replication but did not lead to a severe lung disease phenotype [33] . Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4 Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice

abstract:
  First identified in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that can cause acute respiratory distress syndrome (ARDS), multiorgan failure, and death, with a case fatality rate of ~35%. An animal model that supports MERS-CoV infection and causes severe lung disease is useful to study pathogenesis and evaluate therapies and vaccines. The murine dipeptidyl peptidase 4 (Dpp4) protein is not a functional receptor for MERS-CoV; thus, mice are resistant to MERS-CoV infection. We generated human DPP4 knock-in (hDPP4 KI) mice by replacing exons 10–12 at the mouse Dpp4 locus with exons 10–12 from the human DPP4 gene. The resultant human DPP4 KI mice are permissive to MERS-CoV (HCoV-EMC/2012 strain) infection but develop no disease. To generate a mouse model with associated morbidity and mortality from respiratory disease, we serially passaged HCoV-EMC/2012 strain in the lungs of young hDPP4 KI mice. After 30 in vivo passages, an adapted virus clone was isolated and designated MERS(MA)6.1.2. This virus clone produced significantly higher titers than the parental clone in the lungs of hDPP4 KI mice and caused diffuse lung injury and a fatal respiratory infection. In this chapter, we will describe in detail the procedures used to mouse adapt MERS-CoV by serial passage of the virus in lungs. We also describe the methods used to isolate virus clones and characterize virus infection.


id: cord-256784-wfaqim7d
title: MERS-CoV vaccine candidates in development: The current landscape
author: Modjarrad, Kayvon
date: 2016-06-03
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url: https://www.ncbi.nlm.nih.gov/pubmed/27083424/
doi: 10.1016/j.vaccine.2016.03.104
summary:
  Middle East Respiratory Syndrome (MERS-CoV) was first isolated in September 2012 from a patient in Saudi Arabia who presented two months earlier with severe acute respiratory infection and acute renal failure [1] . Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector-based vaccines carrying the spike protein of Middle East respiratory syndrome coronavirus Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in more than 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of MERS-CoV have created an urgent need for effective public health countermeasures, paramount of which is an effective means of prevention through a vaccine or antibody prophylaxis. Despite the relatively few number of cases to-date, research and development of MERS-CoV vaccine candidates is advancing quickly. This review surveys the landscape of these efforts across multiple groups in academia, government and industry.


id: cord-256806-g42n51n9
author: Khudhair, Ahmed
date: 2019-05-17
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url: https://www.ncbi.nlm.nih.gov/pubmed/31002068/
doi: 10.3201/eid2505.181728
summary:
  title: Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017 Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Our study aimed to identify risk factors for MERS-CoV seropositivity among live-animal market and slaughterhouse workers. The survey consisted of questions covering worker demographics; occupational history; contact with various animal species; travel history; medical history; consumption of raw camel milk, raw camel meat, and camel urine; specific tasks performed with camels; types of personal protective equipment (PPE) worn; and handwashing practices (Appendix 1, https://wwwnc.cdc.gov/EID/article/25/5/18-1728-App1.pdf). Our study investigated risk factors for MERS-CoV seropositivity in animal market and slaughterhouse workers at a site previously associated with zoonotic transmission of MERS-CoV. Among market workers, handling live camels and either administering medications to camels or cleaning equipment were practices associated with significantly increased risk for MERS-CoV seropositivity.

title:
  Risk Factors for MERS-CoV Seropositivity among Animal Market and Slaughterhouse Workers, Abu Dhabi, United Arab Emirates, 2014–2017

abstract:
  Camel contact is a recognized risk factor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Because specific camel exposures associated with MERS-CoV seropositivity are not fully understood, we investigated worker–camel interactions and MERS-CoV seroprevalence. We assessed worker seroprevalence in 2 slaughterhouses and 1 live-animal market in Abu Dhabi, United Arab Emirates, during 2014–2017 and administered an epidemiologic survey in 2016 and 2017. Across 3 sampling rounds during 2014–2017, we sampled 100–235 workers, and 6%–19% were seropositive for MERS-CoV at each sampling round. One (1.4%) of 70 seronegative workers tested at multiple rounds seroconverted. On multivariable analyses, working as a camel salesman, handling live camels or their waste, and having diabetes were associated with seropositivity among all workers, whereas handling live camels and either administering medications or cleaning equipment was associated with seropositivity among market workers. Characterization of high-risk exposures is critical for implementation of preventive measures.


id: cord-260518-mswb3q67
author: Zumla, Alimuddin
date: 2016-06-15
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url: https://www.sciencedirect.com/science/article/pii/S1201971216310967
doi: 10.1016/j.ijid.2016.06.012
summary:
  Since the Kingdom of Saudi Arabia is host to millions of pilgrims each year travelling from all continents, 29 tackling the threat of MERS and other infectious diseases with epidemic potential will require enhanced closer cooperation between those who provide human health, animal health, and environmental health services, locally, nationally, regionally, and internationally: the Middle Eastern, European, African, Asian, and American governments, veterinary groups, the WHO, the Food and Agriculture Organization (FAO), the African Union, the United Nations International Children''s Emergency Fund (UNICEF), The World Bank, Office International des Epizooties (OIE), CDC, Public Health England, the newly formed Africa CDC, and funding agencies among others. The persistence of MERS-CoV 4 years since its first discovery has created major opportunities for each of the Middle Eastern and African countries to take leadership of the ''One Health'' approach with a view to bringing this under regional and global umbrellas, to tackle new emerging and re-emerging infectious diseases with epidemic potential.

title:
  Taking forward a ‘One Health’ approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential

abstract:
  The appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. Over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included West Nile virus, Yellow fever virus, Ebola virus, Nipah virus, Lassa Fever virus, Hanta virus, Dengue fever virus, Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, severe acute respiratory syndrome coronavirus, highly pathogenic avian influenza viruses, Middle East Respiratory Syndrome Coronavirus, and Zika virus. The recent Ebola Virus Disease epidemic in West Africa and the ongoing Zika Virus outbreak in South America highlight the urgent need for local, regional and international public health systems to be be more coordinated and better prepared. The One Health concept focuses on the relationship and interconnectedness between Humans, Animals and the Environment, and recognizes that the health and wellbeing of humans is intimately connected to the health of animals and their environment (and vice versa). Critical to the establishment of a One Health platform is the creation of a multidisciplinary team with a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, vector biologists, viral phylogeneticists, and researchers to co-operate, collaborate to learn more about zoonotic spread between animals, humans and the environment and to monitor, respond to and prevent major outbreaks. We discuss the unique opportunities for Middle Eastern and African stakeholders to take leadership in building equitable and effective partnerships with all stakeholders involved in human and health systems to take forward a ‘One Health’ approach to control such zoonotic pathogens with epidemic potential.


id: cord-263016-28znb322
title: Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?
author: Omrani, A.S.
date: 2015-08-22
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url: https://www.ncbi.nlm.nih.gov/pubmed/26452615/
doi: 10.1016/j.jhin.2015.08.002
summary:
  Infection prevention/control and management guidelines for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection Infection prevention and control guidelines for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection Revised interim case definition for reporting to WHO e Middle East respiratory syndrome coronavirus (MERS-CoV) Revised interim case definition for reporting to WHO e Middle East respiratory syndrome coronavirus (MERS-CoV) Investigation of cases of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV); interim guidance updated 3 Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in

abstract:
  The Middle East Respiratory Coronavirus (MERS-CoV) was first isolated from a patient who died with severe pneumonia in June 2012. As of 19 June 2015, a total of 1,338 MERS-CoV infections have been notified to the World Health Organization (WHO). Clinical illness associated with MERS-CoV ranges from mild upper respiratory symptoms to rapidly progressive pneumonia and multi-organ failure. A significant proportion of patients present with non-respiratory symptoms such as headache, myalgia, vomiting and diarrhoea. A few potential therapeutic agents have been identified but none have been conclusively shown to be clinically effective. Human to human transmission is well documented, but the epidemic potential of MERS-CoV remains limited at present. Healthcare-associated clusters of MERS-CoV have been responsible for the majority of reported cases. The largest outbreaks have been driven by delayed diagnosis, overcrowding and poor infection control practices. However, chains of MERS-CoV transmission can be readily interrupted with implementation of appropriate control measures. As with any emerging infectious disease, guidelines for MERS-CoV case identification and surveillance evolved as new data became available. Sound clinical judgment is required to identify unusual presentations and trigger appropriate control precautions. Evidence from multiple sources implicates dromedary camels as natural hosts of MERS-CoV. Camel to human transmission has been demonstrated, but the exact mechanism of infection remains uncertain. The ubiquitously available social media have facilitated communication and networking amongst healthcare professionals and eventually proved to be important channels for presenting the public with factual material, timely updates and relevant advice.


id: cord-265380-2gs34xcw
author: Leist, Sarah R.
date: 2019-09-14
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url: https://www.ncbi.nlm.nih.gov/pubmed/31883094/
doi: 10.1007/978-1-0716-0211-9_12
summary:
  Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. utilized a unique approach for producing susceptible mice that could replicate human isolates of MERS-CoV in the lungs by infecting mouse lungs with an adenovirus that constitutively expresses the full-length hDPP4 gene ( Fig. 1) [37] . Attempts to restrict hDPP4 expression to epithelial cells of the lungs using constitutive tissue specific promoters (e.g., cytokeratin K18) yielded outcomes similar to those observed with SARS-CoV mouse models, wherein high levels of MERS-CoV infection/replication were detected in the brains (Fig. 1 ) [39] . Elevated human dipeptidyl peptidase 4 expression reduces the susceptibility of hDPP4 transgenic mice to Middle East respiratory syndrome coronavirus infection and disease

title:
  Genetically Engineering a Susceptible Mouse Model for MERS-CoV-Induced Acute Respiratory Distress Syndrome

abstract:
  Since 2012, monthly cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to cause severe respiratory disease that is fatal in ~35% of diagnosed individuals. The ongoing threat to global public health and the need for novel therapeutic countermeasures have driven the development of animal models that can reproducibly replicate the pathology associated with MERS-CoV in human infections. The inability of MERS-CoV to replicate in the respiratory tracts of mice, hamsters, and ferrets stymied initial attempts to generate small animal models. Identification of human dipeptidyl peptidase IV (hDPP4) as the receptor for MERS-CoV infection opened the door for genetic engineering of mice. Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. Here, we describe the generation of the 288–330(+/+) MERS-CoV mouse model in which mice were made susceptible to MERS-CoV by modifying two amino acids on mDPP4 (A288 and T330), and the use of adaptive evolution to generate novel MERS-CoV isolates that cause fatal respiratory disease. The 288–330(+/+) mice are currently being used to evaluate novel drug, antibody, and vaccine therapeutic countermeasures for MERS-CoV. The chapter starts with a historical perspective on the emergence of MERS-CoV and animal models evaluated for MERS-CoV pathogenesis, and then outlines the development of the 288–330(+/+) mouse model, assays for assessing a MERS-CoV pulmonary infection in a mouse model, and describes some of the challenges associated with using genetically engineered mice.


id: cord-265666-27ckjl7w
title: Working experiences of nurses during the Middle East respiratory syndrome outbreak
author: Kang, Hee Sun
date: 2018-05-30
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url: https://doi.org/10.1111/ijn.12664
doi: 10.1111/ijn.12664
summary:
  RESULTS: The following 4 major themes emerged: "experiencing burnout owing to the heavy workload," "relying on personal protective equipment for safety," "being busy with catching up with the new guidelines related to Middle East respiratory syndrome," and "caring for suspected or infected patients with caution." Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: An observational study

abstract:
  AIMS: To explore working experiences of nurses during Middle East respiratory syndrome outbreak. BACKGROUND: Since the first case of Middle East respiratory syndrome was reported on May 20, 2015 in South Korea, 186 people, including health care workers, were infected, and 36 died. DESIGN: A qualitative descriptive study. METHODS: Seven focus groups and 3 individual in‐depth interviews were conducted from August to December 2015. Content analysis was used. RESULTS: The following 4 major themes emerged: “experiencing burnout owing to the heavy workload,” “relying on personal protective equipment for safety,” “being busy with catching up with the new guidelines related to Middle East respiratory syndrome,” and “caring for suspected or infected patients with caution.” Participants experienced burnout because of the high volume of work and expressed safety concerns about being infected. Unclear and frequently changing guidelines were 1 of the common causes of confusion. Participants expressed that they need to be supported while caring for suspected or infected patients. CONCLUSION: This study showed that creating a supportive and safe work environment is essential by ensuring adequate nurse staffing, supplying best‐quality personal protective equipment, and improving communication to provide the quality of care during infection outbreak.


id: cord-266260-t02jngq0
title: A database of geopositioned Middle East Respiratory Syndrome Coronavirus occurrences
author: Ramshaw, Rebecca E.
date: 2019-12-13
txt: ./txt/cord-266260-t02jngq0.txt
cache: ./cache/cord-266260-t02jngq0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41597-019-0330-0
doi: 10.1038/s41597-019-0330-0
summary:
  As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged as a global health concern in 2012 when the first human case was documented in Saudi Arabia 1 . Previous literature reviews have looked at healthcare-associated outbreaks 9 , importation events resulting in secondary cases 10, 11 , occurrences among dromedary camels 12, 13 , or to summarize current knowledge and knowledge gaps of MERS-CoV 14, 15 . This database seeks fill gaps in literature and build upon existing notification data by enhancing the geographic resolution of MERS-CoV data and providing occurrences of both mammal and environmental detections in addition to human cases. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission

abstract:
  As a World Health Organization Research and Development Blueprint priority pathogen, there is a need to better understand the geographic distribution of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and its potential to infect mammals and humans. This database documents cases of MERS-CoV globally, with specific attention paid to zoonotic transmission. An initial literature search was conducted in PubMed, Web of Science, and Scopus; after screening articles according to the inclusion/exclusion criteria, a total of 208 sources were selected for extraction and geo-positioning. Each MERS-CoV occurrence was assigned one of the following classifications based upon published contextual information: index, unspecified, secondary, mammal, environmental, or imported. In total, this database is comprised of 861 unique geo-positioned MERS-CoV occurrences. The purpose of this article is to share a collated MERS-CoV database and extraction protocol that can be utilized in future mapping efforts for both MERS-CoV and other infectious diseases. More broadly, it may also provide useful data for the development of targeted MERS-CoV surveillance, which would prove invaluable in preventing future zoonotic spillover.


id: cord-267540-9p4rky4c
title: Middle east respiratory syndrome corona virus (MERS CoV): The next steps
author: Joseph, Iype
date: 2015-03-26
txt: ./txt/cord-267540-9p4rky4c.txt
cache: ./cache/cord-267540-9p4rky4c.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25811387/
doi: 10.1057/jphp.2015.9
summary:
  title: Middle east respiratory syndrome corona virus (MERS CoV): The next steps Developing countries are at risk of importing Middle East Respiratory Syndrome Corona Virus (MERS CoV) from the Middle East. To assess the disease transmission in these countries, supplemental surveillance strategies are urgently needed beyond the currently recommended measures. Saudi Arabia reported the first case of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) in September, 2012. Using the current strategy of virological testing of patients fulfilling the WHO case definition, India, Pakistan, Egypt, Bangladesh, Philippines, Sri Lanka, and Indonesia 13 (countries having sizable numbers of health workers employed in the Middle-East) have not yet detected more than one case each. When all care givers of a patient acutely ill with MERS CoV are immune, further transmission within the hospital is unlikely. Middle east respiratory syndrome coronavirus infections in health care workers

abstract:
  Developing countries are at risk of importing Middle East Respiratory Syndrome Corona Virus (MERS CoV) from the Middle East. Hospitals in the Middle East currently reporting the disease are staffed by immigrants. In the current hot spots for MERS CoV a sizeable portion of the population is from other countries, but many of these countries have yet to detect any importation of MERS CoV. To assess the disease transmission in these countries, supplemental surveillance strategies are urgently needed beyond the currently recommended measures. A few strategies to address the situation are: (i) improving preparedness with enhanced surveillance in particular regions; (ii) targeting certain sentinel groups for surveillance in hot spots; and (iii) limited use of serosurveillance. Recovered, immune patients can be employed to give patient care during outbreaks.


id: cord-269232-rhhmvnlp
title: First isolation of West Nile virus from a dromedary camel
author: Joseph, Sunitha
date: 2016-06-08
txt: ./txt/cord-269232-rhhmvnlp.txt
cache: ./cache/cord-269232-rhhmvnlp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27273223/
doi: 10.1038/emi.2016.53
summary:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. [6] [7] [8] [9] [10] [11] [12] [13] In this article, we report the first isolation of WNV from a dromedary calf in the United Arab Emirates during the process of MERS-CoV screening and the results of the comparative genome and phylogenetic analysis. 20 Notably, 14 amino-acid residues in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a (Figure 3) , with the majority of these differences observed in the putative E and NS5 proteins.

abstract:
  Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154–156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection.


id: cord-272513-umuiovrd
title: Variant analysis of SARS-CoV-2 genomes in the Middle East
author: Bindayna, Khalid Mubarak
date: 2020-10-09
txt: ./txt/cord-272513-umuiovrd.txt
cache: ./cache/cord-272513-umuiovrd.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.10.09.332692
doi: 10.1101/2020.10.09.332692
summary:
  We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. • Our hypothesis is that variants found in SARS-CoV-2 genomes from Middle Eastern samples will indicate delivery from Iran. • The aim is to explore the structure of Middle Eastern genome strains using multiple sequence alignment, tree generation and variant prediction (and others).

abstract:
  Background Coronavirus (COVID-19) was introduced into society in late 2019 and has now reached over 26 million cases and 850,000 deaths. The Middle East has a death toll of ∼50,000 and over 20,000 of these are in Iran, which has over 350,000 confirmed cases. We expect that Iranian cases caused outbreaks in the neighbouring countries and that variant mapping and phylogenetic analysis can be used to prove this. We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Findings We identified 2200 distinct genome variants including 129 downstream gene variants, 298 frame shift variants, 789 missense variants, 1 start lost, 13 start gained, 1 stop lost, 249 synonymous variants and 720 upstream gene variants. The most common, high impact variants were 10818delTinsG, 2772delCinsC, 14159delCinsC and 2789delAinsA. Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. Interpretation The phylogenetic and variant analysis provides unique insight into mutation types in genomes. Initial introduction of COVID-19 was most likely due to Iranian transmission. Some countries show evidence of novel mutations and unique strains. Increased time in small populations is likely to contribute to more unique genomes. This study provides more in depth analysis of the variants affecting in the region than any other study. Funding None


id: cord-275313-mfyff9ne
title: Treatment strategies for Middle East respiratory syndrome coronavirus
author: Modjarrad, Kayvon
date: 2016-01-01
txt: ./txt/cord-275313-mfyff9ne.txt
cache: ./cache/cord-275313-mfyff9ne.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26866060/
doi: nan
summary:
  Most recently, Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a novel cause of severe acute respiratory illness after first being identified in a Saudi Arabian patient in 2012 [2] . Much of the work to develop safe and effective MERS-CoV countermeasures has centred on vaccines, but the relatively low prevalence of the disease, the sporadic nature of the case clusters and the dearth of detailed knowledge on chains of transmission highlight the need for greater investments into the discovery of effective therapeutic and secondary prophylactic regimens for infected and exposed individuals. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol Towards the prophylactic and therapeutic use of human neutralizing monoclonal antibodies for Middle East respiratory syndrome coronavirus (MERS-CoV) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations.


id: cord-275602-cog4nma0
title: Emerging Infectious Diseases: a Review
author: Watkins, Kevin
date: 2018-06-22
txt: ./txt/cord-275602-cog4nma0.txt
cache: ./cache/cord-275602-cog4nma0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s40138-018-0162-9
doi: 10.1007/s40138-018-0162-9
summary:
  SUMMARY: In addition to the aforementioned pathogens, the Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah virus, New Delhi metallo-ß-lactamase-1 Enterobacteriaceae, Rift Valley Fever virus, and Crimean-Congo Hemorrhagic Fever virus are reviewed. In 1992, an expert committee that produced the Institute of Medicine report on emerging infections defined them as "new, reemerging, or drug-resistant infections whose incidence in humans has increased within the past two decades or whose incidence threatens to increase in the near future." Additionally, six major contributors to these diseases were presented and included changes in human demographics and behavior, advances in technology and changes in industry practices, economic development and changes in land-use patterns, dramatic increases in volume and speed of international travel and commerce, microbial adaptation and change, and breakdown of public health capacity [1] . The World Health Organization has prioritized a number of infectious diseases as requiring urgent need for research and development given the concern for potential of severe outbreaks.

abstract:
  PURPOSE OF REVIEW: This review highlights some of the recent concerning emerging infectious diseases, a number of them specifically that the World Health Organization has categorized as priorities for research. RECENT FINDINGS: Emerging and reemerging infectious diseases account for significant losses in not only human life, but also financially. There are a number of contributing factors, most commonly surrounding human behavior, that lead to disease emergence. Zoonoses are the most common type of infection, specifically from viral pathogens. The most recent emerging diseases in the USA are Emergomyces canadensis, the Heartland virus, and the Bourbon virus. SUMMARY: In addition to the aforementioned pathogens, the Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah virus, New Delhi metallo-ß-lactamase-1 Enterobacteriaceae, Rift Valley Fever virus, and Crimean-Congo Hemorrhagic Fever virus are reviewed. These pathogens are very concerning with a high risk for potential epidemic, ultimately causing both significant mortality and financial costs. Research should be focused on monitoring, prevention, and treatment of these diseases.


id: cord-278238-w1l8h8g8
title: Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches
author: Okba, Nisreen MA
date: 2017-04-13
txt: ./txt/cord-278238-w1l8h8g8.txt
cache: ./cache/cord-278238-w1l8h8g8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28412285/
doi: 10.1016/j.coviro.2017.03.007
summary:
  Nisreen MA Okba, V Stalin Raj and Bart L Haagmans Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The other candidate MVA-S, a viral-vector-based vaccine, induced systemic neutralizing antibodies and mucosal immunity which conferred protection against MERS-CoV challenge and reduced virus shedding in vaccinated camels [52 ] Therefore, this vaccine candidate may provide a means to prevent zoonotic transmission of the virus to the human population. Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice The recombinant Nterminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. Ongoing efforts to develop MERS-CoV vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. Extending on our current knowledge of MERS, vaccination of dromedary camels to induce mucosal immunity could be a promising approach to diminish MERS-CoV transmission to humans. In addition, it is equally important to develop vaccines for humans that induce broader reactivity against various coronaviruses to be prepared for a potential next CoV outbreak.


id: cord-283586-o8m6xdra
author: Spanakis, Nikolaos
date: 2014-12-31
txt: ./txt/cord-283586-o8m6xdra.txt
cache: ./cache/cord-283586-o8m6xdra.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.ijantimicag.2014.07.026
doi: 10.1016/j.ijantimicag.2014.07.026
summary:
  Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. An upsurge of Middle East respiratory syndrome coronavirus (MERS-CoV) infection has been recently described in countries of the Arabian Peninsula resulting in exported cases from these countries to the European Union [1] . Published reports propose the use of known antivirals based on extrapolation of data from: (i) the severe acute respiratory syndrome (SARS) epidemic that was also associated with the circulation of a novel coronavirus; (ii) in vitro data; (iii) animal experimental infections and therapy data; and (iv) limited clinical data for actual MERS-CoV infections [2] [3] [4] .

title:
  Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen

abstract:
  Abstract Serological, molecular and phylogenetic analyses of a recently imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) in Greece are reported. Although MERS-CoV remained detectable in the respiratory tract secretions of the patient until the fourth week of illness, viraemia was last detected 2 days after initiation of triple combination therapy with pegylated interferon, ribavirin and lopinavir/ritonavir, administered from Day 13 of illness. Phylogenetic analysis of the virus showed close similarity with other human MERS-CoVs from the recent Jeddah outbreak in Saudi Arabia. Immunoglobulin G (IgG) titres peaked 3 weeks after the onset of illness, whilst IgM levels remained constantly elevated during the follow-up period (second to fifth week of illness). Serological testing confirmed by virus neutralisation assay detected an additional case that was a close contact of the patient.


id: cord-284374-sqxlnk9e
author: Park, Jiyeon
date: 2020-01-15
txt: ./txt/cord-284374-sqxlnk9e.txt
cache: ./cache/cord-284374-sqxlnk9e.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41598-019-57216-x
doi: 10.1038/s41598-019-57216-x
summary:
  title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. Anesthesiologists were recommended to apply enhanced PPE (including PAPR from the middle of the outbreak) when managing all MERS-related patients because they were most directly exposed to the aerosol-producing high-risk procedures, such as endotracheal intubation and extubation. Almost all hospitals generally have positive-pressure operating rooms and they may experience an outbreak without facilities that are prepared for perioperative management of MERS patients, as our hospital did in 2015. First, although the previous guidelines recommended that asymptomatic MERS-exposed patients be managed as general patients undergoing surgery, we applied standard PPE to HCWs and we performed MERS-CoV PCR screening twice.

title:
  Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea

abstract:
  In 2015, we experienced the largest in-hospital Middle East respiratory syndrome (MERS) outbreak outside the Arabian Peninsula. We share the infection prevention measures for surgical procedures during the unexpected outbreak at our hospital. We reviewed all forms of related documents and collected information through interviews with healthcare workers of our hospital. After the onset of outbreak, a multidisciplinary team devised institutional MERS-control guidelines. Two standard operating rooms were converted to temporary negative-pressure rooms by physically decreasing the inflow air volume (−4.7 Pa in the main room and −1.2 Pa in the anteroom). Healthcare workers were equipped with standard or enhanced personal protective equipment according to the MERS-related patient’s profile and symptoms. Six MERS-related patients underwent emergency surgery, including four MERS-exposed and two MERS-confirmed patients. Negative conversion of MERS-CoV polymerase chain reaction tests was noticed for MERS-confirmed patients before surgery. MERS-exposed patients were also tested twice preoperatively, all of which were negative. All operative procedures in MERS-related patients were performed without specific adverse events or perioperative MERS transmission. Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries.


id: cord-286472-pqtem19t
title: MIDDLE EAST RESPIRATORY SYNDROME (MERS) CORONAVIRUS
author: McFee, R.B.
date: 2020-07-28
txt: ./txt/cord-286472-pqtem19t.txt
cache: ./cache/cord-286472-pqtem19t.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0011502920301152
doi: 10.1016/j.disamonth.2020.101053
abstract: nan
summary:
  This newly identified respiratory viral illness was caused by a novel coronavirus, which was initially designated as human betacoronavirus (2) (3) (4) (5) , but was eventually named Middle East Respiratory Syndrome Coronavirus (MERS CoV). It is important to consider multisystem function as well as pulmonary status in patients with severe respiratory illness, including suspected MERS CoV, especially those returning from regions where aggressive pathogens are noted. Patients recently returning from the Middle East, presenting with significant respiratory illness, with CT findings of peribronchial region abnormalities, organizing pneumonia, should be considered for MERS CoV infection, and if possible, queried about international travel and occupational exposures. Middle East Respiratory Syndrome Coronavirus (MERS CoV) Infection Feasibility, safety, clinical and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol


id: cord-286631-3fmg3scx
author: Pormohammad, Ali
date: 2020-06-05
txt: ./txt/cord-286631-3fmg3scx.txt
cache: ./cache/cord-286631-3fmg3scx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32502331/
doi: 10.1002/rmv.2112
summary:
  title: Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis The trigger for rapid screening and treatment of COVID-19 patients is based on clinical symptoms, laboratory, and radiographic findings that are similar to SARS and MERS infections. In this study, we attempted to distinguish the clinical symptoms, laboratory findings, radiographic signs, and outcomes of confirmed COVID-19, SARS, and MERS patients. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients

title:
  Comparison of confirmed COVID‐19 with SARS and MERS cases ‐ Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta‐analysis

abstract:
  INTRODUCTION: Within this large‐scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID‐19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed‐effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID‐19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID‐19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid‐19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X‐ray. The mortality rate in COVID‐19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID‐19 confirmed cases is lower than in SARS‐ and MERS‐infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.


id: cord-287156-3plpi6i9
title: Children in Coronaviruses’ Wonderland: What Clinicians Need to Know
author: Lassandro, Giuseppe
date: 2020-07-01
txt: ./txt/cord-287156-3plpi6i9.txt
cache: ./cache/cord-287156-3plpi6i9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32670520/
doi: 10.4084/mjhid.2020.042
summary:
  Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. 8, 9 Additionally, three HCoVs responsible for outbreaks involving high case fatality rates have been detected in humans in the last two decades: the severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the new coronavirus disease 2019 (COVID-19) ( Table 1) . Principal features of severe acute respiratory syndrome (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV and the most recent coronavirus disease 2019 (COVID19) . Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

abstract:
  Human coronaviruses (HCoVs) commonly cause mild upper-respiratory tract illnesses but can lead to more severe and diffusive diseases. A variety of signs and symptoms may be present, and infections can range in severity from the common cold and sore throat to more serious laryngeal or tracheal infections, bronchitis, and pneumonia. Among the seven coronaviruses that affect humans (SARS)-CoV, the Middle East respiratory syndrome (MERS)-CoV, and the most recent coronavirus disease 2019 (COVID-19) represent potential life-threatening diseases worldwide. In adults, they may cause severe pneumonia that evolves in respiratory distress syndrome and multiorgan failure with a high mortality rate. Children appear to be less susceptible to develop severe clinical disease and present usually with mild and aspecific symptoms similar to other respiratory infections typical of childhood. However, some children, such as infants, adolescents, or those with underlying diseases may be more at-risk categories and require greater caution from clinicians. Available data on pediatric coronavirus infections are rare and scattered in the literature. The purpose of this review is to provide to clinicians a complete and updated panel useful to recognize and characterize the broad spectrum of clinical manifestations of coronavirus infections in the pediatric age.


id: cord-287761-73qgx58i
author: Aly, Mahmoud
date: 2017-10-13
txt: ./txt/cord-287761-73qgx58i.txt
cache: ./cache/cord-287761-73qgx58i.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0183850
doi: 10.1371/journal.pone.0183850
summary:
  Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. The emergence of MERS-CoV dates back to July 2012 when an elderly patient of age 60 years died from an acute pneumonia in Saudi Arabia, and a new coronavirus strain was isolated from his lung tissue [1] . With regard to viral origin and transmission, the first case of MERS-CoV infection did not relate it to any particular contact with animals before the disease onset; however, other studies did link it to Dromedary camels [5] [6] [7] [8] .

title:
  Occurrence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) across the Gulf Corporation Council countries: Four years update

abstract:
  The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections has become a global issue of dire concerns. MERS-CoV infections have been identified in many countries all over the world whereas high level occurrences have been documented in the Middle East and Korea. MERS-CoV is mainly spreading across the geographical region of the Middle East, especially in the Arabian Peninsula, while some imported sporadic cases were reported from the Europe, North America, Africa, and lately Asia. The prevalence of MERS-CoV infections across the Gulf Corporation Council (GCC) countries still remains unclear. Therefore, the objective of the current study was to report the prevalence of MERS-CoV in the GCC countries and to also elucidate on its demographics in the Arabian Peninsula. To date, the World Health Organization (WHO) has reported 1,797 laboratory-confirmed cases of MERS-CoV infection since June 2012, involving 687 deaths in 27 different countries worldwide. Within a time span of 4 years from June 2012 to July 2016, we collect samples form MERS-CoV infected individuals from National Guard Hospital, Riyadh, and Ministry of health Saudi Arabia and other GCC countries. Our data comprise a total of 1550 cases (67.1% male and 32.9% female). The age-specific prevalence and distribution of MERS-CoV was as follow: <20 yrs (36 cases: 3.28%), 20–39 yrs (331 cases: 30.15%), 40–59 yrs (314 cases: 28.60%), and the highest-risk elderly group aged ≥60 yrs (417 cases: 37.98%). The case distribution among GCC countries was as follows: Saudi Arabia (1441 cases: 93%), Kuwait (4 cases: 0.3%), Bahrain (1 case: 0.1%), Oman (8 cases: 0.5%), Qatar (16 cases: 1.0%), and United Arab Emirates (80 cases: 5.2%). Thus, MERS-CoV was found to be more prevalent in Saudi Arabia especially in Riyadh, where 756 cases (52.4%) were the worst hit area of the country identified, followed by the western region Makkah where 298 cases (20.6%) were recorded. This prevalence update indicates that the Arabian Peninsula, particularly Saudi Arabia, is the hardest hit region regarding the emerging MERS-CoV infections worldwide. GCC countries including Saudi Arabia now have the infrastructure in place that allows physicians and scientific community to identify and immediately respond to the potential risks posed by new outbreaks of MERS-CoV infections in the region. Given the continuum of emergence and the large magnitude of the disease in our region, more studies will be required to bolster capabilities for timely detection and effective control and prevention of MERS-CoV in our region.


id: cord-293505-1t3hg4wi
author: Bernard-Stoecklin, Sibylle
date: 2019-05-14
txt: ./txt/cord-293505-1t3hg4wi.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/31089148/
doi: 10.1038/s41598-019-43586-9
summary:
  Such large healthcare-associated (HCA) outbreaks have mainly been limited to the Kingdom of Saudi Arabia (KSA) and the United Arabian Emirates (UAE) until the spring 2015, when a single imported case of MERS returning from the Middle East initiated a cluster of 186 cases in the Republic of Korea (ROK) across at least 17 hospitals and much of the country 18 . We analyzed epidemiological datasets of laboratory-confirmed MERS patients and focused our study on eleven healthcare-associated outbreaks that were reported in KSA and ROK since 2015, when policies and procedures for case identification and comprehensive contact identification and follow up became systematic and were implemented by affected countries. We defined a HCA-outbreak as the occurrence of 5 or more laboratory-confirmed MERS-CoV infections with reported epidemiologic links between cases and during which the human-to-human transmission events were documented within a single healthcare facility, with no more than 14 days apart between cases symptom onset.

title:
  Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017

abstract:
  Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.


id: cord-295633-vkjcheaz
author: Hao, Xin‐yan
date: 2019-10-30
txt: ./txt/cord-295633-vkjcheaz.txt
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url: https://doi.org/10.1002/ame2.12088
doi: 10.1002/ame2.12088
summary:
  After infection, we analyzed the mouse characteristics of weight loss, survival, viral replication, tissue pathology, viral antigen distribution, and cytokine and chemokine profiles, which provide additional data to investigate the pathogenesis of MERS-CoV-induced disease and evaluate relevant therapeutics and vaccines. Instillation control DMEM suspension To analyze clinical signs, weight loss, and survival On days 3, 5, 7, and 9 postinfection, three animals randomly selected from each group underwent necropsy to obtain tissue specimens for assessing viral distribution, associated histopathology, and cytokine levels using quantitative reverse transcription-PCR (qRT-PCR), hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). *P < .05, **P < .01, ***P < .001, and ****P < .0001 Mice in the instillation group died acutely or were euthanized when they researched 25% weight loss; these mice had a 0% survival rate by day 5, so no tissue lesion results were available on days 7 and 9 mice infected with MERS-CoV via the aerosol inhalation or intranasal instillation route, but no obvious lesions were found in other tissues.

title:
  The characteristics of hDPP4 transgenic mice subjected to aerosol MERS coronavirus infection via an animal nose‐only exposure device

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS‐CoV), which is not fully understood in regard to certain transmission routes and pathogenesis and lacks specific therapeutics and vaccines, poses a global threat to public health. METHODS: To simulate the clinical aerosol transmission route, hDPP4 transgenic mice were infected with MERS‐CoV by an animal nose‐only exposure device and compared with instillation‐inoculated mice. The challenged mice were observed for 14 consecutive days and necropsied on days 3, 5, 7, and 9 to analyze viral load, histopathology, viral antigen distribution, and cytokines in tissues. RESULTS: MERS‐CoV aerosol‐infected mice with an incubation period of 5‐7 days showed weight loss on days 7‐11, obvious lung lesions on day 7, high viral loads in the lungs on days 3‐9 and in the brain on days 7‐9, and 60% survival. MERS‐CoV instillation‐inoculated mice exhibited clinical signs on day 1, obvious lung lesions on days 3‐5, continuous weight loss, 0% survival by day 5, and high viral loads in the lungs and brain on days 3‐5. Viral antigen and high levels of proinflammatory cytokines and chemokines were detected in the aerosol and instillation groups. Disease, lung lesion, and viral replication progressions were slower in the MERS‐CoV aerosol‐infected mice than in the MERS‐CoV instillation‐inoculated mice. CONCLUSION: hDPP4 transgenic mice were successfully infected with MERS‐CoV aerosols via an animal nose‐only exposure device, and aerosol‐ and instillation‐infected mice simulated the clinical symptoms of moderate diffuse interstitial pneumonia. However, the transgenic mice exposed to aerosol MERS‐CoV developed disease and lung pathology progressions that more closely resembled those observed in humans.


id: cord-297062-dmiplvt2
title: Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients
author: Almekhlafi, Ghaleb A.
date: 2016-05-07
txt: ./txt/cord-297062-dmiplvt2.txt
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url: https://doi.org/10.1186/s13054-016-1303-8
doi: 10.1186/s13054-016-1303-8
summary:
  authors: Almekhlafi, Ghaleb A.; Albarrak, Mohammed M.; Mandourah, Yasser; Hassan, Sahar; Alwan, Abid; Abudayah, Abdullah; Altayyar, Sultan; Mustafa, Mohamed; Aldaghestani, Tareef; Alghamedi, Adnan; Talag, Ali; Malik, Muhammad K.; Omrani, Ali S.; Sakr, Yasser BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. We performed a retrospective study to describe the clinical features and outcomes of patients admitted to our ICU with laboratory-confirmed MERS-CoV infection. This report describes the clinical features and outcomes of 31critically ill patients with confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples. RESULTS: During the observation period, 31 patients were admitted with MERS-CoV infection (mean age 59 ± 20 years, 22 [71 %] males). Cough and tachypnea were reported in all patients; 22 (77.4 %) patients had bilateral pulmonary infiltrates. Invasive mechanical ventilation was applied in 27 (87.1 %) and vasopressor therapy in 25 (80.6 %) patients during the intensive care unit stay. Twenty-three (74.2 %) patients died in the ICU. Nonsurvivors were older, had greater APACHE II and SOFA scores on admission, and were more likely to have received invasive mechanical ventilation and vasopressor therapy. After adjustment for the severity of illness and the degree of organ dysfunction, the need for vasopressors was an independent risk factor for death in the ICU (odds ratio = 18.33, 95 % confidence interval: 1.11–302.1, P = 0.04). CONCLUSIONS: MERS-CoV infection requiring admission to the ICU is associated with high morbidity and mortality. The need for vasopressor therapy is the main risk factor for death in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1303-8) contains supplementary material, which is available to authorized users.


id: cord-298941-xf2ukinp
author: Al-Abdallat, Mohammad Mousa
date: 2014-05-14
txt: ./txt/cord-298941-xf2ukinp.txt
cache: ./cache/cord-298941-xf2ukinp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/24829216/
doi: 10.1093/cid/ciu359
summary:
  BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). Following the discovery of Middle East respiratory syndrome coronavirus (MERS-CoV) in September 2012 [2] , specimens from the 2 fatal cases in Jordan were retrospectively tested and both yielded positive results for MERS-CoV by real-time reverse transcription polymerase chain reaction (rRT-PCR), and were reported to the World Health Organization (WHO). Using newly developed serologic assays to determine MERS-CoV antibody responses among case contacts in this outbreak, epidemiologists from the JMoH, US Centers for Disease Control and Prevention (CDC), and regional partners conducted a retrospective seroepidemiologic investigation to (1) confirm whether surviving outbreak members had presence of antibodies to MERS-CoV, (2) ascertain whether viral transmission occurred among household contacts or to other healthcare personnel, and (3) describe the clinical features of all detected MERS-CoV infections in Jordan.

title:
  Hospital-Associated Outbreak of Middle East Respiratory Syndrome Coronavirus: A Serologic, Epidemiologic, and Clinical Description

abstract:
  BACKGROUND: In April 2012, the Jordan Ministry of Health investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; 2 fatal cases were retrospectively confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) to be the first detected cases of Middle East respiratory syndrome (MERS-CoV). METHODS: Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical record reviews, and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using 3 US Centers for Disease Control and Prevention serologic tests for detection of anti–MERS-CoV antibodies. RESULTS: Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti–MERS-CoV antibodies by at least 2 of 3 serologic tests, in addition to 2 fatal cases identified by rRT-PCR. The case-fatality rate among the 9 total cases was 22%. Six subjects were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at 2 transfer hospitals having acceptable infection control practices. CONCLUSIONS: Novel serologic tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts in a Jordanian hospital-associated respiratory illness outbreak in April 2012, resulting in a total of 9 test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most subjects had no major, underlying medical conditions; none were on hemodialysis. Our observed case-fatality rate was lower than has been reported from outbreaks elsewhere.


id: cord-299519-hfgmmuy6
title: Severe Middle East Respiratory Syndrome (MERS) Pneumonia
author: Alenazi, Thamer H.
date: 2019-10-26
txt: ./txt/cord-299519-hfgmmuy6.txt
cache: ./cache/cord-299519-hfgmmuy6.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128012383114886
doi: 10.1016/b978-0-12-801238-3.11488-6
summary:
  A febrile acute respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome) that cannot be explained fully by any other etiology AND The person resides or traveled in the Middle East, or in countries where MERS-CoV is known to be circulating in dromedary camels or where human infections have recently occurred AND Testing for MERS-CoV is inconclusive. Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: An observational study Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: A report of 5 cases from Saudi Arabia An observational, laboratory-based study of outbreaks of middle East respiratory syndrome coronavirus in Jeddah and Riyadh, kingdom of Saudi Arabia Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: A retrospective cohort study

abstract:
  Middle East Respiratory Syndrome (MERS) is a viral respiratory infection, which ranges from asymptomatic infection to severe pneumonia and multiorgan failure, caused by a novel coronavirus named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Majority of cases have been reported from Saudi Arabia. MERS cases occur as sporadic cases or as clusters or hospital outbreaks. Dromedary camels are thought to be a host for MERS-CoV. Direct contact with dromedary camels within 14 days prior to infection was identified as an independent risk factor for MERS. Diagnosis of MERS is based on a positive real-time reverse transcriptase polymerase chain reaction (rRT-PCR), obtained from a respiratory specimen. The mainstay of management of MERS-CoV infection is supportive care. There is no specific antiviral therapy for MERS-CoV infection at present, although several modalities of treatment options have been examined or are under investigation.


id: cord-300536-8okuomi6
title: Unique Challenges to Control the Spread of COVID-19 in the Middle East
author: Baloch, Zulqarnain
date: 2020-07-13
txt: ./txt/cord-300536-8okuomi6.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32690454/
doi: 10.1016/j.jiph.2020.06.034
summary:
  These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. Besides weakening healthcare systems, wars and conflicts in the Middle East have also led to large-scale humanitarian crises. In Iran, the early COVID-19 cases were recorded in Qom (Fig. 3B) , a city that attracts millions of pilgrims from countries including Lebanon, As pilgrims concentrating on religious rituals, there are close contacts among worshipers and insufficient self-protective measures, and therefore amplify the risk of transmission and potential super spreading of SARS-CoV-2 [24] . These include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings.

abstract:
  The COVID-19 pandemic is spreading at unprecedented pace among the Middle East and neighboring countries. This region is geographically, economically, politically, culturally and religiously a very sensitive area, which impose unique challenges for effective control of this epidemic. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These factors are interrelated and collectively determine the response to the pandemic in this region. Here, we in-depth emphasize these challenges and take a glimpse of possible solutions towards mitigating the spread of COVID-19.


id: cord-303272-1w8epdht
author: Reusken, Chantal BEM
date: 2013-08-09
txt: ./txt/cord-303272-1w8epdht.txt
cache: ./cache/cord-303272-1w8epdht.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1473309913701646
doi: 10.1016/s1473-3099(13)70164-6
summary:
  title: Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. We tested the sera for the presence of IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray. plaque reduction neutralisation tests for bovine coronavirus and MERS-CoV (B): two representative sera are shown (numbers 15 and 5, corresponding to camel ID numbers in table 2) in dilutions of 1/40, 1/160, and 1/640 as well as the virus input control. Sera were tested for IgG antibodies reactive with MERS-CoV, SARS-CoV, and human coronavirus OC43 S1 antigens in a protein microarray (fi gure 1).

title:
  Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study

abstract:
  BACKGROUND: A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock. METHODS: We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus. FINDINGS: 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. INTERPRETATION: MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. FUNDING: European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.


id: cord-304054-sn7rswab
title: Chapter 8 The Middle East Respiratory Syndrome Coronavirus: An Emerging Virus of Global Threat
author: Khan, Gulfaraz
date: 2020-12-31
txt: ./txt/cord-304054-sn7rswab.txt
cache: ./cache/cord-304054-sn7rswab.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128194003000089
doi: 10.1016/b978-0-12-819400-3.00008-9
summary:
  Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Although the natural reservoir of MERS-CoV infection and mode of transmission to humans is not known, one factor appears to be common to all primary cases; they are epidemiologically linked to the Middle East region. Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Middle East respiratory syndrome coronavirus infection during pregnancy: a report of 5 cases from Saudi Arabia Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission Transmission of Middle East Respiratory syndrome coronavirus infections in healthcare settings

abstract:
  Abstract Middle East respiratory syndrome (MERS) is a viral respiratory illness caused by a coronavirus (CoV), first identified in Saudi Arabia in 2012. Since then, almost 2000 cases have been reported from 27 countries, with Saudi Arabia being the epicenter. This newly emerging virus is highly pathogenic and has a case mortality rate of 35%. It is similar to the CoV causing severe acute respiratory syndrome CoV (SARS-CoV) in that both belong to the genus beta CoVs that are of zoonotic origin and cause lower respiratory infection. The natural reservoir for MERS-CoV remains unknown. Serological studies indicate that most dromedary camels in the Middle East have been infected with this virus, and they maybe the potential intermediate host. However, the mode of transmission from camels to humans is poorly understood. The majority of confirmed human cases have resulted from human-to-human transmission, most probably via respiratory route. Patients most at risk of developing severe MERS-CoV infection appear to be those with underlying conditions such as diabetes, hypertension, obesity, cardiac diseases, chronic respiratory diseases, and cancer. Unlike SARS-CoV, MERS-CoV is considered an ongoing public health problem, particularly for the Middle East region. In this chapter, we outline the prevailing information regarding the emergence and epidemiology of this virus, its mode of transmission and pathogenicity, its clinical features, and the potential strategies for prevention.


id: cord-305317-08a1oin2
title: Middle East respiratory syndrome coronavirus: Implications for health care facilities
author: Maltezou, Helena C.
date: 2014-12-31
txt: ./txt/cord-305317-08a1oin2.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0196655314009316
doi: 10.1016/j.ajic.2014.06.019
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus of the Coronaviridae family that causes a severe respiratory disease with a high case fatality rate. 2, 3, 6, 8, 22, 24 During the largest so farepublished outbreak of MERS-CoV that occurred in Al-Hasa, Saudi Arabia, in 2013, 4 health care facilities were affected through transfer of patients but also possibly because of repeated introductions of cases from the community. Studies about the effectiveness of infection control measures will provide answers and eventually promote safety in health care facilities both for patients and HCWs. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Investigation of an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Interim infection prevention and control recommendations for hospitalized patients with Middle East respiratory syndrome coronavirus (MERS-CoV)

abstract:
  Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus that causes a severe respiratory disease with high case fatality rate. Starting in March 2014, a dramatic increase of cases has occurred in the Arabian Peninsula, many of which were acquired in health care settings. As of May 9, 2014, 536 laboratory-confirmed cases and 145 deaths have been reported globally. Methods Review of publicly available data about MERS-CoV health care–associated transmission. Results We identified 11 events of possible or confirmed health care–associated transmission with high morbidity and mortality, mainly among patients with comorbidities. Health care workers are also frequently affected; however, they tend to have milder symptoms and better prognosis. Gaps in infection control were noted in all events. Currently, health care–associated outbreaks are playing a pivotal role in the evolution of the MERS-CoV epidemic in countries in the Arabian Peninsula. Conclusion There is a need to increase infection control capacity in affected areas and areas at increased risk of being affected to prevent transmission in health care settings. Vaccines and antiviral agents are urgently needed. Overall, our knowledge about the epidemiologic characteristics of MERS-CoV that impact health care transmission is very limited. As the MERS-CoV epidemic continues to evolve, issues concerning best infection control measures will arise, and studies to better define their effectiveness in real life are needed.


id: cord-306004-amv0los1
title: Host Determinants of MERS-CoV Transmission and Pathogenesis
author: Widagdo, W.
date: 2019-03-19
url: https://www.ncbi.nlm.nih.gov/pubmed/30893947/
doi: 10.3390/v11030280
abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that causes respiratory infection in humans, ranging from asymptomatic to severe pneumonia. In dromedary camels, the virus only causes a mild infection but it spreads efficiently between animals. Differences in the behavior of the virus observed between individuals, as well as between humans and dromedary camels, highlight the role of host factors in MERS-CoV pathogenesis and transmission. One of these host factors, the MERS-CoV receptor dipeptidyl peptidase-4 (DPP4), may be a critical determinant because it is variably expressed in MERS-CoV-susceptible species as well as in humans. This could partially explain inter- and intraspecies differences in the tropism, pathogenesis, and transmissibility of MERS-CoV. In this review, we explore the role of DPP4 and other host factors in MERS-CoV transmission and pathogenesis—such as sialic acids, host proteases, and interferons. Further characterization of these host determinants may potentially offer novel insights to develop intervention strategies to tackle ongoing outbreaks.


id: cord-307995-8q7efrqk
title: Middle East respiratory syndrome coronavirus: current situation and travel-associated concerns
author: Al-Tawfiq, Jaffar A.
date: 2016-05-04
txt: ./txt/cord-307995-8q7efrqk.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11684-016-0446-y
doi: 10.1007/s11684-016-0446-y
summary:
  Middle East respiratory syndrome coronavirus (MERS-CoV): summary and risk assessment of current situation in the Republic of Korea and China -as of 19 Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study A family cluster of Middle East Respiratory syndrome coronavirus infections related to a likely unrecognized asymptomatic or mild case Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study KSA MERS-CoV Investigation Team.Hospital outbreak of Middle East respiratory syndrome coronavirus Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study

abstract:
  The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 brought back memories of the occurrence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002. More than 1500 MERS-CoV cases were recorded in 42 months with a case fatality rate (CFR) of 40%. Meanwhile, 8000 cases of SARS-CoV were confirmed in six months with a CFR of 10%. The clinical presentation of MERS-CoV ranges from mild and non-specific presentation to progressive and severe pneumonia. No predictive signs or symptoms exist to differentiate MERS-CoV from community-acquired pneumonia in hospitalized patients. An apparent heterogeneity was observed in transmission. Most MERS-CoV cases were secondary to large outbreaks in healthcare settings. These cases were secondary to community-acquired cases, which may also cause family outbreaks. Travel-associated MERS infection remains low. However, the virus exhibited a clear tendency to cause large outbreaks outside the Arabian Peninsula as exemplified by the outbreak in the Republic of Korea. In this review, we summarize the current knowledge about MERS-CoV and highlight travel-related issues.


id: cord-309621-6jj19xpr
author: Yu, Pin
date: 2017-02-24
txt: ./txt/cord-309621-6jj19xpr.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28234937/
doi: 10.1371/journal.pone.0172093
summary:
  The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. Although there have been several studies in animal models on the pathogenic mechanisms of MERS-CoV infection, little is known about the comparative pathology and inflammatory cell response in rhesus macaques or common marmosets infected with this virus. Pathological findings in the rhesus macaque tissues HE stained tissues from rhesus macaques experimentally infected with MERS-CoV demonstrate that MERS-CoV induces lesions that are primarily observed in the lungs, with varying degrees of inflammation, interstitial pneumonia (Fig 1A) , pulmonary oedema (Fig 1B) , haemorrhaging, degeneration and necrosis of pneumocytes and bronchial epithelial cells (Fig 1C) , and the infiltration of inflammatory cells. Using immunohistochemical techniques and an ISH analysis, we confirmed that MERS-CoV protein and viral RNA were distributed in the lungs of rhesus macaques and common marmosets and that they were primarily located in the pneumocytes and inflammatory cells.

title:
  Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

abstract:
  Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments.


id: cord-311937-6hadssmh
author: Sherbini, Nahid
date: 2016-06-11
txt: ./txt/cord-311937-6hadssmh.txt
cache: ./cache/cord-311937-6hadssmh.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S2210600615300927
doi: 10.1016/j.jegh.2016.05.002
summary:
  title: Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data METHODS: A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). Epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) was expanded after exploring the large hospital outbreak in Al-Hasa, Saudi Arabia [2] . We obtained data about demographic characteristics, clinical presentation, laboratory results, diagnosis, incubation period, smoking history, comorbidities, and history of contact with camels or MERS-CoV positive patients in regions within the Madinah area. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection

title:
  Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging virus respiratory infection. It has a high mortality rate and a wide spectrum of clinical features. This study describes the clinical characteristics and outcome of MERS infected patients. METHODS: A retrospective study was conducted of all confirmed MERS-CoV infections from March 2014 to May 2014 at two tertiary care hospitals in Al-Madinah region (Saudi Arabia). We gathered data about demographic, clinical presentation, and factors associated with severity and mortality. RESULTS: A total of 29 cases were identified; 20 males (69%) and nine females (31%), age 45 ± 12 years. The death rate was higher for men (52%) than for women (23%). Initial presentation was fever in 22 (75%) cases, cough in 20 (69%) cases, and shortness of breath in 20 (69%) cases. Associated comorbidities were diabetes mellitus in nine (31%) patients and chronic kidney disease (CKD) in eight (27%) patients. Duration of symptoms before hospitalization ranged from 2.9 days to 5 days. Elevated liver enzymes were present in 14 (50%) patients and impaired renal profile present in eight (27%) patients. We also describe in this study radiological patterns and factors associated with mortality. CONCLUSION: MERS-CoV infection transmission continues to occur as clusters in healthcare facilities. The frequency of cases and deaths is higher among men than women and among patients with comorbidities.


id: cord-312741-0au4nctt
title: Coronavirus in human diseases: Mechanisms and advances in clinical treatment
author: Lin, Panpan
date: 2020-10-01
url: https://www.ncbi.nlm.nih.gov/pubmed/33173860/
doi: 10.1002/mco2.26
abstract:
  Coronaviruses (CoVs), a subfamily of coronavirinae, are a panel of single‐stranded RNA virus. Human coronavirus (HCoV) strains (HCoV‐229E, HCoV‐OC43, HCoV‐HKU1, HCoV‐NL63) usually cause mild upper respiratory diseases and are believed to be harmless. However, other HCoVs, associated with severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID‐19, have been identified as important pathogens due to their potent infectivity and lethality worldwide. Moreover, currently, no effective antiviral drugs treatments are available so far. In this review, we summarize the biological characters of HCoVs, their association with human diseases, and current therapeutic options for the three severe HCoVs. We also highlight the discussion about novel treatment strategies for HCoVs infections.


id: cord-314651-e4uaw5fy
author: Zhao, Guangyu
date: 2015-12-23
txt: ./txt/cord-314651-e4uaw5fy.txt
cache: ./cache/cord-314651-e4uaw5fy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26701103/
doi: 10.1371/journal.pone.0145561
summary:
  After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. To assess viral replication and histopathologic damage following MERS-CoV infection, mice were euthanized with overdose inhalational carbon dioxide, and tissues included lungs, kidneys, livers, spleens, intestines and brains were harvested on indicated time points. Although a transgenic mouse model expressing human DPP4 was also established, and its immune response was studied after infection with MERS-CoV [16] , the transgenic mice in the study died on day 6 with only progressive pneumonia and mild perivascular cuffing in brain, and no neurological disorder or other multi-organ damage was observed.

title:
  Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus

abstract:
  The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.


id: cord-316194-jnw8gr7e
title: Chapter 61 Disorders of the Ear
author: Sifuentes, Monica
date: 2005-12-31
txt: ./txt/cord-316194-jnw8gr7e.txt
cache: ./cache/cord-316194-jnw8gr7e.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780323011990500669
doi: 10.1016/b978-0-323-01199-0.50066-9
abstract: nan
summary:
  Children differ from adults in that complications are more likely to occur from AOM than chronic ear disease and often are the result of delayed treatment. Children with AOM usually have fluid present in the mastoid air cells because of the direct connection with the middle ear ( Fig. 61-1) . The most common suppurative intracranial complication of OM and mastoiditis is bacterial meningitis, although its incidence has decreased dramatically since the advent of antibiotic therapy for acute infections and routine immunization against Haemophilus influenzae type B. Therapeutic goals for infants and young children with OM are to treat acute infections appropriately and prevent recurrent and chronic middle ear disease, reducing the morbidity and mortality associated with intratemporal and intracranial complications. Children with uncomplicated AOM generally have a favorable outcome depending on their age at diagnosis, frequency of infections, and length of time for fluid in the middle ear to resolve.


id: cord-316392-bp988sir
title: Severe Pneumonia and Human Bocavirus in Adult
author: Kupfer, Bernd
date: 2006-10-17
txt: ./txt/cord-316392-bp988sir.txt
cache: ./cache/cord-316392-bp988sir.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17176591/
doi: 10.3201/eid1210.060520
abstract: nan
summary:
  To the Editor: The newly identified human bocavirus (hBoV), a member of the Parvovirus family, is suspected to infect the cells of the respiratory tract and thus may be an etiologic agent of respiratory disease in humans (1) . Retrospectively, however, human bocavirus DNA in the archived BAL strongly suggests that pulmonary symptoms were caused by this agent rather than by a yet unknown bacterial or fungal infection. This finding led to the conclusion that a "new" virus that induces the identical clinical symptoms, like the human bocavirus, may also contribute to severe respiratory infections. Besides the first proof for visceral leishmaniasis in paleopathology, we provide evidence that leishmaniasis was present in Nubia in the early Christian period and that the organism also infected ancient Egyptians, probably because of close trading contacts to Nubia, during the Middle Kingdom. Detection of human bocavirus in Japanese children with lower respiratory tract infections


id: cord-317688-mr851682
title: Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea
author: Oh, Myoung-don
date: 2018-02-27
txt: ./txt/cord-317688-mr851682.txt
cache: ./cache/cord-317688-mr851682.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3904/kjim.2018.031
doi: 10.3904/kjim.2018.031
summary:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in September 2012 [1] . The first patient (index case) with MERS-CoV infection was a 68-year-old Korean man returning from the Middle East. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea Clinical implications of 5 cases of Middle East respiratory syndrome coronavirus infection in a South Korean outbreak Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report

abstract:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.


id: cord-318181-xxc7vdnt
author: Ahmed, Anwar E.
date: 2018-03-14
txt: ./txt/cord-318181-xxc7vdnt.txt
cache: ./cache/cord-318181-xxc7vdnt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29550445/
doi: 10.1016/j.ijid.2018.03.005
summary:
  A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. Nineteen predictive variables were included: age, sex, fever (temperature !38 C), one composite respiratory symptom (the presence of cough, bloody cough, shortness of breath, or chest pain), one composite gastrointestinal symptoms (the presence of diarrhea, vomiting, or nausea), seven MERS-CoV potential risk factors (contact with sick patients or camels, severe illness (defined according to the patient''s clinical status, ''yes/no'', which is based on clinical judgment), diabetes, lung disease, liver disease, renal disease, and heart disease), and seven laboratory measurements (white blood cell (WBC) count (Â10 9 /l), platelets (Â10 9 /l), creatinine (mmol/l), bilirubin (mmol/l), alanine aminotransferase (ALT; U/l), aspartate aminotransferase (AST; U/l), and albumin (g/ l)).

title:
  Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

abstract:
  BACKGROUND: The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. METHODS: A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. RESULTS: A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p = 0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. CONCLUSIONS: This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary.


id: cord-318585-cp76qr9f
author: Matsuyama, Ryota
date: 2016-11-29
txt: ./txt/cord-318585-cp76qr9f.txt
cache: ./cache/cord-318585-cp76qr9f.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27899100/
doi: 10.1186/s12889-016-3881-4
summary:
  BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. PICO statement: Our study question is focused on laboratory confirmed cases of MERS regardless of their treatment status, and thus, involves only retrospective observational studies, measuring their risks of admission to Intensive Care Unit (ICU) and death and comparing those risks by age, gender and underlying comorbidities. The present study systematically reviewed the risk of severe manifestations and death by MERS by systematically searching and analyzing published articles from the KSA and the ROK and calculating not only the CFR but [16] . For Fig. 4 Estimated risks associated with Middle East respiratory syndrome (MERS) by study design.

title:
  Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis

abstract:
  BACKGROUND: While the risk of severe complications of Middle East respiratory syndrome (MERS) and its determinants have been explored in previous studies, a systematic analysis of published articles with different designs and populations has yet to be conducted. The present study aimed to systematically review the risk of death associated with MERS as well as risk factors for associated complications. METHODS: PubMed and Web of Science databases were searched for clinical and epidemiological studies on confirmed cases of MERS. Eligible articles reported clinical outcomes, especially severe complications or death associated with MERS. Risks of admission to intensive care unit (ICU), mechanical ventilation and death were estimated. Subsequently, potential associations between MERS-associated death and age, sex, underlying medical conditions and study design were explored. RESULTS: A total of 25 eligible articles were identified. The case fatality risk ranged from 14.5 to 100%, with the pooled estimate at 39.1%. The risks of ICU admission and mechanical ventilation ranged from 44.4 to 100% and from 25.0 to 100%, with pooled estimates at 78.2 and 73.0%, respectively. These risks showed a substantial heterogeneity among the identified studies, and appeared to be the highest in case studies focusing on ICU cases. We identified older age, male sex and underlying medical conditions, including diabetes mellitus, renal disease, respiratory disease, heart disease and hypertension, as clinical predictors of death associated with MERS. In ICU case studies, the expected odds ratios (OR) of death among patients with underlying heart disease or renal disease to patients without such comorbidities were 0.6 (95% Confidence Interval (CI): 0.1, 4.3) and 0.6 (95% CI: 0.0, 2.1), respectively, while the ORs were 3.8 (95% CI: 3.4, 4.2) and 2.4 (95% CI: 2.0, 2.9), respectively, in studies with other types of designs. CONCLUSIONS: The heterogeneity for the risk of death and severe manifestations was substantially high among the studies, and varying study designs was one of the underlying reasons for this heterogeneity. A statistical estimation of the risk of MERS death and identification of risk factors must be conducted, particularly considering the study design and potential biases associated with case detection and diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-016-3881-4) contains supplementary material, which is available to authorized users.


id: cord-318872-0e5zjaz1
title: MERS transmission and risk factors: a systematic review
author: Park, Ji-Eun
date: 2018-05-02
txt: ./txt/cord-318872-0e5zjaz1.txt
cache: ./cache/cord-318872-0e5zjaz1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29716568/
doi: 10.1186/s12889-018-5484-8
summary:
  BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. The incubation period was reported to be 6.83-7 days in South Korea [4, 5] , but 5.5 in a study using data from multiple areas [6] and 5.2 in Saudi Arabia [7] . Although one study from Saudi Arabia reported longer than 17 days from onset to death [36] , Sha et al., comparing data between the Middle East and South Korea, reported similar periods of 11.5 and 11 days, respectively [29] . Mortality of MERS patients was found to be 20.4% in South Korea based on a report including all cases [27] , but most studies from Saudi Arabia reported higher rates, from 22 to 69.2% [7, 22, 33, [37] [38] [39] . Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea

abstract:
  BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. METHOD: We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. RESULT: A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R(0) value in Saudi Arabia was < 1 in all but one study, in South Korea, the R(0) value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality. CONCLUSION: The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.


id: cord-319877-izn315hb
title: SARS and MERS: recent insights into emerging coronaviruses
author: de Wit, Emmie
date: 2016-06-27
url: https://doi.org/10.1038/nrmicro.2016.81
doi: 10.1038/nrmicro.2016.81
abstract:
  The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.


id: cord-322760-tsxniu3j
author: Sha, Jianping
date: 2016-09-23
url: https://www.ncbi.nlm.nih.gov/pubmed/27664026/
doi: 10.1007/s00705-016-3062-x
title:
  Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea

abstract:
  Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012. The largest known outbreak outside the Middle East occurred in South Korea in 2015. As of 29 June 2016, 1769 laboratory-confirmed cases (630 deaths; 35.6 % case fatality rate [CFR]) had been reported from 26 countries, particularly in the Middle East. However, the CFR for hospital outbreaks was higher than that of family clusters in the Middle East and Korea. Here, we compared the mortality rates for 51 nosocomial outbreaks in the Middle East and one outbreak of MERS-CoV in South Korea. Our findings showed the CFR in the Middle East was much higher than that in South Korea (25.9 % [56/216] vs. 13.8 % [24/174], p = 0.003). Infected individuals who died were, on average, older than those who survived in both the Middle East (64 years [25–98] vs. 46 years [2–85], p = 0.000) and South Korea (68 years [49–82] vs. 53.5 years [16–87], p = 0.000). Similarly, the co-morbidity rates for the fatal cases were statistically higher than for the nonfatal cases in both the Middle East (64.3 % [36/56] vs. 28.1 % [45/160], p = 0.000) and South Korea (45.8 % [11/24] vs. 12.0 % [18/150], p = 0.000). The median number of days from onset to confirmation of infection in the fatal cases was longer than that for survivors from the Middle East (8 days [1–47] vs. 4 days [0–14], p = 0.009). Thus, older age, pre-existing concurrent diseases, and delayed confirmation increase the odds of a fatal outcome in nosocomial MERS-CoV outbreaks in the Middle East and South Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-3062-x) contains supplementary material, which is available to authorized users.


id: cord-323125-qtlevnbt
author: Al Hosani, Farida Ismail
date: 2019-02-01
txt: ./txt/cord-323125-qtlevnbt.txt
cache: ./cache/cord-323125-qtlevnbt.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/cid/ciy503
doi: 10.1093/cid/ciy503
summary:
  BACKGROUND: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. METHODS: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. In this investigation, we use serological detection of MERS-CoV antibodies to evaluate if asymptomatic or mildly ill case patients had detectable MERS-CoV antibodies, estimate transmission rates from known cases to their household contacts, and identify potential risk factors. For each MERS-CoV case identified in the investigation, clinical information, including symptoms, was collected using the International Severe Acute Respiratory and Emerging Infection Consortium form, which was filled out in real time by healthcare providers and subsequently verified by retrospective chart review.

title:
  Serologic Follow-up of Middle East Respiratory Syndrome Coronavirus Cases and Contacts—Abu Dhabi, United Arab Emirates

abstract:
  BACKGROUND: Although there is evidence of person-to-person transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in household and healthcare settings, more data are needed to describe and better understand the risk factors and transmission routes in both settings, as well as the extent to which disease severity affects transmission. METHODS: A seroepidemiological investigation was conducted among MERS-CoV case patients (cases) and their household contacts to investigate transmission risk in Abu Dhabi, United Arab Emirates. Cases diagnosed between 1 January 2013 and 9 May 2014 and their household contacts were approached for enrollment. Demographic, clinical, and exposure history data were collected. Sera were screened by MERS-CoV nucleocapsid protein enzyme-linked immunosorbent assay and indirect immunofluorescence, with results confirmed by microneutralization assay. RESULTS: Thirty-one of 34 (91%) case patients were asymptomatic or mildly symptomatic and did not require oxygen during hospitalization. MERS-CoV antibodies were detected in 13 of 24 (54%) case patients with available sera, including 1 severely symptomatic, 9 mildly symptomatic, and 3 asymptomatic case patients. No serologic evidence of MERS-CoV transmission was found among 105 household contacts with available sera. CONCLUSIONS: Transmission of MERS-CoV was not documented in this investigation of mostly asymptomatic and mildly symptomatic cases and their household contacts. These results have implications for clinical management of cases and formulation of isolation policies to reduce the risk of transmission.


id: cord-323133-gdg50omp
title: The pathogens profile in children with otitis media with effusion and adenoid hypertrophy
author: Buzatto, G. P.
date: 2017-02-23
txt: ./txt/cord-323133-gdg50omp.txt
cache: ./cache/cord-323133-gdg50omp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1371/journal.pone.0171049
doi: 10.1371/journal.pone.0171049
summary:
  OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Therefore, the present study was carried out to compare the detection of common respiratory viruses and bacteria in adenoids and middle ear fluid in children with OME and in controls. In our study, we used a sensitive method to detect nucleic acid of a comprehensive panel of respiratory viruses and bacteria to compare the microbial colonization of adenoid and its correspondence in the middle ear in both OME children and controls. Concluding, in children with OME and adenoid hypertrophy we observed higher detection rates of potentially pathogenic bacteria, but not respiratory viruses, by real-time PCR in middle ear samples, as compared to control patients without adenoid hypertrophy.

abstract:
  OBJECTIVES: To evaluate the presence of viruses and bacteria in middle ear and adenoids of patients with and without otitis media with effusion (OME). METHODS: Adenoid samples and middle ear washes (MEW) were obtained from children with OME associated with adenoid hypertrophy undergoing adenoidectomy and tympanostomy, and compared to those obtained from patients undergoing cochlear implant surgery, as a control group. Specific DNA or RNA of 9 respiratory viruses (rhinovirus, influenza virus, picornavirus, syncytial respiratory virus, metapneumovirus, coronavirus, enterovirus, adenovirus and bocavirus) and 5 bacteria (S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa and S. aureus) were extracted and quantified by real-time PCR. RESULTS: 37 OME and 14 cochlear implant children were included in the study. At the adenoid, virus and bacteria were similarly detected in both OME and control patients. At the middle ear washes, however, a higher prevalence of bacteria was observed in patients with OME (p = 0.01). S. pneumoniae (p = 0.01) and M. catarrhalis (p = 0.022) were the bacteria responsible for this difference. Although total virus detection was not statistically different from controls at the middle ear washes (p = 0.065), adenovirus was detected in higher proportions in adenoid samples of OME patients than controls (p = 0.019). CONCLUSIONS: Despite both OME and control patients presented similar rates of viruses and bacteria at the adenoid, children with OME presented higher prevalence of S. pneumonia, M. catarrhalis in middle ear and adenovirus in adenoids when compared to controls. These findings could suggest that these pathogens could contribute to the fluid persistence in the middle ear.


id: cord-323428-jd91k19z
author: Ababneh, Mustafa
date: 2019-10-11
txt: ./txt/cord-323428-jd91k19z.txt
cache: ./cache/cord-323428-jd91k19z.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.14202/vetworld.2019.1554-1562
doi: 10.14202/vetworld.2019.1554-1562
summary:
  CONCLUSION: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. Distribution and expression of the S1 subunit of the MERS-CoV spike protein in mice tissues were detected at weeks 3 and 5 post first immunization in the kidneys and lungs of the vaccinated group but not in control groups using conventional PCR (Figure-1 ). In contrast, IL-4 production in cell culture showed a significant increase in control animals after antigen stimulation, while the production of this cytokine was significantly decreased in the At week 4, the fold change in IFN-γ gene expression was significantly higher in the Ad-Middle East respiratory syndrome (MERS)-S1 group than that of both control groups (Ad-cytomegalovirus [CMV] and phosphate-buffered saline).

title:
  Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice

abstract:
  BACKGROUND AND AIM: Middle East respiratory syndrome coronavirus (MERS-CoV) has rapidly spread throughout the Middle East since its discovery in 2012. The virus poses a significant global public health threat with potentially devastating effects. In this study, a recombinant adenoviral-based vaccine encoding the spike 1 (S1) subunit of the MERS-CoV genome was constructed, and its humoral, and cellular immune responses were evaluated in mice. MATERIALS AND METHODS: Mice were immunized initially by intramuscular injection and boosted 3 weeks later by intranasal application. Expression of the S1 protein in the lungs and kidneys was detected using conventional polymerase chain reaction (PCR) and immunohistochemistry (IHC) targeting specific regions within the S1 subunit at weeks 3, 4, 5, and 6 after the first vaccination. Antigen-specific humoral and cellular immune responses were evaluated in serum and in cell culture following in vitro stimulation with a specific 9-mer epitope within the S1 protein (CYSSLILDY). RESULTS: S1 protein expression was only detected by IHC in the kidneys of the Ad-MERS-S1 group at week 6 from first immunization, and in both lungs and kidneys of Ad-MERS-S1 group by conventional PCR at weeks 3 and 5 post-prime. The vaccine elicited a specific S1-immunoglobulin G antibody response, which was detected in the sera of the vaccinated mice at weeks 4 and 6 from the onset of the first immunization. There was a significant increase in the amount of Th1-related cytokines (interferon-γ and interleukin [IL] 12), and a significant decrease in the Th2-related cytokine IL-4 in splenocyte cell culture of the vaccinated group compared with the control groups. CONCLUSION: The results of this study suggest that this recombinant adenovirus vaccine encoding the S1 subunit of MERS-CoV elicits potentially protective antigen-specific humoral and cellular immune responses in mice. This study demonstrates a promising vaccine for the control and/or prevention of MERS-CoV infection in humans.


id: cord-329190-kv9n2qj3
title: A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective
author: Rabaan, Ali A.
date: 2017-09-01
txt: ./txt/cord-329190-kv9n2qj3.txt
cache: ./cache/cord-329190-kv9n2qj3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1099/jmm.0.000565
doi: 10.1099/jmm.0.000565
summary:
  The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The Medline database was searched using combinations and variations of terms, including ''Middle East respiratory syndrome coronavirus'', ''MERS-CoV'', ''SARS'', ''therapy'', ''molecular'', ''vaccine'', ''prophylactic'', ''S protein'', ''DPP4'', ''heptad repeat'', ''protease'', ''inhibitor'', ''anti-viral'', ''broad-spectrum'', ''interferon'', ''convalescent plasma'', ''lopinavir ritonavir'', ''antibodies'', ''antiviral peptides'' and ''live attenuated viruses''. A position paper on the evidence base for specific MERS-CoV therapies, published by Public Health England (PHE) and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO), suggested that benefit was likely to exceed risk for convalescent plasma, lopinavir-ritonavir, IFNs and monoclonal/polyclonal antibodies, while, by contrast, for ribavirin monotherapy and corticosteroids it was considered that the risks would outweigh the benefits [42] .

abstract:
  There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir–ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required. We examine existing and potential therapies and vaccines from a molecular perspective. These include viral S protein targeting; inhibitors of host proteases, including TMPRSS2, cathepsin L and furin protease, and of viral M(pro) and the PL(pro) proteases; convalescent plasma; and vaccine candidates. The Medline database was searched using combinations and variations of terms, including ‘Middle East respiratory syndrome coronavirus’, ‘MERS-CoV’, ‘SARS’, ‘therapy’, ‘molecular’, ‘vaccine’, ‘prophylactic’, ‘S protein’, ‘DPP4’, ‘heptad repeat’, ‘protease’, ‘inhibitor’, ‘anti-viral’, ‘broad-spectrum’, ‘interferon’, ‘convalescent plasma’, ‘lopinavir ritonavir’, ‘antibodies’, ‘antiviral peptides’ and ‘live attenuated viruses’. There are many options for the development of MERS-CoV-specific therapies. Currently, MERS-CoV is not considered to have pandemic potential. However, the high mortality rate and potential for mutations that could increase transmissibility give urgency to the search for direct, effective therapies. Well-designed and controlled clinical trials are needed, both for existing therapies and for prospective direct therapies.


id: cord-329514-dnh3rx0q
title: Middle Ear and Eustachian Tube
author: Kurono, Yuichi
date: 2007-05-09
txt: ./txt/cord-329514-dnh3rx0q.txt
cache: ./cache/cord-329514-dnh3rx0q.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780124915435500929
doi: 10.1016/b978-012491543-5/50092-9
abstract: nan
summary:
  Although specific IgG antibodies are protective against the invasion of bacterial antigen into the middle ear, some evidence suggests that systemic immune system may be involved in inducing or sustaining MEEs. Ueyama et al. The presence of antigen-specific IgA antibodies in MEEs of patients with AOM as well as OME suggests that the mucosal immune system in the middle ear plays a role in the pathogenesis of those diseases. (1996) also reported that parenteral immunization with P6 did not alter the extent or duration of nasopharyngeal colonization by NTHi. These results indicate that IgA antibodies in nasopharyngeal secretions inhibit the adherence of middle ear pathogens to nasopharyngeal mucosa and facilitate the clearance of those bacteria from the nasopharynx. Induction of specific immunoglobulin A and Th2 immune responses to P6 outer membrane protein of nontypeable Haemophilus influenzae in middle ear mucosa by intranasal immunization


id: cord-330343-p7a8chn4
title: An updated roadmap for MERS-CoV research and product development: focus on diagnostics
author: Kelly-Cirino, Cassandra
date: 2019-02-01
txt: ./txt/cord-330343-p7a8chn4.txt
cache: ./cache/cord-330343-p7a8chn4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1136/bmjgh-2018-001105
doi: 10.1136/bmjgh-2018-001105
summary:
  ► Diagnostic research and development (R&D) needs to include point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation.

abstract:
  Diagnostics play a central role in the early detection and control of outbreaks and can enable a more nuanced understanding of the disease kinetics and risk factors for the Middle East respiratory syndrome-coronavirus (MERS-CoV), one of the high-priority pathogens identified by the WHO. In this review we identified sources for molecular and serological diagnostic tests used in MERS-CoV detection, case management and outbreak investigations, as well as surveillance for humans and animals (camels), and summarised the performance of currently available tests, diagnostic needs, and associated challenges for diagnostic test development and implementation. A more detailed understanding of the kinetics of infection of MERS-CoV is needed in order to optimise the use of existing assays. Notably, MERS-CoV point-of-care tests are needed in order to optimise supportive care and to minimise transmission risk. However, for new test development, sourcing clinical material continues to be a major challenge to achieving assay validation. Harmonisation and standardisation of laboratory methods are essential for surveillance and for a rapid and effective international response to emerging diseases. Routine external quality assessment, along with well-characterised and up-to-date proficiency panels, would provide insight into MERS-CoV diagnostic performance worldwide. A defined set of Target Product Profiles for diagnostic technologies will be developed by WHO to address these gaps in MERS-CoV outbreak management.


id: cord-331228-wbd0s4fo
title: Middle East respiratory syndrome coronavirus: a comprehensive review
author: Shehata, Mahmoud M.
date: 2016-01-20
txt: ./txt/cord-331228-wbd0s4fo.txt
cache: ./cache/cord-331228-wbd0s4fo.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26791756/
doi: 10.1007/s11684-016-0430-6
summary:
  authors: Shehata, Mahmoud M.; Gomaa, Mokhtar R.; Ali, Mohamed A.; Kayali, Ghazi Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation Middle East respiratory syndrome coronavirus (MERS-CoV)-Saudi Arabia Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study First cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: a report of nosocomial transmission Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia

abstract:
  The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.


id: cord-332237-8oykgp0h
author: Omrani, Ali S
date: 2014-09-29
txt: ./txt/cord-332237-8oykgp0h.txt
cache: ./cache/cord-332237-8oykgp0h.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S147330991470920X
doi: 10.1016/s1473-3099(14)70920-x
summary:
  title: Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. INTERPRETATION: In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. 8 We aimed to assess outcomes of a treatment programme for patients with severe MERS-CoV infection that consisted of oral ribavirin and subcutaneous pegylated interferon alfa-2a. In critically ill patients with severe MERS-CoV infection, our study shows that ribavirin and pegylated interferon alfa-2a therapy is associated with a signifi cant 14-day survival benefi t compared with standard treatment. 18 In another report, 19 a patient with severe MERS-CoV infection received ribavirin and interferon therapy with good clinical response and no signifi cant adverse eff ects.

title:
  Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. METHODS: In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8–10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ(2) and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. FINDINGS: We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0–8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·054). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002). INTERPRETATION: In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended. FUNDING: None.


id: cord-332952-d5l60cgc
title: MERS: Progress on the global response, remaining challenges and the way forward
author: nan
date: 2018-09-17
txt: ./txt/cord-332952-d5l60cgc.txt
cache: ./cache/cord-332952-d5l60cgc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30236531/
doi: 10.1016/j.antiviral.2018.09.002
summary:
  Typical of an emerging zoonosis, Middle East respiratory syndrome coronavirus (MERS-CoV) has an animal reservoir, i.e. dromedary camels in which the virus causes little to no disease (Mohd et al., 2016) . For example, studies of respiratory pathogens (Yu et al., 2007; Tran et al., 2012; Thompson et al., 2013) and MERS-CoV conducted in the Middle East (Assiri et al., 2013; Oboho et al., 2015; Hunter et al., 2016; Balkhy et al., 2016) and the Republic of Korea (Bin et al., 2016; Kim et al., 2016a Kim et al., , 2016b Nam et al., 2017) illustrate that aerosol-generating procedures and non-invasive ventilation, combined with inappropriate infection prevention and control practices and lack of adherence to standard practices had an important role in facilitating human-to-human transmission in health care settings. The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study Sero-prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) specific antibodies in dromedary camels in Tabuk, Saudi Arabia

abstract:
  This article summarizes progress in research on Middle East Respiratory Syndrome (MERS) since a FAO-OIE-WHO Global Technical Meeting held at WHO Headquarters in Geneva on 25–27 September 2017. The meeting reviewed the latest scientific findings and identified and prioritized the global activities necessary to prevent, manage and control the disease. Critical needs for research and technical guidance identified during the meeting have been used to update the WHO R&D MERS-CoV Roadmap for diagnostics, therapeutics and vaccines and a broader public health research agenda. Since the 2017 meeting, progress has been made on several key actions in animal populations, at the animal/human interface and in human populations. This report also summarizes the latest scientific studies on MERS since 2017, including data from more than 50 research studies examining the presence of MERS-CoV infection in dromedary camels.


id: cord-337825-ujq9mxk7
title: Overview of lethal human coronaviruses
author: Chen, Bin
date: 2020-06-10
txt: ./txt/cord-337825-ujq9mxk7.txt
cache: ./cache/cord-337825-ujq9mxk7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41392-020-0190-2
doi: 10.1038/s41392-020-0190-2
summary:
  Coronaviruses are the largest +ssRNA viruses and contain at least 14 ORFs, 16 protein combines with viral RNA to form a nucleocapsid, which is involved in the replication of SARS-CoV and is the most abundant protein in virus-infected cells. MERS-CoV can infect T-cells from human lymphoid organs and causes the peripheral blood inducing apoptosis by intrinsic and extrinsic pathways, thus avoiding host immune response detection method, Nanopore Targeted Sequencing, also has the potential for efficiently detecting viruses in a reasonable time. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

abstract:
  Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus–host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.


id: cord-341795-zbqfs77n
author: Sikkema, R. S.
date: 2019-02-21
txt: ./txt/cord-341795-zbqfs77n.txt
cache: ./cache/cord-341795-zbqfs77n.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1017/s095026881800345x
doi: 10.1017/s095026881800345x
summary:
  This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. In the field surveys included in this review, MERS-CoV RNA has been described in rectal swab samples, although other field studies report negative results [3, [22] [23] [24] and when viral RNA can be detected, the positivity rate of rectal swabs is lower compared with nasal swab samples [19, [25] [26] [27] . Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study Longitudinal study of Middle East respiratory syndrome coronavirus infection in dromedary camel herds in Saudi Arabia Middle East respiratory syndrome coronavirus (MERS-CoV) RNA and neutralising antibodies in milk collected according to local customs from dromedary camels

title:
  Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review

abstract:
  Dromedary camels have been shown to be the main reservoir for human Middle East respiratory syndrome (MERS) infections. This systematic review aims to compile and analyse all published data on MERS-coronavirus (CoV) in the global camel population to provide an overview of current knowledge on the distribution, spread and risk factors of infections in dromedary camels. We included original research articles containing laboratory evidence of MERS-CoV infections in dromedary camels in the field from 2013 to April 2018. In general, camels only show minor clinical signs of disease after being infected with MERS-CoV. Serological evidence of MERS-CoV in camels has been found in 20 countries, with molecular evidence for virus circulation in 13 countries. The seroprevalence of MERS-CoV antibodies increases with age in camels, while the prevalence of viral shedding as determined by MERS-CoV RNA detection in nasal swabs decreases. In several studies, camels that were sampled at animal markets or quarantine facilities were seropositive more often than camels at farms as well as imported camels vs. locally bred camels. Some studies show a relatively higher seroprevalence and viral detection during the cooler winter months. Knowledge of the animal reservoir of MERS-CoV is essential to develop intervention and control measures to prevent human infections.


id: cord-343302-g9vcchrh
author: Agrawal, Anurodh Shankar
date: 2016-08-19
txt: ./txt/cord-343302-g9vcchrh.txt
cache: ./cache/cord-343302-g9vcchrh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/srep31629
doi: 10.1038/srep31629
summary:
  title: Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Here, we further characterized this novel human mAb in our Tg mouse model of MERS-CoV infection and showed prophylactic and therapeutic protection of mice treated with m336 before and after a lethal challenge with the virus, respectively. In our studies, we noted that passively transferred with 1 mg and 0.1 mg of m336 monoclonal antibodies to individual mice 12 h prior to challenge with 1,000 LD 50 of MERS-CoV resulted in 100% and 75% protection against lethality, respectively (Fig. 1) , suggesting that using 0.1 mg m336/mouse as a prophylaxis is suboptimal to completely neutralize viral infection, thereby allowing residual viruses to replicate within lungs during the course of infection.

title:
  Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection

abstract:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.


id: cord-345046-str19r9a
author: Al Ghamdi, Mohammed
date: 2016-04-21
txt: ./txt/cord-345046-str19r9a.txt
cache: ./cache/cord-345046-str19r9a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27097824/
doi: 10.1186/s12879-016-1492-4
summary:
  title: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia In this recent cohort, when comparing survivors to nonsurvivors, survival was associated with male gender, vomiting on admission, elevated respiratory rate, abnormal lung exam on physical exam, working as a healthcare worker, history of hypertension, elevated ALT, clearance of MERS CoV on repeat PCR testing, and receiving mycophenolate mofetil or beta interferon (Table 1 ). In analyzing the relationship between severity of illness and treatments administered, beta interferon and mycophenolate mofetil were given to less severely ill patients (Table 3) Discussion MERS-CoV is an emerging disease for which the initial epidemiology has been described, but in-depth clinical studies and the role of therapy in incompletely understood. We present data from a retrospective cohort of ill patients with Mers-CoV and the results of the evaluation of the clinical efficacy of beta interferon beta, alpha interferon, ribavirin and mycophenolate mofetil in addition to routine supportive care.

title:
  Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia

abstract:
  BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.


id: cord-345081-15s2i6f0
title: Middle East respiratory syndrome in children: Dental considerations
author: Al-Sehaibany, Fares S.
date: 2017-04-17
txt: ./txt/cord-345081-15s2i6f0.txt
cache: ./cache/cord-345081-15s2i6f0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.15537/smj.2017.4.15777
doi: 10.15537/smj.2017.4.15777
summary:
  As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. 1, 17 Viral infections, such as severe acute respiratory syndrome Saudi Med J 2017; Vol. 38 (4) www.smj.org.sa (SARS-CoV), may be transmitted to healthcare workers from infected patients through aerosols. 19 This review is an attempt to discuss MERS-CoV infection among children and those providing dental treatment to them, including precautions and considerations pertaining to the practice of pediatric dentistry. In pediatric dental practice, effective infection control measures for the prevention or minimization of viral infection transmission can be implemented by a) controlling the gag or cough reflex; b) reducing aerosol/ splatter generation; c) managing contaminated air and; d) improving personal protection.

abstract:
  As of January 2016, 1,633 laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and 587 MERS-related deaths have been reported by the World Health Organization globally. Middle East Respiratory Syndrome Coronavirus may occur sporadically in communities or may be transmitted within families or hospitals. The number of confirmed MERS-CoV cases among healthcare workers has been increasing. Middle East Respiratory Syndrome Coronavirus may also spread through aerosols generated during various dental treatments, resulting in transmission between patients and dentists. As MERS-CoV cases have also been reported among children, pediatric dentists are at risk of MERS-CoV infection. This review discusses MERS-CoV infection in children and healthcare workers, especially pediatric dentists, and considerations pertaining to pediatric dentistry. Although no cases of MERS-CoV transmission between a patient and a dentist have yet been reported, the risk of MERS-CoV transmission from an infected patient may be high due to the unique work environment of dentists (aerosol generation).


id: cord-345591-zwh1xj5u
author: Al-Dorzi, Hasan M.
date: 2016-10-24
url: https://www.ncbi.nlm.nih.gov/pubmed/27778310/
doi: 10.1186/s13613-016-0203-z
title:
  The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study

abstract:
  BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August–September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.


id: cord-349010-n4s8dzgp
title: Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
author: Al-Tawfiq, Jaffar A.
date: 2016-12-24
url: https://www.ncbi.nlm.nih.gov/pubmed/27937060/
doi: 10.1080/14787210.2017.1271712
abstract:
  Introduction: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an important emerging respiratory pathogen. MERS-CoV resulted in multiple hospital outbreaks within and outside the Arabian Peninsula. The disease has a high case fatality rate, with the need for a therapeutic option. Areas covered: In this review, we provide an overview of the progress in the development of therapeutic strategies for MERS. We searched PubMed, Embase, Cochrane, Scopus, and Google Scholar, using the following terms: ‘MERS’, ‘MERS-CoV’, ‘Middle East respiratory syndrome’ in combination with ‘treatment’ or ‘therapy’. Expert commentary: There are multiple agents tried in vitro and in vivo. None of these agents were used in large clinical studies. Available clinical studies are limited to the use of the combination of interferon and other agents. These clinical studies are based solely on case reports and case series. There are no prospective or randomized trials. There is a need to have prospective and randomized clinical trials for the therapy of MERS-CoV. However, this strategy might be hampered by the sporadic cases outside the large hospital outbreaks.


id: cord-349287-mwj2qby4
title: MERS coronavirus: diagnostics, epidemiology and transmission
author: Mackay, Ian M.
date: 2015-12-22
txt: ./txt/cord-349287-mwj2qby4.txt
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url: https://doi.org/10.1186/s12985-015-0439-5
doi: 10.1186/s12985-015-0439-5
summary:
  The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Since asymptomatic zoonoses have been posited [72] , an absence of antibodies to MERS-CoV among some humans who have regular and close contact with camels may reflect the rarity of actively infected animals at butcheries, a limited transmission risk associated with slaughtering DCs [70] , a pre-existing cross-protective immune status or some other factor(s) resulting in a low risk of disease and concurrent seroconversion developing after exposure in this group. First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-tohuman transmission

abstract:
  The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.


id: cord-349643-jtx7ni9b
title: Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus
author: Uyeki, Timothy M.
date: 2016-07-17
txt: ./txt/cord-349643-jtx7ni9b.txt
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mime: text/plain
url: https://doi.org/10.3201/eid2207.160022
doi: 10.3201/eid2207.160022
summary:
  Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. F rom September 2012 through April 27, 2016, a total of 1,728 laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infections, leading to 624 deaths (36% case-fatality proportion), had been reported to the World Health Organization (WHO) (1) . Prophylaxis with a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody protects rabbits from MERS-CoV infection

abstract:
  Preclinical development of and research on potential Middle East respiratory syndrome coronavirus (MERS-CoV) medical countermeasures remain preliminary; advancements are needed before most countermeasures are ready to be tested in human clinical trials. Research priorities include standardization of animal models and virus stocks for studying disease pathogenesis and efficacy of medical countermeasures; development of MERS-CoV diagnostics; improved access to nonhuman primates to support preclinical research; studies to better understand and control MERS-CoV disease, including vaccination studies in camels; and development of a standardized clinical trial protocol. Partnering with clinical trial networks in affected countries to evaluate safety and efficacy of investigational therapeutics will strengthen efforts to identify successful medical countermeasures.


id: cord-351186-llnlto7p
title: The first case of the 2015 Korean Middle East Respiratory Syndrome outbreak
author: Park, Yong-Shik
date: 2015-11-14
txt: ./txt/cord-351186-llnlto7p.txt
cache: ./cache/cord-351186-llnlto7p.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26725226/
doi: 10.4178/epih/e2015049
summary:
  Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments. Through personal and phone interviews we contacted employees at business facility in Saudi Arabia who may have had contact with Patient #1 during the incubation period; we investigated the places he visited, presence or absence of MERS symptoms in the individuals he contacted, history of visiting medical facilities in the Middle East, and history of consuming camel milk or meat, among other things.

abstract:
  This study reviewed problems in the prevention of outbreak and spread of Middle East Respiratory Syndrome (MERS) and aimed to provide assistance in establishing policies to prevent and manage future outbreaks of novel infectious diseases of foreign origin via in-depth epidemiological investigation of the patient who initiated the MERS outbreak in Korea, 2015. Personal and phone interviews were conducted with the patient and his guardians, and his activities in Saudi Arabia were investigated with the help of the Saudi Arabian Ministry of Health. Clinical courses and test results were confirmed from the medical records. The patient visited 4 medical facilities and contacted 742 people between May 11, 2015, at symptom onset, and May 20, at admission to the National Medical Center; 28 people were infected and diagnosed with MERS thereafter. Valuable lessons learned included: (1) epidemiological knowledge on the MERS transmission pattern and medical knowledge on its clinical course; (2) improvement of epidemiological investigative methods via closed-circuit television, global positioning system tracking, and review of Health Insurance Review and Assessment Service records; (3) problems revealed in the existing preventive techniques, including early determination of the various people contacted; (4) experiences with preventive methods used for the first time in Korea, including cohort quarantine; (5) reconsideration of the management systems for infectious disease outbreaks across the country, such as this case, at the levels of central government, local government, and the public; (6) reconsideration of hospital infectious disease management systems, culture involving patient visitation, and emergency room environments.


id: cord-352527-eeyqh9nc
title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain
author: Zhou, Yusen
date: 2019-01-14
txt: ./txt/cord-352527-eeyqh9nc.txt
cache: ./cache/cord-352527-eeyqh9nc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30646569/
doi: 10.3390/v11010060
summary:
  A number of MERS vaccines have been developed based on viral RBD, including nanoparticles, virus-like particles (VLPs), and recombinant proteins, and their protective efficacy has been evaluated in animal models, including mice with adenovirus 5 (Ad5)-directed expression of human DPP4 (Ad5/hDPP4), hDPP4-transgenic (hDPP4-Tg) mice, and non-human primates (NHPs) [88] [89] [90] [91] [92] [93] [94] . Receptor usage of a novel bat lineage C Betacoronavirus reveals evolution of Middle East respiratory syndrome-related coronavirus spike proteins for human dipeptidyl peptidase 4 binding Recombinant receptor-binding domains of multiple Middle East respiratory syndrome coronaviruses (MERS-CoVs) induce cross-neutralizing antibodies against divergent human and camel MERS-CoVs and antibody escape mutants A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A novel nanobody targeting Middle East respiratory syndrome coronavirus (MERS-CoV) receptor-binding domain has potent cross-neutralizing activity and protective efficacy against MERS-CoV

abstract:
  Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.


id: cord-354302-l2kywzro
title: Replication and Shedding of MERS-CoV in Upper Respiratory Tract of Inoculated Dromedary Camels
author: Adney, Danielle R.
date: 2014-12-17
txt: ./txt/cord-354302-l2kywzro.txt
cache: ./cache/cord-354302-l2kywzro.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3201/eid2012.141280
doi: 10.3201/eid2012.141280
summary:
  Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. T he Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 related to a fatal human case of pneumonia in Saudi Arabia (1) . MERS-CoV shedding started during 1-2 dpi, as detected by the presence of infectious virus and viral RNA by qPCR in nasal swab samples. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels

abstract:
  In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.


