Middle East Respiratory Syndrome Coronavirus Disease Research Articles

Knowledge, attitude, and practice study of Middle East respiratory syndrome Coronavirus in Oman

Background: In the 21st century, there has been an increase in the spread of various diseases. Middle East respiratory syndrome Coronavirus (MERS-CoV) disease is one of them. In order to contain and eradicate the spread of MERS-CoV, assessing public knowledge, attitude, and practice is important. This public study was conducted in the eleven governorates of Oman for its assessment. Methods: A national level cross-sectional survey was conducted online for a period of nine days using a questionnaire that contained forty-one questions. The questions were designed to evaluate public perception and understanding of MERS-CoV disease. The acquired data were analysed using SPSS software. Results: A total of 505 people participated in the survey. The majority of the participants were males from the Muscat region (46%). The ages of the participants were between <20 to 60 years. The survey revealed that 60% of the participants were unaware about the disease (p<0.001) and about 48% (p=0.003) of them were unsure about the symptoms of the disease. Most people had a positive attitude towards preventing the spread of the infection. Adherence to precautionary measures was higher among the female participants (69%, p=0.021). Primary information source for the public was through social media. Conclusions: Overall, the surveyed population had a varied perspective about the disease and fair knowledge on the preventive measures. However, a large percentage of the participants were unclear about the epidemic situation and lacked knowledge on the disease, but showed a positive attitude towards curbing the spread of infection.

Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality.

The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein–protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-021-01061-z.

Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries.

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

A global treatments for coronaviruses including COVID-19.

In late December 2019 in Wuhan, China, several patients with viral pneumonia were identified as 2019 novel coronavirus (2019‐nCoV). So far, there are no specific treatments for patients with coronavirus disease‐19 (COVID‐19), and the treatments available today are based on previous experience with similar viruses such as severe acute respiratory syndrome‐related coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), and Influenza virus. In this article, we have tried to reach a therapeutic window of drugs available to patients with COVID‐19. Cathepsin L is required for entry of the 2019‐nCoV virus into the cell as target teicoplanin inhibits virus replication. Angiotensin‐converting‐enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. In patients with COVID‐19, hydroxychloroquine decreases the inflammatory response and cytokine storm, but overdose causes toxicity and mortality. Neuraminidase inhibitors such as oseltamivir, peramivir, and zanamivir are invalid for 2019‐nCoV and are not recommended for treatment but protease inhibitors such as lopinavir/ritonavir (LPV/r) inhibit the progression of MERS‐CoV disease and can be useful for patients of COVID‐19 and, in combination with Arbidol, has a direct antiviral effect on early replication of SARS‐CoV. Ribavirin reduces hemoglobin concentrations in respiratory patients, and remdesivir improves respiratory symptoms. Use of ribavirin in combination with LPV/r in patients with SARS‐CoV reduces acute respiratory distress syndrome and mortality, which has a significant protective effect with the addition of corticosteroids. Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID‐19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.

The global burden of premature mortality due to the Middle East respiratory syndrome (MERS) using standard expected years of life lost, 2012 to 2019

BackgroundIt has been 8 years since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was reported in Saudi Arabia and the disease is still being reported in 27 countries; however, there is no international study to estimate the overall burden related of this emerging infectious disease. The present study was conducted to assess the burden of premature mortality due to Middle East respiratory syndrome (MERS) worldwide.MethodsIn this retrospective analysis, we have utilized publicly available data from the WHO website related to 1789 MERS patients reported between September 23, 2012 and May 17, 2019. To calculate the standard expected years of life lost (SEYLL), life expectancy at birth was set according to the 2000 global burden of disease study on levels 25 and 26 of West model life tables from Coale-Demeny at 82.5 and 80 years for females and males, respectively.ResultsOverall, the total SEYLL in males and females was 10,702 and 3817.5 years, respectively. The MERS patients within the age range of 30–59 year-olds had the highest SEYLL (8305.5 years) in comparison to the patients within the age groups 0–29 (SEYLL = 3744.5 years) and ≥ 60 years (SEYLL = 2466.5 years). The total SEYLL in all age groups in 2012, 2013, 2014, 2015, 2016, 2017, 2018, and 2019 were 71.5, 2006.5, 3162, 4425.5, 1809.5, 878, 1257.5 and 909 years, respectively. The most SEYLL related to MERS-CoV infection was in the early four years of the onset of the pandemic (2012 to 2015) and in the last four years of the MERS-CoV pandemic (216 to 2019), a significant reduction was observed in the SEYLL related to MERS-CoV infection in the MERS patients.ConclusionWe believe that the findings of this study will shed light about the burden of premature mortality due to MERS infection in the world and the results may provide necessary information for policy-makers to prevent, control, and make a quick response to the outbreak of MERS-CoV disease.

A recombinant VSV-vectored MERS-CoV vaccine induces neutralizing antibody and T cell responses in rhesus monkeys after single dose immunization

Middle East respiratory syndrome coronavirus (MERS-CoV) has been a highly threatening zoonotic pathogen since its outbreak in 2012. Similar to SARS-CoV, MERS-CoV belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the World Health Organization. Spike (S) protein of MERS-CoV is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. Here we constructed a chimeric virus based on the vesicular stomatitis virus (VSV) in which the G gene was replaced by MERS-CoV S gene (VSVΔG-MERS). The S protein efficiently incorporated into the viral envelope and mediated cell entry through binding its receptor, human DPP4. Knockdown of clathrin expression by siRNA drastically abrogated the infection of VSVΔG-MERS in Vero cells. Furthermore, in animal studies, the recombinant virus induced neutralizing antibodies and T cell responses in rhesus monkeys after a single intramuscular or intranasal immunization dose. Our findings indicate the potential of the chimeric VSVΔG-MERS as a rapid response vaccine candidate against emerging MERS-CoV disease.

MERS-CoV infection: Mind the public knowledge gap.

In August 2015, the Corona outbreak caused by Middle East respiratory syndrome coronavirus (MERS-CoV) was the 9th episode since June 2012 in Saudi Arabia. Little is known about the public awareness toward the nature or prevention of the disease. The aim of this work was to assess the knowledge of the adult population in Riyadh toward the MERS-CoV.In this cross-sectional survey, a self-administrated questionnaire was distributed to randomly selected participants visiting malls in Riyadh. The questionnaire contained measurable epidemiological and clinical MERS-CoV knowledge level variables and relevant source of information.The study included 676 participants. Mean age was 32.5 (±SD 8.6) years and 353 (47.8%) were males. Almost all participants heard about the corona disease and causative agent. The study showed a fair overall knowledge (66.0%), less knowledge on epidemiological features of the disease (58.3%), and good knowledge (90.7%) on the clinical manifestation of the MERS-CoV. Internet was the major (89.0%) source of disease information, and other sources including health care providers, SMS, television, magazines and books were low rated (all <25%). In a multivariate logistic regression analysis age ≤30 years (Odds Ratio (OR) = 1.647, 95%CI 1.048–2.584, P = 0.030), male gender (OR = 1.536, 95%CI 1.105–2.134, P = 0.01), and no tertiary education (OR = 1.957, 95%CI 1.264–3.030, P = 0.003) were independent significant predictors of poor epidemiological knowledge.This study concludes that there was inadequate epidemiological knowledge received by the public and the reliance mostly on the clinical manifestations to recognizing the MERS-CoV disease. Comprehensive public health education programs is important to increase awareness of simple epidemiological determinants of the disease is warranted.

MERS PUI Surveillance and Restrospective Identification in ESSENCE-FL, 2013-2015

ObjectiveTo retrospectively identify initial emergency department (ED)and urgent care center (UCC) visits for Florida’s Middle Eastrespiratory syndrome coronavirus disease (MERS-CoV) patientsunder investigation (PUIs) in the Florida Department of Health’s(DOH) syndromic surveillance system, the Electronic SurveillanceSystem for the Early Notification of Community-based Epidemics(ESSENCE-FL), using information gathered from PUI case reportforms and corresponding medical records for the purpose ofimproving syndromic surveillance for MERS-CoV. The results ofthis study may be further utilized in an effort to evaluate the currentMERS-CoV surveillance query.IntroductionHuman MERS-CoV was first reported in September 2012. Globally,all reported cases have been linked through travel to or residence inthe Arabian Peninsula with the exception of cases associated with anoutbreak involving multiple health care facilities in the Republic ofKorea ending in July 2015. While the majority of MERS-CoV caseshave been reported in the Arabian Peninsula, several cases have beenreported outside of the region. Most cases are believed to have beenacquired in the Middle East and then exported elsewhere, with no orrare instances of secondary transmission. Two cases of MERS-CoVwere exported to the United States and identified in May 2014. Oneof these cases traveled from Saudi Arabia to Florida.DOH conducts regular surveillance for MERS-CoV through theinvestigation of persons with known risk factors. PUIs have mostoften been identified by physicians reporting directly to local healthdepartments and by DOH staff regularly querying ED and UCC chiefcomplaint data in ESSENCE-FL. ESSENCE-FL currently capturesdata from 265 EDs and UCCs statewide and has been useful inidentifying cases associated with reportable disease and emergingpathogens.MethodsFrom 2013-2015 DOH identified and investigated 62 suspectedcases of MERS-CoV, including one confirmed case in May 2014.Specimens were collected from all 62 patients under investigation(PUIs) and 61 were ruled out. Of the 61 PUIs who were ruled out,ten were part of the contact investigation initiated following theidentification of MERS-CoV in May 2014 and were not included inthis analysis. DOH utilizes a MERS-CoV PUI case report form tocollect data regarding demographics, clinical presentation, and riskfactors. Retrospectively, additional documents including medicalrecords and discharge summaries were gathered and utilized toevaluate PUIs identified in ESSENCE-FL.Name of the facility where PUIs presented, date and time of visit,age at event, and sex were identified using PUI case report forms andcorresponding medical records and discharge summaries. Visit detailsfor each of the identified facilities were queried in ESSENCE-FLand pulled for all visits with corresponding age at event and sex forthe patient’s visit date. Additional PUI information including chiefcomplaint, discharge diagnosis, ZIP code, race, and ethnicity weregathered for the purpose of matching corresponding ESSENCE-FLdata fields. ESSENCE-FL visit details were narrowed by ZIP code (orlack of ZIP code for residents of other countries) and match detailswere recorded and evaluated. The fields examined were not alwayscomplete in ESSENCE-FL. Visits were considered matches when allavailable data in the fields examined were consistent with informationobtained in the PUI case report form and available medical recordsand discharge summaries.ResultsOf the 52 PUIs included in this analysis, 39 sought treatmentat facilities participating in ESSENCE-FL at their time of visit.Comparing information obtained from PUI documents with dataprovided in ESSENCE-FL, 30 ED visits were successfully matchedto PUIs, including an initial ED visit for the patient with a confirmedcase of MERS-CoV.ConclusionsFollowing preliminary identification, all matches are to beconfirmed with the appropriate hospitals. Future work to examine thechief complaints associated with patients’ initial ED visits identifiedin ESSENCE-FL will serve as a way to validate and improve uponthe query currently being used as a surveillance tool for MERS-CoV.Detailing these methods also has value in the replication of thisstudy for other diseases and in the development and validation ofother disease-specific queries. Summarizing the reasons why PUIswere unable to be matched to ESSENCE-FL visits is also useful inimproving system robustness.

Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus.

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.

Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.

An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.

Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.

Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.

206: Transcriptional signatures of pathogenesis and successful type I interferon and ribavirin therapy in a rhesus macaque model of MERS-CoV infection

A novel betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), emerged on the Arabian Peninsula in 2012. MERS-CoV was found to produce severe respiratory illness with case-fatality rates near 50%, and may be transmitted person-to-person in instances of close physical contact, such as among family members and to health care workers. As mice, hamsters, ferrets, and cynomolgus macaques are either not susceptible to MERS-CoV infection or do not develop observable clinical disease, we sought to determine whether rhesus macaques (Macaca mulatta) can be used as a model of MERS-CoV infection and disease. Animals challenged with MERS-CoV via multiple combined infection routes rapidly developed pneumonia, and we observed other clinical signs of illness, virus shedding, and virus replication in respiratory tissues. Using microarrays to compare transcripts associated with histopathologic lesions removed from the lungs of infected animals, we identified 173 significant differentially expressed genes (DEG) associated with lung lesions on day 3 post-infection concurrent with peak clinical signs. Functional analysis indicated that these genes were predominantly associated with proinflammatory processes, recruitment and chemotaxis of inflammatory cells, and antiviral immunity. Using singular value decomposition coupled multidimensional scaling (SVD-MDS), we also identified changes in similar inflammatory genes in peripheral blood mononuclear cells, suggesting a rapid activation of innate immune and inflammatory processes in leukocytes after infection. These data were consistent with cytokine and chemokine profiles in the blood of animals.Due to the urgent need for an effective therapeutic means of treating MERS-CoV patients, we used this rhesus macaque model to evaluate post-exposure treatment with combination interferon (IFN)-a2b and ribavirin (RBV), and identified key transcriptional signatures associated with disease severity and treatment efficacy. Animals treated with IFN-a2b/RBV beginning 8 h post-infection did not develop significant clinical or severe histopathologic signs of disease, breathing abnormalities, or radiographic evidence of pneumonia, and showed reduced viral loads and lower levels of serum proinflammatory cytokines. Microarray analysis of treated animals showed significant induction of interferon-stimulated genes (ISGs) and fewer upregulated transcripts associated with inflammatory processes. Additionally, we identified a subset of statistically significant DEGs associated with signaling pathways such as hedgehog, which has been linked to airway function and protection against pulmonary injury. Together, these data indicate that treatment of MERS-CoV-infected rhesus macaques with IFN-a2b and ribavirin reduces virus replication and improves clinical outcome, and suggests a transcriptomic basis for therapeutic efficacy. As these two drugs are already used together in the clinic, IFN-a2b and ribavirin may be useful for therapeutic intervention and patient management of new human MERS-CoV cases.

Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

BackgroundHuman infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital.MethodsPatient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV.FindingsInitial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure.InterpretationPatients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.FundingFrench Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.

Rhodopsin mutations in a Scottish retinitis pigmentosa population, including a novel splice site mutation in intron four.

Retinitis pigmentosa (RP) is the name given to a group of disorders, both clinically and genetically heterogeneous, that primarily affect the photoreceptor function of the eye. Mutations in the genes encoding for rhodopsin, RDS-peripherin, or the beta subunit of the cGMP phosphodiesterase enzyme can be responsible for the phenotype. In this study the rhodopsin gene has been screened for mutations in a panel of RP individuals and five different sequence changes have been detected to date in three dominantly inherited and two unclassified families. One of these, a base substitution in the 3'UTR, has not yet been confirmed as disease specific, while three missense substitutions have previously been reported and are likely to be responsible for the phenotype. The fifth change, a base substitution at the intron 4 acceptor splice site, represents a novel mutation and is assumed to be the causative mutation.