Middle East Respiratory Syndrome Coronavirus Infection Research Articles

Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism

Middle East respiratory syndrome coronavirus (MERS-CoV) infects humans from zoonotic sources and causes severe pulmonary disease. Virions require spike (S) glycoproteins for binding to cell receptors and for catalyzing virus-cell membrane fusion. Fusion occurs only after S proteins are cleaved sequentially, first during their secretion through the exocytic organelles of virus-producing cells, and second after virus binding to target-cell receptors. To more precisely determine how sequential proteolysis contributes to CoV infection, we introduced S mutations obstructing the first cleavages. These mutations severely compromised MERS-CoV infection into human lung-derived cells, but had little effect on infection into several other cell types. These cell type-specific requirements for proteolysis correlated with S conformations during cell entry. Without the first cleavages, S proteins resisted cell receptor-induced conformational changes, which restricted the second, fusion-activating cleavages. Consistent with these findings, precleaved MERS viruses used receptor-proximal, cell-surface proteases to effect the second fusion-activating cleavages during cell entry, whereas the more rigid uncleaved MERS viruses trafficked past these cell-surface proteases and into endosomes. Uncleaved viruses were less infectious to human airway epithelial and Calu3 cell cultures because they lacked sufficient endosomal fusion-activating proteases. Thus, by sensitizing viruses to receptor-induced conformational changes, the first S cleavages expand virus tropism to cell types that are relevant to lung infection, and therefore may be significant determinants of MERS-CoV virulence.

MERS-CoV at the Animal-Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation.

Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels–camels, camels–human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated “most likely” incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal–human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak perceptions of risk and stress evaluation in nurses.

Saudi Arabia was affected by an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV). We aimed to determine the perception of risk and level of stress among nurses. A questionnaire survey was administered to determine the perceptions of risk of MERS-CoV infection. The majority of the participants were females (332; 86.0%), and there were 54 (14.0%) males. Of the 386 respondents, nurses constituted the majority of the respondents (293; 75.9%), and there were 34 doctors (8.8%). The percentage of exposure was found to be greater in those who were working in the intensive care unit (ICU) (89; 23%). There was a significant difference in the worry and fear scale of contracting the MERS-CoV infection between participants who worked in isolation areas, ICUs, and emergency rooms (mean: 3.01±1.1) compared to participants who worked in areas that are less likely to admit and have MERS-CoV suspected or positive cases (mean: 2.77±1.1; p = 0.031. Females were significantly more worried and fearful of contracting the virus compared to males (mean: 2.92±1.1 versus 2.61±1.0, respectively; p = 0.045). MERS-CoV caused a relatively significant level of distress among nurses. There was a difference in the worry and fear scale of contracting the MERS-CoV infection between participants who worked in areas likely to admit and have MERS-CoV suspected or positive cases. After the campaign, the level of confidence got higher and the participants were more adherent to the infection control precautions.

Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.

Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus.

The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface. Infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with the highest mortality rate among all known human-pathogenic coronaviruses. Currently, there are no approved vaccines or therapeutics against MERS-CoV infection. The identification of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV advanced our knowledge on the cell binding biology of MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by functioning as an attachment factor. In this regard, CEACAM5 could serve as a novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of antiviral strategies for MERS-CoV.

Middle East Respiratory Syndrome Coronavirus Transmission in Extended Family, Saudi Arabia, 2014.

Risk factors for human-to-human transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) are largely unknown. After MERS-CoV infections occurred in an extended family in Saudi Arabia in 2014, relatives were tested by using real-time reverse transcription PCR (rRT-PCR) and serologic methods. Among 79 relatives, 19 (24%) were MERS-CoV positive; 11 were hospitalized, and 2 died. Eleven (58%) tested positive by rRT-PCR; 8 (42%) tested negative by rRT-PCR but positive by serology. Compared with MERS-CoV-negative adult relatives, MERS-CoV-positive adult relatives were older and more likely to be male and to have chronic medical conditions. Risk factors for household transmission included sleeping in an index patient's room and touching respiratory secretions from an index patient. Casual contact and simple proximity were not associated with transmission. Serology was more sensitive than standard rRT-PCR for identifying infected relatives, highlighting the value of including serology in future investigations.

Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.

The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.

Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin

Highly pathogenic human coronaviruses associated with a severe respiratory syndrome, including Middle East respiratory syndrome coronavirus (MERS-CoV), have recently emerged. The MERS-CoV epidemic started in 2012 and is still ongoing, with a mortality rate of approximately 35%. No vaccine is available against MERS-CoV and therapeutic options for MERS-CoV infections are limited to palliative and supportive care. A search for specific antiviral treatments is urgently needed. Coronaviruses are enveloped viruses, with the spike proteins present on their surface responsible for virus entry into the target cell. Lectins are attractive anti-coronavirus candidates because of the highly glycosylated nature of the spike protein. We tested the antiviral effect of griffithsin (GRFT), a lectin isolated from the red marine alga Griffithsia sp. against MERS-CoV infection. Our results demonstrate that while displaying no significant cytotoxicity, griffithsin is a potent inhibitor of MERS-CoV infection. Griffithsin also inhibits entry into host cells of particles pseudotyped with the MERS-CoV spike protein, suggesting that griffithsin inhibits spike protein function during entry. Spike proteins have a dual function during entry, they mediate binding to the host cell surface and also the fusion of the viral envelope with host cell membrane. Time course experiments show that griffithsin inhibits MERS-CoV infection at the binding step. In conclusion, we identify griffithsin as a potent inhibitor of MERS-CoV infection at the entry step.

Super-spreading events of MERS-CoV infection

Super-spreading events of MERS-CoV infection

MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study

BackgroundIn 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital.MethodsWe identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission.Findings675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4–8] vs 11 days [6–12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure.InterpretationOur results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases.FundingNone.

Response to Emergence of Middle East Respiratory Syndrome Coronavirus, Abu Dhabi, United Arab Emirates, 2013-2014.

In January 2013, several months after Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia, Abu Dhabi, United Arab Emirates, began surveillance for MERS-CoV. We analyzed medical chart and laboratory data collected by the Health Authority-Abu Dhabi during January 2013-May 2014. Using real-time reverse transcription PCR, we tested respiratory tract samples for MERS-CoV and identified 65 case-patients. Of these patients, 23 (35%) were asymptomatic at the time of testing, and 4 (6%) showed positive test results for >3 weeks (1 had severe symptoms and 3 had mild symptoms). We also identified 6 clusters of MERS-CoV cases. This report highlights the potential for virus shedding by mildly ill and asymptomatic case-patients. These findings will be useful for MERS-CoV management and infection prevention strategies.

Epidemiological investigation of Middle East respiratory syndrome coronavirus in dromedary camel farms linked with human infection in Abu Dhabi Emirate, United Arab Emirates.

The objective of this research was to investigate the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection primarily in dromedary camel farms and the relationship of those infections with infections in humans in the Emirate of Abu Dhabi. Nasal swabs from 1113 dromedary camels (39 farms) and 34 sheep (1 farm) and sputum samples from 2 MERS-CoV-infected camel farm owners and 1 MERS-CoV-infected sheep farm owner were collected. Samples from camels and humans underwent real-time reverse-transcription quantitative PCR screening to detect MERS-CoV. In addition, sequencing and phylogenetic analysis of partially characterized MERS-CoV genome fragments obtained from camels were performed. Among the 40 farms, 6 camel farms were positive for MERS-CoV; the virus was not detected in the single sheep farm. The maximum duration of viral shedding from infected camels was 2 weeks after the first positive test result as detected in nasal swabs and in rectal swabs obtained from infected calves. Three partial camel sequences characterized in this study (open reading frames 1a and 1ab, Spike1, Spike2, and ORF4b) together with the corresponding regions of previously reported MERS-CoV sequence obtained from one farm owner were clustering together within the larger MERS-CoV sequences cluster containing human and camel isolates reported for the Arabian Peninsula. Data provided further evidence of the zoonotic potential of MERS-CoV infection and strongly suggested that camels may have a role in the transmission of the virus to humans.

Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with life-threatening severe illnesses and a mortality rate of approximately 35%, particularly in patients with underlying comorbidities. A systematic analysis of 637 MERS-CoV cases suggests that diabetes and hypertension are equally prevalent in approximately 50% of the patients. Cardiac diseases are present in 30% and obesity in 16% of the cases. These conditions down-regulate the synthesis of proinflammatory cytokines and impair the host's innate and humoral immune systems. In conclusion, protection against MERS-CoV and other respiratory infections can be improved if public health vaccination strategies are tailored to target persons with chronic disorders.

Development of Dual TaqMan Based One-Step rRT-PCR Assay Panel for Rapid and Accurate Diagnostic Test of MERS-CoV: A Novel Human Coronavirus, Ahead of Hajj Pilgrimage.

BackgroundCoronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV.ObjectivesIn this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO).Materials and MethodsIn this experimental study, acquiring patient samples was difficult; thus, according to WHO recommendations and standard protocols, we synthesized RNA sequences of upE and ORF1b genes as the template signatures and TaqMan based-diagnostic rRT-PCR assays were carried out using these synthetic genes for detection of MERS-CoV. In this research, we also inaugurated a cell-free system to transcribe these RNA sequences using the DNA templates synthesized.ResultsThe upE and ORF1b based one-step rRT-PCR assays were optimized by testing several times via different synthetic RNAs, and validation results were highly successful. The sensitivity obtained for upE was fewer than ten copies of RNA template per reaction and for ORF1b was 50 or fewer copies per reaction.ConclusionsThis study showed that the developed rRT-PCR assays are rapid, reliable, reproducible, specific, sensitive, and simple tools for detection of MERS-CoV. Finally, a kit consisting of two assay signatures and controls was assembled, which can be distributed to public health laboratories in Iran to support international MERS-CoV surveillance and public health response.

Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.

MERS-CoV Antibodies in Humans, Africa, 2013-2014.

Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.

Assessment of the risk posed to Singapore by the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea.

To assess the public health risk to Singapore posed by the Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea in 2015. The likelihood of importation of MERS cases and the magnitude of the public health impact in Singapore were assessed to determine overall risk. Literature on the epidemiology and contextual factors associated with MERS coronavirus infection was collected and reviewed. Connectivity between the Republic of Korea and Singapore was analysed. Public health measures implemented by the two countries were reviewed. The epidemiology of the 2015 MERS outbreak in the Republic of Korea remained similar to the MERS outbreaks in Saudi Arabia. In addition, strong infection control and response measures were effective in controlling the outbreak. In view of the air traffic between Singapore and MERS-affected areas, importation of MERS cases into Singapore is possible. Nonetheless, the risk of a serious public health impact to Singapore in the event of an imported case of MERS would be mitigated by its strong health-care system and established infection control practices. The MERS outbreak was sparked by an exported case from the Middle East, which remains a concern as the reservoir of infection (thought to be camels) continues to exist in the Middle East, and sporadic cases in the community and outbreaks in health-care settings continue to occur there. This risk assessment highlights the need for Singapore to stay vigilant and to continue enhancing core public health capacities to detect and respond to MERS coronavirus.

Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients.

BackgroundMiddle 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.MethodsRetrospective 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.ResultsDuring 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).ConclusionsMERS-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 materialThe online version of this article (doi:10.1186/s13054-016-1303-8) contains supplementary material, which is available to authorized users.

Middle East respiratory syndrome coronavirus: review of the current situation in the world.

This article reviews the current epidemiology and clinical presentation of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection and describes the preparedness plan of several countries. The MERS-CoV was first reported in 2012 and has since infected more than 1600 patients in 26 countries, mostly in Saudi Arabia and the Middle East. The epidemiology of the infection is compatible with multiple introductions of the virus into humans from an animal reservoir, probably dromedary camels. The clinical presentation ranges from no symptoms to severe pneumonitis and respiratory failure. Most confirmed cases so far were part of MERS-CoV clusters in hospital settings, affecting mainly middle-aged men and patients with a chronic disease or immuno-suppressed status. There is no vaccine or anti-viral medication available. Viral epidemics can occur anywhere in today’s “global village”. MERS-CoV is a relatively new virus, and this work is intended to add to the still-sparse data on its epidemiology, modes of transmission, natural history, and clinical features as well as to describe the preparedness plan for MERS-CoV infection in several countries. Effective national and international preparedness plans are essential to predict and control outbreaks, improve patient management, and ensure global health security.