Middle East Respiratory Syndrome Patients Research Articles

Association of KIR Genes with Middle East Respiratory Syndrome Coronavirus Infection in South Koreans.

Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans. KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes. KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group (p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases. Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

Global concerns about camel flu: outbreak, etiology, genomic structure, transmission, symptoms, diagnostic tests, prevention, and treatment - correspondence.

Global concerns about camel flu: outbreak, etiology, genomic structure, transmission, symptoms, diagnostic tests, prevention, and treatment - correspondence.

Ribavirin plus Interferon or Oseltamivir in Severe Middle East Respiratory Syndrome Infection

Background: Middle East respiratory syndrome (MERS) is associated with significant mortality with no approved antiviral therapy. Objectives: The aim of this study was to compare the efficacy and safety of the combination of ribavirin and PEG-interferon α-2a (RIF), oseltamivir, and supportive care (SC) alone in MERS patients. Materials and Methods: Retrospective cohort for all patients admitted to the intensive care unit with severe symptomatic laboratory-confirmed MERS infection between September 2013 and February 2017. Patients were divided into two pairwise comparisons: RIF and oseltamivir combined (antivirals) vs. SC; and RIF vs. oseltamivir. The primary endpoint was 60-day mortality. Secondary endpoints were the requirement for mechanical ventilation (MV) and renal replacement therapy (RRT), and laboratory changes. Results: A total of 113 patients met the study inclusion criteria; 77 received antivirals (47 received RIF and 30 oseltamivir), and 36 SC. The 60-day mortality rate was 36% with antivirals vs. 50% with SC (P = 0.136), and 45% with RIF vs. 23% with oseltamivir (P = 0.092). The MV requirement was 42% with antivirals vs. 65% with SC (P = 0.083), and 54% with RIF vs. 27% with oseltamivir (P = 0.067). The RRT requirement was 29% with antivirals vs. 31% with SC (P = 0.943), and 40% with RIF vs. 14% with oseltamivir (P = 0.019). The median hemoglobin decrease with RIF was 4 g/dL vs. 1 with oseltamivir (P < 0.001); the WBC decrease with RIF was 1.3 vs. 0.2 with oseltamivir (P = 0.007); the blood glucose increase with RIF was 143 mg/dL vs. 89 with oseltamivir (P = 0.036), and the indirect bilirubin increase with RIF was 0.4 mg/dL vs. 0.3 with oseltamivir (P = 0.023). Conclusions: In this study, the use of RIF or oseltamivir in severe MERS infections did not significantly reduce 60-day mortality, nor the requirement for MV or RRT. Furthermore, the subgroup that received oseltamivir had more favorable renal, hepatic, and hematological outcomes than RIF. Larger, prospective, well-designed studies are warranted to confirm these findings.

Kinetics of antibody response in critically ill patients with Middle East respiratory syndrome and association with mortality and viral clearance

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1–3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.

Spatiotemporal behaviors of the ridership of a public transportation system during an epidemic outbreak: case of MERS in Seoul.

During May and June 2015, an outbreak of the Middle East respiratory syndrome (MERS) occurred in Korea, which raised the fear of contagion throughout society and suppressed the use of public transportation systems. Exploring daily ridership data of the Seoul bus transportation system, along with the number of infected patients and search volume in web portals, we observe that ridership decreased abruptly while attention was heavily focused online. Then this temporal reduction recovered exponentially with a characteristic time of 3 weeks when newly confirmed cases began to decrease. We also find with the data of ranked keywords of web portals that areas with severely reduced ridership tended to cluster and spatiotemporal variations of such clusters were highly associated with general hospitals where MERS patients were treated. On the other hand, the spatial reduction in ridership relaxed algebraically with the distance from a general hospital while the outbreak was severe. We further probe the influence of the epidemic outbreak in the framework of linear response theory, which relates the responses to the epidemic outbreak (“perturbation”) with correlations in the absence of the perturbation. Indeed, the spatial correlation function of the ridership changes is observed to follow a power law, sharing the same exponent as the spatial relaxation of the response function. This new theoretical approach offers a useful tool for understanding responses of public transportation system to epidemic or accidental disasters.

Comparison of characteristics and ventilatory course between coronavirus disease 2019 and Middle East respiratory syndrome patients with acute respiratory distress syndrome.

Background Both coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) can cause acute respiratory distress syndrome (ARDS); however, their ARDS course and characteristics have not been compared, which we evaluate in our study.Methods MERS patients with ARDS seen during the 2014 outbreak and COVID-19 patients with ARDS admitted between March and December 2020 in our hospital were included, and their clinical characteristics, ventilatory course, and outcomes were compared.Results Forty-nine and 14 patients met the inclusion criteria for ARDS in the COVID-19 and MERS groups, respectively. Both groups had a median of four comorbidities with high Charlson comorbidity index value of 5 points (P>0.22). COVID-19 patients were older, obese, had significantly higher initial C-reactive protein (CRP), more likely to get trial of high-flow oxygen, and had delayed intubation (P≤0.04). The postintubation course was similar between the groups. Patients in both groups experienced a prolonged duration of mechanical ventilation, and majority received paralytics, dialysis, and vasopressor agents (P>0.28). The respiratory and ventilatory parameters after intubation (including tidal volume, fraction of inspired oxygen, peak and plateau pressures) and their progression over 3 weeks were similar (P>0.05). Rates of mortality in the ICU (53% vs. 64%) and hospital (59% vs. 64%) among COVID-19 and MERS patients (P≥0.54) were very high.Conclusions Despite some distinctive differences between COVID-19 and MERS patients prior to intubation, the respiratory and ventilatory parameters postintubation were not different. The higher initial CRP level in COVID-19 patients may explain the steroid responsiveness in this population.

Current View on Convalescent Plasma Therapy for COVID-19 Treatment: A Systematic Review and Prospective Meta-Analysis Based on Previous Respiratory Pandemics

Introduction: In addition to antiviral medication, Convalescent plasma therapy (CPT) has also been investigated for COVID-19 treatment. This study aimed to evaluate CPT potentials in COVID-19 treatment, by performing systematic review and meta-analysis of studies in COVID-19 and other similar viral respiratory diseases, including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Influenza. Method: PubMed and Google scholars database were used to collect publications up to June 6, 2020. We included all studies reported clinical outcomes of severe to critically ill viral respiratory diseases patients. Review/systematic review/meta-analysis and articles not written in English, ineligible for full-access were excluded. Meta-analysis used Mantel-Haezel Risk Ratio (RR) with 95% confidence interval for dichotomous data, while mean difference was calculated for continuous data with random effect model. Pooled analysis for individual patients data were performed with Inverse Variance Weighted Average using random effect model. The study is registered with PROSPERO, number CRD42020190579. Result: Our search identified 3,786 studies. Nineteen studies with 436 participants were included in the meta-analysis. Pooled analysis showed reduction of mortality [RR 0.46 (0.24, 0.86), z=2.41(p=0.02), I 2 =68% (p=0.003)] and higher number of discharged patients [RR 1.28 (1.12, 1.46), z=3.61 (p=0.0003), I 2 =73% (p=0.002)] in CPT groups. The mean time to discharge in COVID-19 patients after receiving CPT is 18.35 days. Possible CPT mechanism of action is due to its ability to immediately reduce viral titer [Mean diff -0.68(-0.94, -0.41), z=5.03 (pInterpretation: CPT offers an easier and safer application during this pandemic, particularly when specific vaccines and medications are not yet available. Further investigation involving more patients and in combination with other treatment modalities are urgently needed. Funding: NoneDeclaration of Interests: All authors have nothing to declare.

Middle East Respiratory Syndrome in Al Ahsa, Saudi Arabia, 2015-18: A lingering epidemic

Middle East respiratory syndrome (MERS), an emerging disease with fatal outcomes, has limited information on regional variations and their impact on the control measures. The aim of this study was to describe data on distribution of and possible association of risk factors for the disease and poorer outcomes, and recommendations for better control of the disease. Data were collected for 2015-2018 in Al Ahsa, the largest region (population 1.2 million) in the eastern part of Saudi Arabia. &#x0D; In total, 103 cases were reported during the study period with fever and cough as predominant presenting symptoms. The majority were male, &gt;50 years old, and Saudi nationals. One third of patients had comorbid conditions (diabetes and cardiac predominantly). Occupation profiles of the patients varied, with camel owners and security personnel constituting 40% of the study population. &#x0D; In conclusions, older age, nationality, extracorporeal membrane oxygenation (ECMO) treatment, and associated comorbid conditions were found to be probable risk factors for poor outcomes. The mortality rate (59%) was distinctly higher in patients aged &gt;60 years. The study highlights probable risk factors for poor outcomes in MERS patients, and discusses scope for further intervention and better management.

Convalescent plasma to treat coronavirus disease 2019 (COVID-19): considerations for clinical trial design.

KEY IDEAS Case series studying convalescent plasma use in the treatment of COVID‐19 have been promising, but additional, high‐quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness.Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor.There are many clinical trials studying treatment of, and prophylaxis against, COVID‐19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the “Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID‐19” protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.

Pharmacologic Treatments and Supportive Care for Middle East Respiratory Syndrome.

Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.

Middle East Respiratory Syndrome: Its Occurrence, Aetiology, Epidemiology, Associated Clinicopathological Findings, Diagnosis, Prevention and Control in Humans and Animals: An Overview

Middle East respiratory syndrome (MERS) is a serious zoonotic disease. It is characterized by severe infection of the lower respiratory pathway in humans. Dromedary camels are considered to be the likeliest source of the very pathogenic aetiologic agent, Middle East respiratory syndrome coronavirus (MERS-CoV). Although, the first case of MERS-CoV was initially identified in Kingdom of Saudi Arabia (KSA) in September 2012, most of the reported cases have been detected in Arabian Peninsula but worthy of note is that travel-associated MERS cases have been reported around the world especially in Europe, Asia, Africa and North-America. This virus is very endemic in camel populations of East Africa and the Arabian Peninsula but worryingly, the zoonotic transmission of MERS-CoV are now well reported. It is diagnosed in camels using IgG immunofluorescence assay, protein microarray and virus neutralisation assay Diagnosis in humans is based on chest radiographs and computed tomographic scans but confirmatory diagnosis of suspected MERS patients could be done by taking a intratracheal aspirate for detection test of MERS-CoV RNA positive real-time reverse transcriptase polymerase chain reaction assays. The major control measures of MERS-CoV spread include strict regulation of camel movement, regular herd screening and culling of infected camels.

Airflow analysis of Pyeongtaek St Mary's Hospital during hospitalization of the first Middle East respiratory syndrome patient in Korea.

Middle East respiratory syndrome (MERS) is known to be transmitted through close contact. However, epidemiological surveys of MERS in Korea indicated that some secondary patients were infected without close contact. Therefore, the possibility of other transmission routes must be identified. In this study, the possibility of MERS spreading through airflow was investigated on the eighth floor of Pyeongtaek St Mary's Hospital. Computational fluid dynamics was used to analyse the indoor airflow and passive tracer diffusion during the index patient's stay. Six cases were simulated for different outdoor wind directions and indoor mechanical ventilation operations. When a passive tracer was released in ward 8104, where the index patient was hospitalized, the passive tracer spread through the indoor airflow, which was created by the outdoor airflow. Ward 8109, which had the largest number of infected cases and was far distant from ward 8104, showed passive tracer concentration in all cases. This result indicates that MERS may have spread through airflow. The study results do not imply that the infection pathway of MERS is airborne. However, the results show the possibility of MERS spreading through airflow in specific environments such as poor ventilation environments.

Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome Patients Quarantined in Hospital: A Retrospective Chart Analysis.

ObjectiveLittle is known about the psychiatric complications or risk factors for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS) patients quarantined in hospital.MethodsA retrospective chart review was performed of all the patients admitted to the acute MERS inpatient unit at the NMC during the 2015 outbreak.Results30 (75%) were confirmed to be MERS-CoV positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%) exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis and medication during their hospital stay. Suspected MERS patients did not exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or confirmed MERS patients (age 41.15±18.64, male 37.0%) completed psychological assessments. A multiple linear regression analysis revealed that the Korean National Health and Nutrition Examination Survey-Short form and the Impact of Event Scale-Revised scores were significantly positively correlated with Patient Health Questionnaire-9 scores.ConclusionOur findings indicate that the acute treatment of MERS-CoV infections in quarantine had a significant impact on the patients’ mental health. Furthermore, assessment of the risk factors for depression may identify vulnerable patients who require psychiatric care and attention during hospital quarantine.

Knowledge and Practice of Middle East Respiratory Syndrome Isolation Precaution among Hospital Nurses

Purpose The purposes of the study were to examine the knowledge and practice about Middle East Respiratory Syndrome (MERS) isolation precaution, and to explore influencing factors of the isolation practice among hospital nurses. Methods A total of 182 nurses were recruited from four general hospitals where MERS patients had been treated. The knowledge and practice of MERS isolation precaution were measured by the scales developed based on the CDC guidelines. The collected data were analyzed by SPSS/WIN 22 with descriptive statistics, T-test, One-way ANOVA, Pearson correlation coefficients, and hierachical multiple regression analysis. Results The nurses were 30 years old in average, and half of them had less than 5 years of clinical experience. and knowledge on droplet precautions (β=.171, p=.019) were the significant predictors, explaining 19.6% of variance in the MERS isolation guideline practice. Clinical experience (β=.225, p=.002), working at infection unit (β=-.203, p=.011). Conclusion The knowledge on droplet precaution and general knowledge on MERS were the important modifiable factor to improve the MERS isolation guideline practice among hospital nurses, even after adjusting clinical experience and demographic variables. It is necessary to develop an efficient education program on specific guidelines for prevention and management of infection by improving the knowledge on infectious disease such as MERS as well as droplet precaution which are modifiable factors. 주요어: 비말주의, 격리 지침, 지식, 수행도, MERS Key words: Practice guideline, Knowledge, Meddle East Respiratory Syndrome, Droplet precaution

Surveys and Proposals of the Infectious Disease Home Isolation through Middle East Respiratory Syndrome (MERS) Transmission

Background The purpose of this study was to identify the degree of home isolation and to determine what is needed for an effective home isolation through experience with home isolation that has been found to be in close contact persons with MERS-confirmed patient. Methods We conducted a questionnaire survey of employees at a university hospital in Seoul, Korea, which were classified as close contact with the MERS patient who visited the emergency room in June 2015. The questionnaire items were prepared by referring to the MERS response guideline, 3-3 edition. Results There were 81respondents in total. At the time of home isolation notification, 74 (91.4%) were guided by the instructions. At the time of home isolation notification, 42 (51.9%) persons were out of the home. When they comed back home, 7 (16.7%) persons were ambulanced-supported, but 14 (33.3%) used public transportation. the performance of “keeping inside home” was 4.51 out of 5, and the perfomance of “twice daily monitoring” was 3.68 out of 5. Conclusion As the result of survey suggests, overall isolation practices were satisfactory, but there were difficulties in home isolation practices such as the supply of daily necessities, monitoring of symptom manifestations, and worries about family infections. Therefore, it is advisable to fix the home isolation problems in tandem with the isolation of facilities.

Cross-sectional study of MERS-CoV-specific RNA and antibodies in animals that have had contact with MERS patients in Saudi Arabia.

BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged coronavirus that is associated with a severe respiratory disease in humans in the Middle East. The epidemiological profiles of the MERS-CoV infections suggest zoonotic transmission from an animal reservoir to humans.MethodsThis study was designed to investigate animal herds associated with Middle East respiratory syndrome (MERS)-infected patients in Saudi Arabia, during the last three years (2014–2016). Nasal swabs and serum samples from 584 dromedary camels, 39 sheep, 51 goats, and 2 cattle were collected. Nasal samples from camels, sheep, goats, and cattle were examined by real-time reverse-transcription PCR (RT-PCR) to detect MERS-CoV RNA, and the Anti-MERS ELISA assay was performed to detect camel humeral immune response (IgG) to MERS-CoV S1 antigen infection. The complete genome sequencing of ten MERS-CoV camel isolates and phylogenetic analysis was performed.ResultsThe data indicated that seventy-five dromedary camels were positive for MERS-CoV RNA; the virus was not detected in sheep, goats, and cattle. MERS-CoV RNA from infected camels was not detected beyond 2 weeks after the first positive result was detected in nasal swabs obtained from infected camels. Anti-MERS ELISA assays showed that 70.9% of camels related to human cases had antibodies to MERS-CoV. The full genome sequences of the ten MERS-CoV camel isolates were identical to their corresponding patients and were grouped together within the larger MERS-CoV sequences cluster for human and camel isolates reported form the Arabian Peninsula.ConclusionsThese findings indicate that camels are a significant reservoir for the maintenance of MERS-CoVs, and they are an important source of human infection with MERS.

Impact of Comorbidity on Fatality Rate of Patients with Middle East Respiratory Syndrome

To date, 1841 cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported worldwide, with 652 deaths. We used a publically available case line list to explore the effect of relevant factors, notably underlying comorbidities, on fatal outcome of Middle East respiratory syndrome (MERS) cases up to the end of October 2016. A Bayesian Weibull proportional hazards regression model was used to assess the effect of comorbidity, age, epidemic period and sex on the fatality rate of MERS cases and its variation across countries. The crude fatality rate of MERS cases was 32.1% (95% credibility interval (CI): 29.9%, 34.3%). Notably, the incremental change of daily death rate was most prominent during the first week since disease onset with an average increase of 13%, but then stabilized in the remaining two weeks when it only increased 3% on average. Neither sex, nor country of infection were found to have a significant impact on fatality rates after taking into account the age and comorbidity status of patients. After adjusting for age, epidemic period, MERS patients with comorbidity had around 4 times the risk for fatal infection than those without (adjusted hazard ratio of 3.74 (95% CI: 2.57, 5.67)).

The experience of endotracheal intubation in Middle East respiratory syndrome patients -A case report-

After Middle East respiratory syndrome (MERS) was first confirmed in Korea on May 20, 2015, a total of 186 confirmed cases and 37 deaths occurred until the announcement of its cessation on December 23, 2015. MERS often causes severe pneumonia; accordingly, many patients require endotracheal intubation for mechanical ventilation. At our hospital, we treated 30 confirmed and 29 suspected cases and performed 9 endotracheal intubations in 8 of these patients, using conventional direct laryngoscopy (DL) and GlideScope video-laryngoscopy (GL). We faced difficulty in conducting endotracheal intubation due to the personal protective equipment and the limited bed height required for managing MERS patients. In such cases, GL improved the ease and direct confirmation of success of endotracheal intubation as compared to DL. In addition, we found that portable end-tidal CO2-monitoring devices may facilitate more precise and reliable confirmation of successful intubation. Keywords: Airway management; Intubation; Middle East respiratory syndrome coronavirus; Personal protective equipment

Nurses' Experience of Middle East Respiratory Syndrome Patients Care

Nurses' Experience of Middle East Respiratory Syndrome Patients Care

Resource impact of managing suspected Middle East respiratory syndrome patients in a UK teaching hospital

Clinical challenges exist in the management of hospitalized patients returning to the UK with potential Middle East respiratory syndrome coronavirus (MERS-CoV) infection, particularly with its clinical overlap with influenza, as demonstrated in this case-series and cost-analysis review of returning Hajj pilgrims. These patients were hospitalized with acute febrile respiratory illness, initially managed as potential MERS-CoV infections, but were eventually diagnosed with influenza. Additional costs were small, yet enhanced infection prevention measures created significant burdens on isolation rooms and staff time. Planning for predictable events such as Hajj is important for resource management. Here, in-house MERS-CoV diagnostic testing would have facilitated earlier diagnosis and discharge.