Sero-prevalence of Middle East Respiratory Syndrome Coronavirus among Camels at a Slaughterhouse in Kenya, 2015

Dromedary camels are implicated as reservoirs of MERS-CoV （Middle East Respiratory Syndrome coronavirus）. High prevalence of MERS-CoV antibodies in dromedaries in Africa and Arabian Peninsula was demonstrated from sera archived between 1992 and 2012 with matching of camel-derived and human-derived sequences from various regions suggesting zoonotic transmission. We assessed sero-prevalence of anti-MERS-CoV antibodies among dromedaries at Athi-River slaughterhouse, Kenya. Proportions were calculated and associations between anti-MERS-CoV antibody sero-positivity and age group, sex, and origin of camels were assessed using Chi-square tests. Out of 373 specimens, 53% were females, antibody sero-prevalence was 82%. Sero-prevalence did not differ by age group, sex, or origin. This study reports high sero-prevalence of MERS-CoV antibodies demonstrated among camels brought for slaughter from different regions of Kenya. This was consistent with other studies in Africa among adult camels and further proves that the virus likely remains present in Kenya. Since only mature camels were assessed, more studies on younger populations of camels could help determine the dynamics of virus transmission. Though the risk from mature animals is not known, at some point these camels become re-infected and human populations exposed to camels may still face some risks.

Serological Study of An Imported Case of Middle East Respiratory Syndrome and His Close Contacts in China, 2015

The first imported Middle East respiratory syndrome （MERS） case in China was identified in May 2015. We determined the kinetics of antibody （IgG and IgM） and neutralizing antibodies against MERS-coronavirus （MERS-CoV） in this case before discharge. Moreover, no seroconversion was found among 53 close contacts by anti-MERS IgG antibody enzyme-linked immunosorbent assay （ELISA） of paired serum samples. These findings suggest that neither community nor nosocomial transmission of MERS-CoV occurred in China.

Mental health impact of the Middle East respiratory syndrome,SARS,and COVID-19:A comparative systematic review and metaanalysis

BACKGROUND Over the last few decades,3 pathogenic pandemics have impacted the global population;severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV)and SARS-CoV-2.The global disease burden has attributed to millions of deaths and morbidities,with the majority being attributed to SARS-CoV-2.As such,the evaluation of the mental health(MH)impact across healthcare professionals(HCPs),patients and the general public would be an important facet to evaluate to better understand short,medium and long-term exposures.AIM To identify and report:(1)MH conditions commonly observed across all 3 pandemics;(2)Impact of MH outcomes across HCPs,patients and the general public associated with all 3 pandemics;and(3)The prevalence of the MH impact and clinical epidemiological significance.METHODS A systematic methodology was developed and published on PROSPERO(CRD42021228697).The databases PubMed,EMBASE,ScienceDirect and the Cochrane Central Register of Controlled Trials were used as part of the data extraction process,and publications from January 1,1990 to August 1,2021 were searched.MeSH terms and keywords used included Mood disorders,PTSD,Anxiety,Depression,Psychological stress,Psychosis,Bipolar,Mental Health,Unipolar,Self-harm,BAME,Psychiatry disorders and Psychological distress.The terms were expanded with a‘snowballing’method.Cox-regression and the Monte-Carlo simulation method was used in addition to I2 and Egger’s tests to determine heterogeneity and publication bias.RESULTS In comparison to MERS and SARS-CoV,it is evident SAR-CoV-2 has an ongoing MH impact,with emphasis on depression,anxiety and post-traumatic stress disorder.CONCLUSION It was evident MH studies during MERS and SARS-CoV was limited in comparison to SARS-CoV-2,with much emphasis on reporting symptoms of depression,anxiety,stress and sleep disturbances.The lack of comprehensive studies conducted during previous pandemics have introduced limitations to the“know-how”for clinicians and researchers to better support patients and deliver care with limited healthcare resources.

Life after recovery from SARS,influenza,and Middle East respiratory syndrome: An insight into possible long-term consequences of COVID-19

Viral infectious diseases have become an increased public health issue in the past 20 years.The outbreaks of severe acute respiratory syndrome coronavirus(SARSCoV-1)in 2002,influenza H1N1 in 2009,Middle East respiratory syndrome-CoV in 2012,and the current new coronavirus SARS-CoV-2 have shown that viral infectious diseases are a major concern in the 21st century.As the world lives under the pandemic of a new coronavirus(COVID-19),knowing the clinical characteristics from those past diseases and their long-term outcomes is important to understand the current coronavirus pandemic and its complications and consequences better and plan for possible future outbreaks.Several long-term complications have been described with these respiratory viral diseases,such as decreased pulmonary function,pulmonary fibrosis,chronic fatigue syndrome,avascular necrosis of bone,polyneuropathy,encephalitis,posttraumatic stress disorder,depression,and anxiety.This article summarizes several studies describing chronic complications and long-term outcomes of patients recovered from these viral syndromes.

Genetic Evidence of Middle East Respiratory Syndrome Coronavirus(MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

We describe the first genome isolation of Middle East respiratory syndrome coronavirus(MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels(82.37%, 95%confidence interval(CI) 79.50–84.91). More female camels were significantly seropositive(74.28%, 95% CI 71.14–77.19)than male camels(P \ 0.001)(53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERSCoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4 b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.

Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin

The papain-like protease(PL^(pro)) of Middle-East respiratory syndrome coronavirus(MERS-CoV) has proteolytic,deubiquitinating,and de ISGylating activities.The latter two are involved in the suppression of the antiviral innate immune response of the host cell.To contribute to an understanding of this process,we present here the X-ray crystal structure of a complex between MERS-CoV PL^(pro) and human ubiquitin(Ub) that is devoid of any covalent linkage between the two proteins.Five regions of the PL^(pro) bind to two areas of the Ub.The C-terminal five residues of Ub,RLRGG,are similar to the P5–P1 residues of the polyprotein substrates of the PL^(pro) and are responsible for the major part of the interaction between the two macromolecules.Through sitedirected mutagenesis,we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL^(pro).The enzyme appears not to be optimized for catalytic efficiency; thus,replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities.Ubiquitin binding by MERS-CoV PL^(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL^(pro).The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL^(pro).

Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%—60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1-7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of < 150 ×10^9/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32 38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020

Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases<65 years but with a lower risk(adjusted OR=0.31,95%Cl:0.18-0.51)among male cases>65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

Middle East respiratory syndrome coronavirus： current situation and travel-associated concerns

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.

Diabetes Risk Factor and Its Relationship to Increasing Coronavirus (COVID-19) Mortality Rate in United States in 2019-2022: An Epidemiological Study

As an effort to understand the effect of diabetes on the increasing rate of COVID-19 infection, we embarked upon a detailed statistical analysis of various datasets that include COVID-19 infection and mortality rate, diabetes and diseases that may contribute to the severity and risk factor of diabetes in individuals and this impact on COVID-19 and the mortality rate. These diseases include respiratory diseases, cardiovascular diseases, and obesity. Equally significant is the statistical analysis on ethnicity, age, and sex on COVID-19 infection as well as mortality rate. Their possible contributions to increasing the severity and risk factor of diabetes as a risk to mortality to individuals who have COVID-19. Objectives: The ultimate objectives of this investigation are as follow: 1) Is there a risk factor of diabetes on COVID-19 infection and increasing mortality rate? 2) To what extent do other disease conditions that include, obesity, heart failure, and respiratory diseases influence the severity and risk factor of diabetes on increasing COVID-19 infection and mortality rate? 3) To what extent does age, race, and gender increase the mortality of COVID-19 and increase the severity and risk factor of diabetes on COVID-19 mortality rate? 4) How and why COVID-19 virus increases the risk of diabetes in children? 5) Diabetes and COVID-19: Who is most at Risk? Lastly, understanding the misconception of COVID-19 and diabetes.

Coronavirus: A “Mild” Virus Turned Deadly Infection

Coronaviruses are a family of viruses that can be transmitted from one person to another.Earlier strains have only been mild viruses,but the current form,known as coronavirus disease 2019(COVID-19),has become a deadly infection.The outbreak originated in Wuhan,China,and has since spread worldwide.The symptoms of COVID-19 include a dry cough,sore throat,fever,and nasal congestion.Antimicrobial drugs,pathogen–host interaction,and 2 weeks of isolation have been recommended for the treatment of the infection.Safe operating procedures,such as the use of face masks,hand sanitizer,handwashing with soap,and social distancing,are also suggested.Moreover,travel bans for cities,states,and countries have been put in place,along with lockdowns to control the outbreak.Travel restrictions,mask use,sanitizer or soap use,and avoidance of touching the face and nose have produced encouraging results,whereas the effectiveness of antibiotics has not been proved.The results of isolation for the recovery of infected people have also been promising.Travel bans and lockdowns have caused a slump in economies,and unemployment has risen sharply,resulting in an increase in mental health cases globally.To date,vaccines have been developed and are in use in certain countries,but following standard operating procedures remain critical.The countries following the guidelines can eradicate this virus.New Zealand was the rst country to eliminate the virus from their territory.

The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models

In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.

COVID-19 compared to other epidemic coronavirus diseases and theflu

Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory syndrome coronavirus(SARS-CoV) which caused the infamous 2002 outbreak, the Middle East respiratory syndrome coronavirus(MERS-CoV) which caused an outbreak in 2012, and now the SARS-CoV-2 [responsible for the current coronavirus disease 2019(COVID-19)] have all posed notable threats to global public health.But, how does the current COVID-19 outbreak compare with previous coronaviruses diseases? In this review, we look at the key differences between SARS-CoV, MERS-CoV, and SARS-CoV-2, and examine challenges in determining accurate estimates of the severity of COVID-19. We discuss coronavirus outbreaks in light of key outbreak severity indicators including,disease fatality, pathogen novelty, ease of transmission, geographical range, and outbreak preparedness. Finally, we review clinical trials of emerging treatment modalities and provide recommendations on the control of COVID-19 based on the mode of transmission of the coronaviruses. We also recommend the development and use of a standardized predictive epidemic severity models to inform future epidemic response.

Lucky China： Efficient Prevention from Middle East Respiratory Syndrome and its Beyond

Middle East respiratory syndrome （MERS） has recently drawn worldwide attention since its nosocomial or suspected community-acquired clusters in South Korea, which has been the largest and the most complex outbreak of the Middle East Region since 2012. It is such a large fortune for China to be able to prevent effectively from MERS, not only by actively monitoring the Korean imported case based on the notification of WHO Western Pacific Region Office （WPRO）, but also by properly quarantining a number of close contacts. Otherwise, China might undergo the same situation as in South Korea, or even worse, if the patient kept on traveling through Southern China or went to health care facilities without wearing any personal preventing equipment. To date, this laboratory-confirmed MERS patient has recovered and been discharged from hospital, and none of the close contacts （n = 75） has showed any associated symptoms, so lucky for him and China.

Controversies’ clarification regarding ribavirin efficacy in measles and coronaviruses: Comprehensive therapeutic approach strictly tailored to COVID-19 disease stages

BACKGROUND Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action,which supports its longevity and quality as a clinical resource.It has been widely administered for measles and coronavirus infections.Despite the large amount of data concerning the use of ribavirin alone or in combination for measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019(COVID-19)outbreaks,the conclusions of these studies have been contradictory.Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data,and these potential confounds should be addressed.AIM To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19.METHODS PubMed database was searched over a period of five decades utilizing the terms“ribavirin”alone or combined with other compounds in measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and COVID-19 infections.The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverseeffects.In vitro and animal studies were also retrieved.A chapter on ribavirin’s pharmacology was included as well.RESULTS In addition to the difficulties and pressures of an emerging pandemic,there is the burden of designing and conducting well-organized,double-blind,randomized controlled trials.Many studies have succumbed to specific pitfalls,one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies.Other pitfalls include study design inconsistent with the well-established clinical course of disease;inappropriate pharmacology of applied treatments;and the misinterpretation of study results with misconceived generalizations.A comprehensive treatment for COVID-19 is proposed,documented by thorough,longterm investigation of ribavirin regimens in coronavirus infections.CONCLUSION A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.

Coronavirus disease 2019 (COVID-19), MERS and SARS: Similarity and difference

SARS-CoV-2 is the causative agent of COVID-19.Since its outbreak in December 2019,COVID-19 has swept the globe.By 17 July 2020,the World Health Organization(WHO)had confirmed 13?119?239 cases and 573?752 deaths,and the numbers are still rising.Current evidence shows that COVID-19 is lower than severe acute respiratory syndrome and Middle East respiratory syndrome in terms of severity and mortality risk,although the infections are particularly more severe in patients with underlying medical conditions.The bulk of COVID-19 patients had close contact with confirmed cases,but an exact origin and specific transmission for COVID-19 are still unknown.As there is no approved antiviral treatment for COVID-19 infection,proper prevention and control practices are essential to control the infection.To have an insight view of COVID-19,we summarized and compared the etiology,clinical manifestations,diagnosis,treatment,and prevention measures of COVID-19,severe acute respiratory syndrome,and Middle East respiratory syndrome.

Middle East respiratory syndrome:what to be concerned more in preparedness?

The recent problem on Middle East respiratory syndrome is a very interesting new infection emerging from the Gulf area. For practitioners in intensive care medicine, knowledge update on this new emerging infection is needed. Preparation for diagnostic tool and antiviral drug to cope with possible outbreak is suggested. In addition, the consideration of ecological factors of this new disease is important. The consideration of not only ecological but also humanistic background can be useful to manage the new disease, Middle East respiratory syndrome as well. Finally, how to improve medical service for underserved population is a big issue. The local health department must play an important role.

Stochastic and spatio-temporal analysis of the Middle East Respiratory Syndrome outbreak in South Korea, 2015

South Korea was free of the Middle East Respiratory Syndrome(MERS)until 2015.The MERS outbreak in South Korea during 2015 was the largest outbreak of the Coronavirus outside the Middle East.The major characteristic of this outbreak is inter-or intra-hospital transmission.This recent MERS outbreak in South Korea is examined and assessed in this paper.The main objectives of the study is to characterize the pattern of the MERS outbreak in South Korea based on a basic reproductive ratio,the probability of ultimate extinction of the disease,and the spatio-temporal proximity of occurrence between patients.The survival function method and stochastic branching process model are adapted to calculate the basic reproductive ratio and the probability of ultimate extinction of the disease.We further investigate the occurrence pattern of the outbreak using a spatio-temporal autocorrelation function.

二肽基肽酶4为人类中东呼吸道综合征冠状病毒(MERS-CoV)功能性细胞受体

中东呼吸道综合征冠状病毒(Middle East respiratory syndrome coronavirus,MERS-CoV)是继SARS冠状病毒(SARS-CoV)之后新近出现的又一种能够引发严重呼吸道感染的人类新发冠状病毒.MERS-CoV于2012年9月首次在中东一些国家被发现,截至2013年9月7日,MERS-CoV已经引起114例感染病例,其中54人死亡,死亡率约50%.病毒受体研究为MERS-CoV等人类新发冠状病毒进化和跨种传播机制提供重要依据.最近,Raj等在Nature发表文章,首次报道了二肽基肽酶4(dipeptidyl peptidase 4,DPP4;又名CD26)为MERS-CoV感染细胞的功能性受体.MERS-CoV功能性受体的发现为人类新冠状病毒溯源和跨种进化研究、病毒传染和流行病学特征分析以及抗病毒药物和疫苗研究提供重要基础.

韩国中东呼吸综合征(MERS)大爆发:MERS-CoV可持续人际间传播能力是否增强?

2015年5月20日,韩国确诊了首例输入性中东呼吸综合征(MERS)病例,随后韩国出现了MERS病例的大爆发,成为继中东地区以外疫情最为严重的地区。截止到2015年7月26日,韩国已报告186例实验室确诊病例(包括在中国确诊1例),其中36人死亡。与其他地区输入病例传播情况不同,韩国MERS爆发,出现了三代病例,这是否说明中东呼吸综合征冠状病毒(MERS-Co V)可持续人际间传播能力增强?本文分析认为,MERS在韩国的爆发,主要源于韩国特殊的就诊环境和隔离重视程度不足,并非MERS-Co V可持续人际间传播能力增强。MERSCo V目前仍具有有限的可持续人际间传播能力。