Middle East respiratory syndrome coronavirus disease is rare in children: An update from Saudi Arabia

AIM To summarize the reported Middle East respiratory syndrome-coronavirus(MERS-Co V) cases, the associated clinical presentations and the outcomes. METHODS We searched the Saudi Ministry of Health website, the World Health Organization website, and the Flutracker website. We also searched MEDLINE and Pub Med for the keywords: Middle East respiratory syndromecoronavirus, MERS-Co V in combination with pediatric, children, childhood, infancy and pregnancy from the initial discovery of the virus in 2012 to 2016. The retrieved articles were also read to further find other articles. Relevant data were placed into an excel sheet and analyzed accordingly. Descriptive analytic statistics were used in the final analysis as deemed necessary.RESULTS From June 2012 to April 19, 2016, there were a total of 31 pediatric MERS-Co V cases. Of these cases 13(42%) were asymptomatic and the male to female ratio was 1.7:1. The mean age of patients was 9.8 ± 5.4 years. Twenty-five(80.6%) of the cases were reported from the Kingdom of Saudi Arabia. The most common source of infection was household contact(10 of 15 with reported source) and 5 patients acquired infection within a health care facility. Using real time reverse transcriptase polymerase chain reaction of pediatric patients revealed that 9 out of 552(1.6%) was positive in the Kingdom of Saudi Arabia. CONCLUSION Utilizing serology for MERS-CoV infection in Jordan andSaudi Arabia did not reveal any positive patients. Thus, the number of the pediatric MERS-CoV is low; the exact reason for the low prevalence of the disease in children is not known.

Regional variation of pediatric inflammatory bowel disease in Saudi Arabia: Results from a multicenter study

BACKGROUND Incidence and severity variations of inflammatory bowel disease(IBD)have been reported from Western populations between continents and regions of the same countries.However,no data were available from other countries.AIM To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia.METHODS Data from a national multicenter IBD study were used.The incidence,time trend,and clinical presentation of Crohn’s disease(CD)and ulcerative colitis(UC)in the Central region(CR),Western region(WR),and Eastern region(ER)were analyzed and compared.Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters.A P<0.05 was considered significant.RESULTS The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR.Consanguinity rate was higher in children with CD and UC from the CR and the ER,respectively.The incidences and time trends of CD and UC were not significantly different between regions.In the ER,a significantly higher percentage of children with CD presented with abdominal pain(P<0.001),blood in stools(P=0.048),stricturing or penetrating disease(P=0.029),higher erythrocyte sedimentation rate(P<0.001),higher C-reactive protein(P<0.001),higher anemia(P=0.017),and lower albumin level(P=0.014).For children with UC from the ER,a significantly higher percentage presented with anemia(P=0.006)and a lower percentage with pancolitis(P<0.001).CONCLUSION The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia.Prospective studies are needed to explain such variations.

New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis

BACKGROUND Diabetes mellitus(DM)is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019(COVID-19).The relationship between diabetes and COVID-19 is known to be bidirectional.AIM To analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes,pre-existing diabetes,hyperglycemic,and non-diabetes among COVID-19 patients.METHODS We used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis.Online databases were searched for all peerreviewed articles published until November 6,2020.Articles were screened using Covidence and data extracted.Further analysis was done using comprehensive meta-analysis.Among the 128 studies detected after thorough database searching,seven were included in the quantitative analysis.The proportion was reported with 95%confidence interval(CI)and heterogeneity was assessed using I2.RESULTS Analysis showed that 19.70%(CI:10.93-32.91)of COVID-19 patients had associated DM,and 25.23%(CI:19.07-32.58)had associated hyperglycemia.The overall mortality rate was 15.36%(CI:12.57-18.68)of all COVID-19 cases,irrespective of their DM status.The mortality rate was 9.26%among non-diabetic patients,10.59%among patients with COVID-19 associated hyperglycemia,16.03%among known DM patients,and 24.96%among COVID-19 associated DM patients.The overall occurrence of adverse events was 20.52%(CI:14.21-28.70)among COVID-19 patients in the included studies,15.29%among non-diabetic patients,20.41%among patients with COVID-19 associated hyperglycemia,20.69%among known DM patients,and 45.85%among new-onset DM.Metaregression showed an increasing rate of mortality among new hyperglycemic patients,known diabetics,and new-onset DM patients in comparison to those without diabetes.CONCLUSION A significantly higher rate of new onset DM and hyperglycemia was observed.Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.

Infectious causes of fever of unknown origin in developing countries: An international ID-IRI study

Background:Fever of unknown origin(FUO)in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of FUO.Methods:A multi-center study for infectious causes of FUO in lower middle-income countries(LMIC)and lowincome countries(LIC)was conducted between January 1,2018 and January 1,2023.In total,15 participating centers from seven different countries provided the data,which were collected through the Infectious DiseasesInternational Research Initiative platform.Only adult patients with confirmed infection as the cause of FUO were included in the study.The severity parameters were quick Sequential Organ Failure Assessment(qSOFA)≥2,intensive care unit(ICU)admission,vasopressor use,and invasive mechanical ventilation(IMV).Results:A total of 160 patients with infectious FUO were included in the study.Overall,148(92.5%)patients had community-acquired infections and 12(7.5%)had hospital-acquired infections.The most common infectious syndromes were tuberculosis(TB)(n=27,16.9%),infective endocarditis(n=25,15.6%),malaria(n=21,13.1%),brucellosis(n=15,9.4%),and typhoid fever(n=9,5.6%).Plasmodium falciparum,Mycobacterium tuberculosis,Brucellae,Staphylococcus aureus,Salmonella typhi,and Rickettsiae were the leading infectious agents in this study.A total of 56(35.0%)cases had invasive procedures for diagnosis.The mean qSOFA score was 0.76±0.94{median(interquartile range[IQR]):0(0–1)}.ICU admission(n=26,16.2%),vasopressor use(n=14,8.8%),and IMV(n=10,6.3%)were not rare.Overall,38(23.8%)patients had at least one of the severity parameters.The mortality rate was 15(9.4%),and the mortality was attributable to the infection causing FUO in 12(7.5%)patients.Conclusions:In LMIC and LIC,tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

Structure-based discovery of F.religiosa phytochemicals as potential inhibitors against Monkeypox(mpox)viral protein

Outbreaks of Monkeypox(mpox)in over 100 non-endemic countries in 2022 represented a serious global health concern.Once a neglected disease,mpox has become a global public health issue.A42R profilinlike protein from mpox(PDB ID:4QWO)represents a potential new lead for drug development and may interact with various synthetic and natural compounds.In this report,the interaction of A42R profilinlike protein with six phytochemicals found in the medicinal plant Ficus religiosa(abundant in India)was examined.Based on the predicted and compared protein–ligand binding energies,biological properties,IC_(50) values and toxicity,two compounds,kaempferol(C-1)and piperine(C-4),were selected.ADMET characteristics and quantitative structure–activity relationship(QSAR)of these two compounds were determined,and molecular dynamics(MD)simulations were performed.In silico examination of the kaempferol(C-1)and piperine(C-4)interactions with A42R profilin-like protein gave best-pose ligandbinding energies of–6.98 and–5.57 kcal/mol,respectively.The predicted IC_(50) of C-1 was 7.63 lM and 82 lM for C-4.Toxicity data indicated that kaempferol and piperine are non-mutagenic,and the QSAR data revealed that piperlongumine(5.92)and piperine(5.25)had higher log P values than the other compounds examined.MD simulations of A42R profilin-like protein in complex with C-1 and C-4 were performed to examine the stability of the ligand–protein interactions.As/C and C-4 showed the highest affinity and activities,they may be suitable lead candidates for developing mpox therapeutic drugs.This study should facilitate discovering and synthesizing innovative therapeutics to address other infectious diseases.

Prevalence of Depression in Elderly People Living With HIV:A Systematic Review and Meta-analysis

We conducted a systematic review andmeta-analysis to determine the prevalence of depression among elderly people living with HIV.We searched electronic databases and included 12 observational studies that reported on depression among people who were 50 years of age or older and had HIV.The studies were mostly hospital-based and fromWestern and African countries.They included a total of 5868 older peoplewith HIV,ofwhom 1667 had depression.Pooled prevalence of depression was 28%with heterogeneity of 95.2%.Prevalence ranged from 14.5%in the Netherlands to 42.4%in South Africa.Although therewas asymmetry in the funnel plot,the Egger’s test showed no significant publication bias.Our meta-analysis found a high burden of depression among older people with HIV.Comprehensive health services addressing psychosocial needs and interventions to prevent and treat depression are needed,especially in community settings.Healthcare providers and policymakers should address the prevalence of depression in such communities.

Cholera:an overview with reference to the Yemen epidemic

Cholera is a secretory diarrhoeal disease caused by infection with Vibrio cholerae, primarily the V. cholerae O1 El Tor biotype. There are approximately 2.9 million cases in 69 endemic countries annually, resulting in 95 000 deaths. Cholera is associated with poor infrastructure and lack of access to sanitation and clean drinking water. The current cholera epidemic in Yemen, linked to spread of V. cholerae O1 (Ogawa serotype), is associated with the ongoing war. This has devastated infrastructure and health services. The World Health Organization had estimated that 172 286 suspected cases arose between 27th April and 19th June 2017, including 1170 deaths. While there are three oral cholera vaccines prequalified by the World Health Organization, there are issues surrounding vaccination campaigns in conflict situations, exacerbated by external factors such as a global vaccine shortage. Major movements of people complicates surveillance and administration of double doses of vaccines. Cholera therapy mainly depends on rehydration, with use of antibiotics in more severe infections. Concerns have arisen about the rise of antibiotic resistance in cholera, due to mobile genetic elements. In this review, we give an overview of cholera epidemiology, virulence, antibiotic resistance, therapy and vaccines, in the light of the ongoing epidemic in Yemen.

Molecular aspects of MERS-CoV

Middle East respiratory syndrome coronavirus （MERS-CoV） is a betacoronavirus which can cause acute respiratory distress in humans and is associated with a relatively high mortality rate. Since it was first identified in a patient who died in a Jeddah hospital in 2012, the World Health Organization has been notified of 1735 laboratory-confirmed cases from 27 countries, including 628 deaths. Most cases have occurred in Saudi Arabia. MERS-CoV ancestors may be found in Old World bats of the Vespertilionidae family. After a proposed bat to camel switching event, transmission of MERS-CoV to humans is likely to have been the result of multiple zoonotic transfers from dromedary camels. Human-to-human transmission appears to require close contact with infected persons, with outbreaks mainly occurring in hospital environments. Outbreaks have been associated with inadequate infection prevention and control implementation, resulting in recommendations on basic and more advanced infection prevention and control measures by the World Health Organization, and issuing of government guidelines based on these recommendations in affected countries including Saudi Arabia. Evolutionary changes in the virus, particularly in the viral spike protein which mediates virus-host cell contact may potentially increase transmission of this virus. Efforts are on-going to identify specific evidence-based therapies or vaccines. The broad-spectrum antiviral nitazoxanide has been shown to have in vitro activity against MERS-CoV. Synthetic peptides and candidate vaccines based on regions of the spike protein have shown promise in rodent and non-human primate models. GLS-5300, a prophylactic DNA-plasmid vaccine encoding S protein, is the first MERS-CoV vaccine to be tested in humans, while monoclonal antibody, m336 has given promising results in animal models and has potential for use in outbreak situations.

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.

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.