Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia.

BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. MATERIALS AND METHODS: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. RESULTS: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. CONCLUSION: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers.

Surveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, March 2016-March 2019.

During March 2016-March 2019, a total of 200,936 suspected cases of Middle East respiratory syndrome coronavirus infection were identified in Saudi Arabia; infections were confirmed in 698 cases (0.3% [0.7/100,000 population per year]). Continued surveillance is necessary for early case detection and timely infection control response.

Diabetes Mellitus, Hypertension, and Death among 32 Patients with MERS-CoV Infection, Saudi Arabia.

Diabetes mellitus and hypertension are recognized risk factors for severe clinical outcomes, including death, associated with Middle East respiratory syndrome coronavirus infection. Among 32 virus-infected patients in Saudi Arabia, severity of illness and frequency of death corresponded closely with presence of multiple and more severe underlying conditions.

Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017-2018.

We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.

Middle East Respiratory Syndrome Coronavirus Infection Dynamics and Antibody Responses among Clinically Diverse Patients, Saudi Arabia.

Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.

Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015.

Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5'UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5'UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.

Mortality rate of ICU patients with the Middle East Respiratory Syndrome - Coronavirus infection at King Fahad Hospital, Jeddah, Saudi Arabia.

OBJECTIVE: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a novel coronavirus circulating in the Arabian Peninsula since September 2012. It leads to significant respiratory disease and among patients with co-morbidities is associated with high mortality. This research studied the mortality rate of MERS-CoV among intensive care unit (ICU) patients and the correlation of mortality with different co-morbidities. METHODS: This was a retrospective observational study conducted at the Intensive Care Unit of the King Fahad Hospital, Jeddah, Saudi Arabia. Data was obtained through patient chart review. RESULTS: The total sample consisted of 52 laboratory-confirmed MERS-CoV infection patients. 39 patients died, with a 75% case-fatality rate. Many patients had underlying co-morbidities, including diabetes mellitus (51.9%), hypertension (46.2%), and chronic renal disease (21.2%). CONCLUSIONS: MERS-CoV ICU mortality remains markedly high due to a combination of factors; the disease process of MERS-CoV leads to multiple organ failure, particularly respiratory and renal failure.

Outbreak of Middle East Respiratory Syndrome at Tertiary Care Hospital, Jeddah, Saudi Arabia, 2014.

During March-May 2014, a Middle East respiratory syndrome (MERS) outbreak occurred in Jeddah, Saudi Arabia, that included many persons who worked or received medical treatment at King Fahd General Hospital. We investigated 78 persons who had laboratory-confirmed MERS during March 2-May 10 and documented contact at this hospital. The 78 persons with MERS comprised 53 patients, 16 healthcare workers, and 9 visitors. Among the 53 patients, the most probable sites of acquisition were the emergency department (22 patients), inpatient areas (17), dialysis unit (11), and outpatient areas (3). Infection control deficiencies included limited separation of suspected MERS patients, patient crowding, and inconsistent use of infection control precautions; aggressive improvements in these deficiencies preceded a decline in cases. MERS coronavirus transmission probably was multifocal, occurring in multiple hospital settings. Continued vigilance and strict application of infection control precautions are necessary to prevent future MERS outbreaks.

Healthcare policies, precautionary measures and outcomes of mass gathering events in the era of COVID-19 pandemic: Expedited review.

With the onset of the COVID-19 pandemic in early 2020, several countries suspended or restricted mass gathering (MG) events to mitigate the risk of superspreading events. Prohibiting MGs aimed to lessen the likelihood of highly infectious persons coming into close contact with many others. Now that the world has opened its doors wide and removed most of precautionary measures, many questions arise. In this review, we aimed to summarize the current evidence regarding the policies and regulations that were implemented for the safe return of MG events. Besides, we highlighted the impact of the return of MG events during 2021 on the trajectory of COVID-19 spread. Canceling MG events can carry religious, societal, economic, and public negative consequences necessitating the safe return of these events. The experience with the COVID-19 pandemic was the foundation for the recommendations for the safe conduction of MG events during the pandemic by international public health bodies. When policymakers adequately applied precautionary measures and strategic approaches, we witnessed the safe holding of huge MG events without aggravating the COVID-19 situation or increasing the number of new cases beyond the capacity and readiness of the national healthcare system.

Epidemiology of tuberculosis in Saudi Arabia following the implementation of end tuberculosis strategy: Analysis of the surveillance data 2015-2019.

OBJECTIVES: To analyze the evolution of tuberculosis (TB) epidemiology in Saudi Arabia in the 5 years following the implementation of the end-TB Strategy. METHODS: A retrospective analysis of surveillance data, reported by the national tuberculosis control program from 2015-2019, was carried out. The annual incidence and the percentage of yearly changes were calculated and compared to the World Health Organization (WHO) milestones, which anticipate a 4-5% annual decline. Additionally, various other epidemiological indicators of TB were examined. RESULTS: The national TB incidence declined from 10.55% per 100,000 in 2015 to 8.76% per 100,000 in 2019, aligning with the WHO's 2019 milestone estimated between 8.59-8.96% per 100,000. While Makkah Region (40.3%) and Riyadh (24.6%) accounted for the majority of cases, Jazan region consistently exhibited the highest incidence throughout the study period. Demographic features shifted towards a younger age category, male, and native dominance. There was a consistent decrease in resistance and intermediate sensitivity to all first-line anti-TB drugs, associated with a substantial decrease in both polydrug resistance (from 4.7-1.9%; p<0.001) and multidrug resistance (from 4.4-2.4%; p=0.008). CONCLUSION: The figures of TB incidence TB in Saudi Arabia between 2015-2019 has met the WHO end-TB milestones, predicting successful progress toward the 2035 goal.

Does ChAdOx1-S and BNT162b2 heterologous prime-boost vaccination trigger higher rates of vaccine-related adverse events?

Background: There has been significant international interest in heterologous prime-boost COVID-19 vaccination. However, it is linked with different intensity and frequency of adverse events. This study aimed to assess the safety of ChAdOx1-S and BNT162b2 vaccines when given as heterologous prime-boost vaccination in Saudi Arabia. Methods: A cross-sectional study was conducted during the period October 2021 to March 2022. The study included two groups of people based on the type of vaccination regimen. The first group (heterologous) was subjected to different prime-boost vaccination schedules irrespective of the prime and boost vaccine types. The second group included people vaccinated with the same type of COVID-19 vaccine (homologous). Results: The overall sample included 334 participants. Those included in the heterologous group were at about 1.5 fold -increased risk for developing local and systemic adverse events compared to the homologous group. Fever, headache, and vomiting were significantly more frequent among the heterologous group compared to the homologous group (p-value<0.05). In both groups, more than half of the recorded adverse events were mild/moderate in severity. Conclusion: Heterologous prime-post vaccination is associated with a slightly increased risk for the development of local and systemic adverse events compared to the homologous regimen. However, most of these adverse events are mild/moderate in nature and recede within two days with no serious adverse events documented.

Clinical features and outcome of human Mpox (Monkeypox) in Saudi Arabia: An observational study of travel-related cases.

BACKGROUND: The 2022 Monkeypox virus (Mpox) outbreak had involved multiple countries around the globe. Here, we report clinical features and outcome of human Mpox of the first cases in Saudi Arabia. METHODS: We obtained records of confirmed Mpox cases in Saudi Arabia from the public electronic health information system, Health Electronic Surveillance Network (HESN) and the healthcare providers completed a de-identified structured clinical data collection form. RESULTS: The reported seven cases were travel-related and all were males between 24 and 41 years of age (mean age + SD) was 30.14 (+ 6.69) years. Of the cases, three (43 %) had heterosexual contact and the others had other intimate encounters while traveling abroad. They presented with skin lesions (100 %), fever (86 %), and lymphadenopathy (71 %). The illness was mild to moderate, did not require antiviral medications, and lasted 7-15 days. The mean duration of skin rash (+ SD) was 10 (+ 2.68) days. Routine laboratory tests (CBC, BUN, serum electrolytes, and liver enzymes) were within normal limits, and initial screening for HIV was negative. Expanded contact tracing did not reveal secondary cases of Mpox in the community or the healthcare setting. CONCLUSION: The current study showed heterosexual transmission of Mpox and the clinical course was mild and non-complicated. Therefore, clinicians and public health professionals should consider Mpox among individuals presenting with skin rash especially in the context of the investigation of HIV and other sexually transmitted diseases.

Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Adverse events following administration of COVID-19 vaccines in Saudi Arabia.

Previous studies investigated the frequency of different adverse events of COVID-19 vaccines. However, this study compares these adverse events between the two main COVID-19 vaccines used in Saudi Arabia (Pfizer-BioNTech and Oxford-AstraZeneca) using telemedicine technology. A cross-sectional study was conducted among 958 individuals, 7 days after receiving either Pfizer-BioNTech or Oxford-AstraZeneca vaccines during June 2021. Immediate adverse events were reported by 1.04% and 2.09% for Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively, with no serious events. Recipients of Pfizer-BioNTech vaccine had a higher percentage of local adverse events (24.8% versus 9.8% in AstraZeneca vaccine). The most common reported systemic adverse events in both vaccines respectively were general fatigue (23.1% and 25.1%), fever (18.5% and 27.2%), myalgia (20.6% and 20.3%), and headache (15.2% and 17.2%). No significant difference was recorded between both vaccines regarding overall systemic adverse events; however, they were more frequent following the first dose of AstraZeneca vaccine compared to Pfizer-BioNTech vaccine, while the reverse was observed for the second dose. Adverse events were more frequent in females and younger age groups for both vaccines. Most of systemic and local adverse events were mild in nature. Further cohort studies are recommended to investigate the long-term adverse events of COVID-19 vaccines.

A combined model for COVID-19 pandemic control: The application of Haddon's matrix and community risk reduction tools combined.

INTRODUCTION: To mitigate morbidity, mortality, and impacts of COVID-19 on health, it was essential to implement a comprehensive framework for COVID-19 control and prevention. A well-recognized tool from the field of injury prevention known as the Haddon matrix was utilized. The matrix states that any accident is affected by the host, agent, and environment. Another well-recognized tool used by the national fire protection association known as the Community risk reduction tool (CRR). The (CRR) tool utilizes the Five E's of Community Risk Reduction. AIM OF THE STUDY: To describe the risk factors that increase the susceptibility and the severity of COVID-19 infection based on the Haddon matrix and the proposed prevention strategies by the CRR tool by using the combined model. METHODOLOGY: We reviewed the literature to assess known factors contributing to COVID-19 susceptibility, infection, and severity of infection. We then used the Haddon matrix to structure, separating human factors from technical and environmental details and timing. We then used the community risk reduction (CRR) model to set all responses and control measures for each element obtained from the Haddon matrix tool. Subsequently, we incorporated both tools to develop the combined model. CONCLUSION: we proposed and implemented a combined model that utilizes the CRR model as the systematic strategy for the more theoretical framework of Haddon's matrix. Combining both models was practical and helpful in planning the preparedness and control of the COVID-19 pandemic in Saudi Arabia that can be generalized to national and international levels.

Hajj 2021: Role of mitigation measures for health security.

PURPOSE: After the impressive results of the 2020 Hajj management, Saudi authorities decided to expand the quota to 60,000 pilgrims in 2021, which resulted in a convenient and successful experience. PATIENTS AND METHODS: This was a retrospective pre and post-study study conducted on all pilgrims attending the 2021 Hajj using the polymerase chain reaction (PCR) test surveillance with paired-swab samples (pre-Hajj and post-Hajj) to evaluate the risk potential of COVID-19 among Hajj pilgrims, the effectiveness of preventive measures and the potential effect of the Hajj ritual as a huge mass gathering on the epidemiological situation of the Saudi Arabian population. RESULT: Forty-one cases had positive COVID-19 infections out of a total of 58,428 pilgrims who attended the 2021 Hajj season, as detected by nonmandatory pre- and post-Hajj PCR. Notably, the 2021 Hajj season achieved a decreasing leg of the COVID-19 pandemic curve. The adjusted incidence rate in KSA from July 11th to August 7th ranged from 19 to 24 cases per 100,000 population. In contrast, the incidence rate for the same duration in Hajj ranged from 3 to 7 cases per 100,000 pilgrims. CONCLUSION: The Saudi mitigation plan ensured the safety of pilgrims and healthcare workers for Hajj, successfully limited the risk of COVID-19 transmission inside and contributed to global health security. The success story of Hajj in 2020 and 2021 during the pandemic represents a successful model for planning, achieving and managing future mass gatherings by integrating technology with global and national health policies and public health measures.

Prevalence of asthma symptoms and associated risk factors among adults in Saudi Arabia: A national survey from Global Asthma Network Phase â .

PURPOSE: Estimating the prevalence and severity of asthma symptoms with standardized methods of population-based surveys is a critical step in reducing asthma burden. However, no sufficient surveys have been conducted in most countries of the Middle East especially at the national level. In this survey, we applied sound measures to estimate the prevalence and severity of asthma symptoms and related risk factors in adults in Saudi Arabia. PATIENTS AND METHODS: In this national cross-sectional study, the prevalence and severity of asthma symptoms were estimated throughout the country. Overall, 7955 adult individuals were selected from 20 regions across Saudi Arabia through their children at schools using a multistage, stratified cluster-sampling technique. A validated questionnaire, including the core and environmental questions of the Global Asthma Network questionnaires, was applied from March 4 to April 25, 2019. In addition, multivariate logistic regression analysis was performed to investigate the independent relationships between current wheeze and related risk factors. RESULTS: The overall prevalence of current wheeze (wheeze during the past 12 months) was 14.2%. Among persons with current wheeze, 38.1% were affected by severe asthma symptoms. Although a high percentage of those who had experienced asthma-ever reported that their asthma was diagnosed by doctors (83.3%), only 38.4% had a written plan for controlling their asthma. Women were more likely to develop current wheeze (adjusted odds ratio (aOR) 1.4; 95% CI: 1.1-1.7), while other statistically significant factors associated with current wheeze were jobs (aOR 11.8; 95% CI: 7.3-18.9), current exposure to moisture or damp spots (aOR 2.2; 95% CI: 1.5-3.4), heating the house when it is cold (aOR 1.7; 95% CI: 1.3-2.1), and ever using tobacco daily (aOR 2.7; 95% CI: 2.0-3.5). CONCLUSIONS: These findings provide enough evidence for health authorities in Saudi Arabia about the prevalence and severity of asthma symptoms, asthma control, and associated risk factors to scale up monitoring projects, control plans, and high-impact interventions.

The burden of asthma among children and adolescents in Saudi Arabia: A national cross-sectional survey.

Background: Asthma disease is one of the most common chronic diseases of childhood. Studies assessing asthma prevalence in Saudi Arabia have been variable and not recently updated. Objectives: We sought to assess asthma prevalence, severity, and related risk factors among children and adolescents in Saudi Arabia. Methods: A national, cross-sectional design was used following the Global Asthma Network phase I design. A total of 3817 children aged 6 to 7 years and 4138 adolescents aged 13 to 14 years were recruited from 137 primary and 140 intermediate schools across 20 regions by using a multistage stratified cluster sampling technique. Standardized written questionnaires were answered by the adolescents and by the parents or guardians of the children. The adolescents also answered a video-based questionnaire. Results: Overall, the prevalences of current wheeze were 10.4% and 13.3% and the prevalences of asthma ever were 13.8% and 15.7%, % in children and adolescents, respectively. Of all the children and adolescents, 5.2% and 5.6% had symptoms of severe asthma, respectively. Among those who reported asthma, 86.0% of the children and 74.8% of the adolescents had their asthma confirmed by a doctor, and 53.0% and 32.4%, respectively, were provided with a written plan to control their asthma. The main risk factors associated with current wheeze included antibiotic use in the first year of life, a history of being diagnosed with pneumonia in children, paracetamol use, and having a cat at home during the past 12 months in adolescents. Conclusions: The prevalence of asthma in children and adolescents in Saudi Arabia is within the average international range and is at a plateau phase.