A Narrative Review of the Coronavirus Disease 2019 Response in the Kingdom of Bahrain.

Background: The Kingdom of Bahrain has reported more than 696,000 cases of coronavirus disease 2019 (COVID-19) and 1548 associated deaths as of December 26, 2022. Objectives: To better inform responses to future public health threats, this narrative review documents the challenges and responses to the COVID-19 pandemic in the Kingdom of Bahrain. Methods: A PubMed search was conducted focusing on severe acute respiratory syndrome or COVID-19 in Bahrain. Additional relevant references were also included from the authors' personal reference collections. Results: The search indicated that Bahrain achieved well-established control of the pandemic through robust public health measures, including an early, comprehensive vaccination program. Bahrain was among the first countries to grant emergency authorization for COVID-19 vaccines; as of December 2022, nearly 73% of the eligible population has been fully vaccinated, and approximately 60% has been boosted. Low case rates in recent months highlight Bahrain's successful response to the COVID-19 pandemic. Conclusions: Early organization, robust and systematic protective measures, and a comprehensive vaccination program were key components of the Kingdom's response to the pandemic; traveler quarantines and attempts to combat misinformation were of little or no benefit. These lessons provide guidance for future preparedness to minimize the public health impacts of another pandemic. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX).

Safety and efficacy of COVID-19 prime-boost vaccinations: Homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals.

BACKGROUND: Booster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied. METHODS: We conducted a non-randomized, non-blinded phase II observational community trial acrossBahrain, investigating the reactogenic and immunogenic responseof participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological statuswas determined at baseline and on the following 8thweek. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling. RESULTS: 305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study,with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred. CONCLUSION: Heterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated. Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.

Spontaneous Resolution of Drug-Resistant Epilepsy in Patients with Sturge-Weber Syndrome.

Introduction: Sturge-Weber syndrome (SWS) is often associated with drug resistant epilepsy. The literature is unclear as to how often these patients can be weaned off of antiepileptic drugs (AEDs) to become seizure-free. Case Description: We describe two patients with SWS. After initial treatment with various AEDs, breakthrough seizures still occurred. However, after periods with no seizure activity, they were weaned off of their medications. They have been off for 4 and 3 years and seizure-free for 13 and 12 years, respectively. No surgical procedure was necessary. Conclusion: We hypothesize that spontaneous involution or pathological disconnection of the vascular malformations might underly the patients' recovery. The initial aggressive therapy, close follow-up, choice of AEDs, or natural evolution of the disease may have played a role in their recovery. Therefore, in patients with SWS and lesional structural epilepsy, medication freedom is possible and invasive management options including surgery should be discussed carefully.

Surgically Remediable Secondary Network Epileptic Encephalopathies With Continuous Spike Wave in Sleep: Lesions May Not Be Visible on Brain Magnetic Resonance Imaging (MRI).

BACKGROUND: Continuous spike wave in sleep (CSWS) is an electroencephalogram (EEG) pattern associated with developmental and epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS). This etiologically heterogeneous syndrome may occur because of genetic factors and congenital or acquired brain lesions. We studied the pattern of clinical presentation and underlying etiologies in patients with DEE-SWAS that respond to resective surgery. METHODS: We reviewed our clinical and research databases for patients who had resolution of CSWS following surgical resection of a focal lesion. RESULTS: We identified 5 patients meeting inclusion criteria. In 3 of 5, an epileptogenic structural abnormality was not apparent on brain magnetic resonance imaging (MRI). In all 3 patients, focal cortical dysplasia was identified through intracranial EEG monitoring. SIGNIFICANCE: DEE-SWAS may be a secondary bilateral network epilepsy syndrome, which can be treated with resection of the inciting focal lesion. In patients with drug-resistant CSWS, clinicians should consider a complete epilepsy presurgical workup, including intracranial EEG monitoring.

Diagnostic utility of specific abnormal EEG patterns in children for determining epilepsy phenotype and presence of structural brain abnormalities.

Objective: Estimate sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EEG findings: centrotemporal spikes, photoparoxysmal response, asymmetric photic driving, and asymmetric sleep spindles, for epilepsy phenotype and presence of structural brain abnormalities. Methods: In this case-control study we reviewed children referred for EEG over a 4-year period, with at least one of centrotemporal spikes, photoparoxysmal response, asymmetric photic driving, or asymmetric sleep spindles. This cohort was analyzed in combination with a research database of pediatric patients with seizures. Results: Centrotemporal spikes had 100% sensitivity for childhood epilepsy with centrotemporal spikes or atypical childhood epilepsy with centrotemporal spikes, but lower specificity (70%) and PPV (58%). Photoparoxysmal response had high specificity (92%) and NPV (92%) for genetic generalized epilepsy. Asymmetric photic driving had low sensitivity for structural brain abnormalities (17%), with specificity 80%. In contrast, asymmetric sleep spindles had much higher sensitivity and specificity, 44% and 97%, respectively. Conclusions: Although centrotemporal spikes are classically associated with childhood epilepsy with centrotemporal spikes, these discharges are seen in other conditions. Photoparoxysmal response is highly indicative of a genetic generalized epilepsy, though may be seen in other epilepsy phenotypes. Relative attenuation of sleep spindles is a more reliable indicator of structural brain malformation than asymmetric photic driving. Significance: The quantitative diagnostic utility of EEG findings should be considered when incorporating these results into clinical decision-making.

Safety and Immunogenicity of COVID-19 BBIBP-CorV Vaccine in Children 3-12 Years Old.

BACKGROUND AND OBJECTIVES: In the current COVID-19 pandemic, children below the age of 12 could manifest COVID-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. SUBJECTS AND METHODS: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. RESULTS: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to COVID-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to COVID-19. Children with previous COVID-19 exposure had higher averages of anti-S (2379 U/mL compared to 409.1), anti-N (177.6 U/mL compared to 30.9) and neutralizing antibody (93.7 U/mL compared to 77.1) than children with no prior exposure at day 35. CONCLUSIONS: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

COVID-19 Recovery Patterns Across Alpha (B.1.1.7) and Delta (B.1.617.2) Variants of SARS-CoV-2.

Background: B.1.1.7 (alpha) and B.1.617.2 (delta) variants of concern for SARS-CoV-2 have been reported to have differential infectivity and pathogenicity. Difference in recovery patterns across these variants and the interaction with vaccination status has not been reported in population-based studies. Objective: The objective of this research was to study the length of stay and temporal trends in RT-PCR cycle times (Ct) across alpha and delta variants of SARS-CoV-2 between vaccinated and unvaccinated individuals. Methods: Participants consisted of patients admitted to national COVID-19 treatment facilities if they had a positive RT-PCR test for SARS-CoV-2, and analysis of variants was performed (using whole genome sequencing). Information on vaccination status, age, sex, cycle times (Ct) for four consecutive RT-PCR tests conducted during hospital stay, and total length of hospital stay for each participant were ascertained from electronic medical records. Results: Patients infected with the delta variant were younger (mean age = 35years vs 39 years for alpha, p<0.001) and had lesser vaccination coverage (54% vs 72% for alpha, p<0.001). RT-PCR Ct values were similar for both variants at the baseline test; however by the fourth test, delta variant patients had significantly lower Ct values (27 vs 29, p=0.05). Length of hospital stay was higher in delta variant patients in vaccinated (3 days vs 2.9 days for alpha variant) as well as in unvaccinated patients (5.2 days vs 4.4 days for alpha variant, p<0.001). Hazards of hospital discharge after adjusting for vaccination status, age, and sex was higher for alpha variant infections (HR=1.2, 95% CI: 1.01-1.41, p=0.029). Conclusion: Patients infected with the delta variant of SARS-CoV-2 were found to have a slower recovery as indicated by longer length of stay and higher shedding of the virus compared to alpha variant infections, and this trend was consistent in both vaccinated and unvaccinated patients.

Is glucose-6-phosphatase dehydrogenase deficiency associated with severe outcomes in hospitalized COVID-19 patients?

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is known to suppress the antioxidant system and is likely to aggravate severity of COVID-19, which results in a pro-oxidant response. This possible association has not been explored adequately in human studies. In this research, we report that the occurrence of non-invasive ventilation, intubation or death-all of which are indicative of severe COVID-19, are not significantly different in hospitalized COVID-19 patients with and without G6PDd (4.6 vs. 6.4%, p = 0.33). The likelihood of developing any of these severe outcomes were slightly lower in patients with G6PDd after accounting for age, nationality, presence of comorbidities and drug interventions (Odds ratio 0.40, 95% confidence intervals 0.142, 1.148). Further investigation that extends to both, hospitalized and non-hospitalized COVID-19 patients, is warranted to study this potential association.

The effect of ABO blood group and antibody class on the risk of COVID-19 infection and severity of clinical outcomes.

The COVID-19 pandemic has affected more than 100 million cases and caused immense burdens on governments and healthcare systems worldwide. Since its emergence in December 2019, research has been focused on treating the infected, identifying those at risk and preventing spread. There is currently no known biological biomarker that predicts the risk of infection. Several studies emerged suggesting an association between ABO blood group and the risk of COVID-19 infection. In this study, we used retrospective observational data in Bahrain to investigate the association between ABO blood group and risk of infection, as well as susceptibility to severe ICU-requiring infection. We found a higher risk associated with blood group B, and a lower risk with blood group AB. No association was observed between blood group and the risk of a severe ICU-requiring infection. We extended the analysis to study the association by antibodies; anti-a (blood groups B and O) and anti-b (blood groups A and O). No association between antibodies and both risk of infection or susceptibility to severe infection was found. The current study, along with the variation in blood group association results, indicates that blood group may not be an ideal biomarker to predict risk of COVID-19 infection.

The Efficacy and Safety of Hydroxychloroquine in Patients with COVID-19: A Multicenter National Retrospective Cohort.

INTRODUCTION: Hydroxychloroquine (HCQ) is an antimalarial drug that received worldwide news and media attention in the treatment of patients with coronavirus disease 2019 (COVID-19). This drug was used on the basis of its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using HCQ in treatment of patients with COVID-19 who were admitted in acute care hospitals in Bahrain. METHODS: We conducted a retrospective cohort study on a random sample of patients admitted with COVID-19 between 24 February and 31 July 2020. The study was conducted in four acute care COVID-19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation, or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression, and matched propensity score analysis. RESULTS: A random sample of 1571 patients were included, 440 of whom received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43, 95% CI 0.85-2.37, P = 0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7, 95% CI 0.82-8.85, P = 0.10). HCQ was associated with increased risk of hypoglycemia (OR 10.9, 95% CI 1.72-69.49, P = 0.011) and diarrhea (OR 2.8, 95% CI 1.4-5.5, P = 0.003), but not QT prolongation (OR 1.92, 95% CI 0.95-3.9, P = 0.06) or cardiac arrhythmia (OR 1.06, 95% CI 0.55-2.05, P = 0.85). CONCLUSION: Our results showed no significant beneficial effect of using hydroxychloroquine on the outcome of patients with COVID-19. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out-of-hospital use.

Quarantining arriving travelers in the era of COVID-19: balancing the risk and benefits a learning experience from Bahrain.

The quarantine period imposed to travelers in many countries due to COVID19 is a major obstacle for any traveler. Lifting the quarantine period could lead to significant improvement in people's quality of life and any country's economy. Bahrain have used two quarantine models from arriving passengers. We report data about the incidence of COVID19 on arriving passengers at Bahrain International airport. Infection rates were reported on arrival, during quarantine and after leaving quarantine. Results showed that travelers had low incidence of COVID19 on arriving and during the quarantine period, while becoming at higher risk after leaving quarantine. We concluded that quarantine requirement maybe lifted for arriving travelers. Testing upon arrival with implementation of the public health preventative measures can minimize the risk of transmission.

Self-limited focal epilepsy and childhood apraxia of speech with WAC pathogenic variants.

Heterozygous pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures are reported in one quarter, including tonic-clonic, absence, and febrile seizures. This study aimed to better understand the phenotypic spectrum of epilepsy and development in Desanto-Shinawi syndrome. We identified four children with seizures and pathogenic WAC variants, including two siblings. All had global developmental impairment with language affected most severely; two had diagnoses of childhood apraxia of speech and two had autism spectrum disorder. Seizure onset age ranged from six months to 14 years. Seizures always occurred from sleep and were focal impaired awareness with motor features in three patients, with one having bilateral tonic-clonic seizures of suspected focal onset. Two patients had spontaneous seizure resolution without treatment, and the remaining two were well-controlled on monotherapy. EEG was normal in two patients; one had focal right frontal spikes in drowsiness and sleep while the last had independent centrotemporal spikes from both hemispheres, activated in sleep. All patients had heterozygous truncating pathogenic WAC variants, with negative parental testing. The findings in this cohort of patients suggest that epilepsy in Desanto-Shinawi syndrome is usually focal and self-limited, and may fall within the epilepsy-aphasia spectrum.

Evaluation of Rapid Antigen Tests Using Nasal Samples to Diagnose SARS-CoV-2 in Symptomatic Patients.

INTRODUCTION: The best way to mitigate an outbreak besides mass vaccination is via early detection and isolation of infected cases. As such, a rapid, cost-effective test for the early detection of COVID-19 is required. METHODS: The study included 4,183 mildly symptomatic patients. A nasal and nasopharyngeal sample obtained from each patient was analyzed to determine the diagnostic ability of the rapid antigen detection test (RADT, nasal swab) in comparison with the current gold-standard (RT-PCR, nasopharyngeal swab). RESULTS: The calculated sensitivity and specificity of the RADT was 82.1 and 99.1%, respectively. Kappa's coefficient of agreement between the RADT and RT-PCR was 0.859 (p < 0.001). Stratified analysis showed that the sensitivity of the RADT improved significantly when lowering the cut-off RT-PCR Ct value to 24. CONCLUSION: Our study's results support the potential use of nasal swab RADT as a screening tool in mildly symptomatic patients, especially in patients with higher viral loads.

Association between RT-PCR Ct values and COVID-19 new daily cases: a multicenter cross-sectional study.

Proactive prediction of the epidemiologic dynamics of viral diseases and outbreaks of the type of COVID-19 has remained a difficult pursuit for scientists, public health researchers, and policymakers. It is unclear whether RT-PCR Cycle Threshold (Ct) values of COVID-19 - or any other virus - as indicator of viral load, could represent a possible predictor for underlying epidemiologic changes on a population level. The study objective is thus to investigate whether population-wide changes in SARS-CoV-2 RT-PCR Ct values over time are associated with the daily fraction of positive COVID-19 tests. In addition, this study analyses the factors that could influence RT-PCR Ct values. A retrospective cross-sectional study was conducted on 63,879 patients from May 4, 2020 to September 30, 2020, in all COVID-19 facilities in the Kingdom of Bahrain. Data collected included number of tests and newly diagnosed cases, as well as Ct values, age, sex nationality, and symptomatic status. Ct values were found to be negatively and very weakly correlated with the fraction of daily positive tests in the population r = -0.06 (CI 95%: -0.06; -0.05; p=0.001). The R-squared for the regression model (adjusting for age and number of daily tests) showed an accuracy of 45.3%. Ct Values showed an association with nationality (p=0.012). After the stratification, the association between Ct values and the fraction of daily positive cases was only maintained for the female sex and Bahraini-nationality. Symptomatic presentation was significantly associated with lower Ct values (higher viral loads). Ct values do not show any correlation with age (p=0.333) or sex (p=0.522). We report one of the first and largest studies to investigate the epidemiologic associations of Ct values with COVID-19. Although changes in Ct values showed a moderate association with daily cases, our results indicate that it may not be as predictive within a simple model. More population studies and models from global cohorts are necessary.

Lateral Medullary Syndrome Due to Left Vertebral Artery Occlusion in a Boy Postflexion Neck Injury.

Lateral medullary syndrome is rare in pediatrics. It is characterized by neurological deficits due to an ischemic lesion in the lateral medulla. The authors describe a 17-year-old boy who developed lateral medullary syndrome in the context of a hyperflexion neck injury while diving in shallow water with traumatic vascular injury. He had "crossed" neurological deficits above and below the neck. His magnetic resonance angiography showed intra- and extracranial left vertebral artery occlusion and his magnetic resonance imaging showed signal abnormality involving the left lateral medulla and inferomedial cerebellum in keeping with an infarct secondary to left vertebral artery and left posterior inferior cerebellar artery occlusion. Good neurological recovery was observed on heparin therapy started after surgical treatment of traumatic injury. To our knowledge, this is the first reported case of lateral medullary syndrome in a pediatric population related to a flexion neck injury. The authors emphasize the importance of a high level of suspicion for accurate diagnosis.

Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant.

BACKGROUND: Acute hemorrhagic encephalomyelitis (AHEM) is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome. OBJECTIVE: To report the association with Ran Binding Protein (RANBP2) gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP) in life-threatening AHEM. DESIGN: Single case study. CASE REPORT: A 6-year-old girl known to have sickle cell disease (SCD) presented an acquired demyelinating syndrome (ADS) with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day). Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG). She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu) was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells. CONCLUSION: In any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom with IVMP. This case report, in addition to others, stresses the likely efficacy of combined craniotomy, IVIG, and IVMP treatments in AHEM. RANBP2 mutations may sensitize the brain to inflammation and predispose to AHEM.