Clinical Characteristics, Laboratory Findings, Management, and Outcome of Severe Coronavirus Disease 2019 in Children at a Tertiary Care Center in Riyadh, Saudi Arabia: A Retrospective Study.

Background: Numerous studies worldwide have reported COVID-19 in children; however, the clinical symptoms and consequences of COVID-19 in children have only been reported in a few studies in Saudi and gulf region. Therefore, we aimed to investigate the clinical features and outcomes of COVID-19 infection in children and the therapeutic interventions used. Methods: This retrospective cohort study included 96 patients with confirmed severe acute respiratory syndrome coronavirus 2 infection aged ≤14 years who were admitted to a tertiary governmental care hospital in Riyadh, Saudi Arabia between March 2020 and November 2020. Data on children with COVID-19, including demographics, comorbidities, symptoms, imaging and laboratory results, therapies, and clinical outcomes, were analyzed. Results: Of 96 children admitted with a confirmed diagnosis of COVID-19, 63.8% were aged ≤ 3 years, 52.1% were male, 56.2% had an unknown source of infection, and 51% had no comorbidities. Most cases had severe infection (71.88%) as they required oxygen, 10.42% of whom were critical. The most common symptoms were respiratory-related (98%), and the common physical sign was fever (49%). High D-dimer (90.7%) and C-reactive protein (72.09%) levels were found in most cases. Oxygen (71.88%) was the most commonly used treatment. Most patients were discharged home and fully recovered (97.92%). We reported two deaths (2.08%). Conclusions: Our findings showed that the majority of the admitted children with COVID-19 were ≤3 years of age (52.1%) and infected with an unknown source (56.2%). Moreover, the majority of the cases had severe COVID-19 infection as they required oxygen (71.88%), although they had favorable outcomes. However, some cases were critical and resulted in death. Future studies will be crucial to better understand the disease spectrum and potential therapeutic options for COVID-19 in children.

Willingness, beliefs, and barriers regarding the COVID-19 vaccine in Saudi Arabia: a multiregional cross-sectional study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread worldwide, and the vaccine remains the ultimate cornerstone to overcoming its long-term impact. Vaccine hesitancy might obstruct the effort to achieve herd immunity and eradicate the virus. We assessed Saudi Arabian individuals' willingness, beliefs, and barriers regarding the COVID-19 vaccine and their adherence to preventive measures during and after the pandemic. METHODS: A self-administered electronic validated questionnaire was distributed among the five major regions in Saudi Arabia between November and December 2020. The questionnaire addressed the sociodemographic data, beliefs, potential barriers, parents' acceptance of COVID-19 vaccination for their children, and adherence to protective measures during and after the pandemic. RESULTS: Of 8,056 participants, 4,218 (52.4%) of a non-representative sample were willing to be vaccinated against COVID-19. Being a young adult, male, having less than a high school degree, being a smoker, having a chronic disease, and having a history of seasonal influenza vaccine uptake were positive predictors of COVID-19 vaccine acceptance. Hesitant participants reported concerns about vaccine side effects and safety as the main barriers to accepting the COVID-19 vaccine. Some refusers (26.1%) declared that they would reconsider vaccination only if the safety and effectiveness of the vaccine were reported by more studies. CONCLUSIONS: Our study revealed a promising willingness to accept the vaccine among the population, with positive beliefs and attitudes toward COVID-19 vaccination. However, a considerable proportion of the population was reluctant to accept the vaccine. Thus, publicly providing information about vaccine safety and implementing health education programs is crucial for increasing the public's confidence in the vaccine.

Causes of Hospitalization for Systemic Lupus Erythematosus in Saudi Arabia Compared With the Global Setting: A Retrospective Single-center Observational Study.

BACKGROUND: This study sought to evaluate the main causes of hospitalization of patients with systemic lupus erythematosus (SLE) in a tertiary health center in Saudi Arabia. METHODS: A retrospective observational study was performed for all the SLE patients admitted to King Saud Medical City between 2016 and 2019. The primary reason for hospitalization was determined by the primary physician caring for the patient at the time of admission. RESULTS: Of the 98 hospitalizations for SLE, 49% of patients were admitted from the emergency department (ED) and 51% from the rheumatology clinic. The most common reason for hospitalization was lupus flare (68.4%) followed by infection (20.4%). The lupus flare patients commonly presented with musculoskeletal (MSK)symptoms (34.6%), renal manifestations (25.5%), and skin rash (24.5%), whereas patients admitted with infection were commonly diagnosed with community-acquired pneumonia (12.2%). Other hospitalization causes were obstetric complications, adverse drug reactions, and thrombosis. Intensive care unit (ICU) admission was necessary for 7% of patients due to acute respiratory distress syndrome (ARDS) and pulmonary hemorrhage (28.6%) or other reasons (14.1%), such as pleural effusion, cardiac tamponade, and thrombotic thrombocytopenic purpura (TTP). Conclusions: The two most common reasons for SLE hospitalization were lupus flare and infection. Lupus flare was mainly due to MSK, renal, and dermatologic manifestations. The most common infection leading to hospitalization was community-acquired pneumonia, and ICU admission was mainly due to ARDS and pulmonary hemorrhage.

Landscape of somatic mutations in breast cancer: new opportunities for targeted therapies in Saudi Arabian patients.

Breast cancer (BCa) ranks first in incidence rate among cancers in Arab females. The association between genetic polymorphisms in tumor suppressor genes and the risk of BCa has been studied in many ethnic populations with conflicting conclusions while Arab females and Saudi Arabian studies are still lacking. We screened a cohort of Saudi BCa patients by NGS using a bespoke gene panel to clarify the genetic landscape of this population, correlating and assessing genetic findings with clinical outcomes. We identified a total of 263 mutations spanning 51 genes, including several frequently mutated. Among the genes analyzed, the highest mutation rates were found in PIK3CA (12.9%), BRCA2 (11.7%), BRCA1 (10.2%), TP53 (6.0%), MSH2 (3.8%), PMS2 (3.8%), BARD1 (3.8%), MLH1 (3.4%), CDH1 (3.0%), RAD50 (3.0%), MSH6 (3.0%), NF1 (2.6%), in addition to others. We identified multiple common recurrent variants and previously reported mutations. We also identified 46 novel variants in 22 genes that were predicted to have a pathogenic effect. Survival analysis according to the four most common mutations (BRCA1, BRCA2, TP53, and PIK3CA) showed reduced survival in BRCA1 and BRCA2-mutant patients compared to total patients. Moreover, BRCA2 was demonstrated as an independent predictor of reduced survival using independent Cox proportional hazard models. We reveal the landscape of the mutations associated with BCa in Saudi women, highlighting the importance of routine genetic sequencing in implementation of precision therapies in KSA.

Methylation Profiling of Medulloblastoma in a Clinical Setting Permits Sub-classification and Reveals New Outcome Predictions.

Medulloblastoma (MB) is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, but assessments in Saudi Arabian (SA)-MB cases are sparse. MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3), and Group 4 (G4) tumors. The WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signaling, whilst G3/G4 tumors show recurrent chromosomal alterations. Given that each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. Here, we performed the first assessment of MB-DNA methylation patterns in an SA cohort using archival biopsy material (FPPE n = 49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3, and G4). Furthermore, methylation analysis was able to reclassify tumors that could not be sub-grouped through next-generation sequencing, highlighting its superior accuracy for MB molecular classifications. Independent assessments demonstrated known clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates, and a large number of tumor-associated deaths. Taking our results together, we demonstrate that DNA methylation profiling enables the robust sub-classification of four disease sub-groups in archival FFPE biopsy material from SA-MB patients. Moreover, we show that the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.

Posttranslational modifications of apolipoprotein A-II proteoforms in type 2 diabetes.

BACKGROUND: Apolipoprotein A-II (apoA-II) is the second most abundant protein in high-density lipoprotein particles. However, it exists in plasma in multiple forms. The effect of diabetes on apoA-II proteoforms is not known. OBJECTIVE: Our objective was to characterize plasma apoA-II proteoforms in participants with and without type 2 diabetes. METHODS: Using a novel mass spectrometric immunoassay, the relative abundance of apoA-II proteoforms was examined in plasma of 30 participants with type 2 diabetes and 25 participants without diabetes. RESULTS: Six apoA-II proteoforms (monomer, truncated TQ monomer, truncated Q monomer, dimer, truncated Q dimer, and truncated 2Qs dimer) and their oxidized proteoforms were identified. The ratios of oxidized monomer and all oxidized proteoforms to the native apoA-II were significantly greater in the diabetic group (P = .004 and P = .005, respectively) compared with the nondiabetic group. CONCLUSION: The relative abundance of oxidized apoA-II is significantly increased in type 2 diabetes.

The association of plasma cystatin C proteoforms with diabetic chronic kidney disease.

BACKGROUND: Cystatin C (CysC) is an endogenous cysteine protease inhibitor that can be used to assess the progression of kidney function. Recent studies demonstrate that CysC is a more specific indicator of glomerular filtration rate (GFR) than creatinine. CysC in plasma exists in multiple proteoforms. The goal of this study was to clarify the association of native CysC, CysC missing N-terminal Serine (CysC des-S), and CysC without three N-terminal residues (CysC des-SSP) with diabetic chronic kidney disease (CKD). RESULTS: Using mass spectrometric immunoassay, the plasma concentrations of native CysC and the two CysC truncation proteoforms were examined in 111 individuals from three groups: 33 non-diabetic controls, 34 participants with type 2 diabetes (DM) and without CKD and 44 participants with diabetic CKD. Native CysC concentrations were 1.4 fold greater in CKD compared to DM group (p = 0.02) and 1.5 fold greater in CKD compared to the control group (p = 0.001). CysC des-S concentrations were 1.55 fold greater in CKD compared to the DM group (p = 0.002) and 1.9 fold greater in CKD compared to the control group (p = 0.0002). CysC des-SSP concentrations were 1.8 fold greater in CKD compared to the DM group (p = 0.008) and 1.52 fold greater in CKD compared to the control group (p = 0.002). In addition, the concentrations of CysC proteoforms were greater in the setting of albuminuria. The truncated CysC proteoform concentrations were associated with estimated GFR independent of native CysC concentrations. CONCLUSION: Our findings demonstrate a greater amount of CysC proteoforms in diabetic CKD. We therefore suggest assessing the role of cystatin C proteoforms in the progression of CKD.