Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study.

OBJECTIVES: To investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE). METHODS: A retrospective observational analytical study analysed data from 738 medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity. RESULTS: Main risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653-46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905). CONCLUSION: Identifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Incidence and risk factors of prostate cancer among the Northern and Eastern parts of the United Arab Emirates population.

BACKGROUND: Prostate cancer (PCa) is a prevalent disease worldwide. However, the incidence and patient-specific risk factors of PCa in the Middle East, specifically in the United Arab Emirates, have not been previously reported. METHODS: We conducted a retrospective cohort study on 2377 men diagnosed with either benign prostatic hyperplasia (BPH) or PCa in the Northern and Eastern regions of the United Arab Emirates, excluding the Western part, which includes Abu Dhabi. The study spanned from January 2012 and December 2021. To calculate the PCa incidence rate, we utilized the world age-standardized incidence rates (W-ASIR) categorized by age groups. Patient-specific risk factors of PCa were identified through a multivariate logistic regression analysis of clinical data. RESULTS: A total of 247 cases of PCa and 2130 cases of BPH were included in the study. In our cohort, the W-ASIR for PCa was 21.3 per 100,000 men. The incidence of PCa showed an increasing trend with age, with the highest incidence observed among men aged 70 years and older. Accordingly, multivariate analysis revealed that age over 70 was associated with an increased risk of PCa (OR: 2.546, 95% confidence interval [CI]: 1.892-3.425, p < 0.01). On the other hand, preexisting conditions such as hypertension and diabetes mellitus were found to lower the risk of PCa (OR: 0.222, 95% CI: 0.163-0.302, p < 0.001) and (OR: 0.364, 95% CI: 0.205-0.648, p < 0.001), respectively. Additionally, metformin intake was associated with a reduced risk of PCa (OR: 0.385, 95% CI: 0.190-0.782, p = 0.008); while insulin usage increased the risk of PCa (OR: 2.586, 95% CI: 1.539-4.344, p < 0.001). Anti-BPH medications such as phosphodiesterase inhibitors (OR: 0.223, 95% CI: 0.069-0.723, p = 0.012) or 5-α reductase (OR: 0.206, 95% CI: 0.110-0.389, p < 0.000), were found to lower the risk of PCa. CONCLUSION: The findings underscore the high incidence of PCa in the United Arab Emirates, with age being a significant factor. Furthermore, the study highlights the influence of certain comorbidities and medications on the risk of developing PCa within the United Arab Emirates population.

Cell free ACE2 RNA: A potential biomarker of COVID-19 severity.

Despite the downward trend of COVID-19 pandemic and increased immunity of the general population, COVID-19 is still an elusive disease with risks due to emerging variants. Fast and reliable diagnosis of COVID-19 disease would allow better therapeutic interventions for patients at risk to develop more severe outcomes. Cell-free RNAs (cfRNAs) have been proven to be an effective biomarker in cancer and infectious diseases. It has been reported that cfRNAs are amplified in the bloodstream of these patients and at earlier stages of the disease, reflecting tissue damage. Hence, we hypothesize that cfRNAs may serve as a potential indicator of COVID-19 disease severity. To our knowledge, this is the first report to display a significant link between COVID-19 severity and cfRNA of angiotensin converting enzyme-2 (ACE2), the receptor for SARS-CoV-2 virus. qRT-PCR analysis of liquid biopsies from COVID-19 patients (n = 82) displayed a significant increase in ACE2-cfRNA levels in patients with severe manifestations. This finding correlated with blood biomarkers (ANC, WBC, and Creatinine) that were also significantly increased in these patients. We previously showed that bronchial cells from obese subjects express higher ACE2 levels, hence, we further analysed the involvement of obesity as a main contributor to severe outcomes. We confirm a significant increase of ACE2-cfRNA in the plasma of obese/overweight (Ob/Ov) COVID-19 patients compared to lean subjects, with no observed significant change in blood biomarkers. These findings suggest that monitoring ACE2-cfRNAs, as a biomarker, during COVID-19 infection may allow for better disease management, specifically for severe-COVID-19 patients.

Assessing the Link between Diabetic Metabolic Dysregulation and Breast Cancer Progression.

Diabetes mellitus is a burdensome disease that affects various cellular functions through altered glucose metabolism. Several reports have linked diabetes to cancer development; however, the exact molecular mechanism of how diabetes-related traits contribute to cancer progression is not fully understood. The current study aimed to explore the molecular mechanism underlying the potential effect of hyperglycemia combined with hyperinsulinemia on the progression of breast cancer cells. To this end, gene dysregulation induced by the exposure of MCF7 breast cancer cells to hyperglycemia (HG), or a combination of hyperglycemia and hyperinsulinemia (HGI), was analyzed using a microarray gene expression assay. Hyperglycemia combined with hyperinsulinemia induced differential expression of 45 genes (greater than or equal to two-fold), which were not shared by other treatments. On the other hand, in silico analysis performed using a publicly available dataset (GEO: GSE150586) revealed differential upregulation of 15 genes in the breast tumor tissues of diabetic patients with breast cancer when compared with breast cancer patients with no diabetes. SLC26A11, ALDH1A3, MED20, PABPC4 and SCP2 were among the top upregulated genes in both microarray data and the in silico analysis. In conclusion, hyperglycemia combined with hyperinsulinemia caused a likely unique signature that contributes to acquiring more carcinogenic traits. Indeed, these findings might potentially add emphasis on how monitoring diabetes-related metabolic alteration as an adjunct to diabetes therapy is important in improving breast cancer outcomes. However, further detailed studies are required to decipher the role of the highlighted genes, in this study, in the pathogenesis of breast cancer in patients with a different glycemic index.

Nucleic acid sensor STING drives remodeling and its inhibition enhances steroid responsiveness in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often associated with double-stranded DNA release which potentially activates DNA-sensing pathways, such as STING. This study, therefore, analyzed the role of STING pathway in inducing pulmonary inflammation, steroid resistance, and remodeling in COPD. METHODS: Primary cultured lung fibroblasts were isolated from healthy non-smoker, healthy smoker, and smoker COPD individuals. The expression of STING pathway, remodeling, and steroid resistance signatures were investigated in these fibroblasts upon LPS stimulation and treatment with dexamethasone and/or STING inhibitor, at both mRNA and protein levels using qRT-PCR, western blot, and ELISA. RESULTS: At baseline, STING was elevated in healthy smoker fibroblasts and to a higher extent in smoker COPD fibroblasts when compared to healthy non-smoker fibroblasts. Upon using dexamethasone as monotherapy, STING activity was significantly inhibited in healthy non-smoker fibroblasts but showed resistance in COPD fibroblasts. Treating both healthy and COPD fibroblasts with STING inhibitor in combination with dexamethasone additively inhibited STING pathway in both groups. Moreover, STING stimulation triggered a significant increase in remodeling markers and a reduction in HDAC2 expression. Interestingly, treating COPD fibroblasts with the combination of STING inhibitor and dexamethasone alleviated remodeling and reversed steroid hyporesponsiveness through an upregulation of HDAC2. CONCLUSION: These findings support that STING pathway plays an important role in COPD pathogenesis, via inducing pulmonary inflammation, steroid resistance, and remodeling. This raises the possibility of using STING inhibitor as a potential therapeutic adjuvant in combination with common steroid treatment.

Molecular pathogenicity of 1-nonadecene and L-lactic acid, unique metabolites in radicular cysts and periapical granulomas.

Recently, 1-nonadecene and L-lactic acid were identified as unique metabolites in radicular cysts and periapical granuloma, respectively. However, the biological roles of these metabolites were unknown. Therefore, we aimed to investigate the inflammatory and mesenchymal-epithelial transition (MET) effects of 1-nonadecene, and the inflammatory and collagen precipitation effects of L-lactic acid on both periodontal ligament fibroblasts (PdLFs) and peripheral blood mononuclear cells (PBMCs). PdLFs and PBMCs were treated with 1-nonadecene and L-lactic acid. Cytokines' expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). E-cadherin, N-cadherin, and macrophage polarization markers were measured using flow cytometry. The collagen, matrix metalloproteinase (MMP)-1, and released cytokines were measured using collagen assay, western blot, and Luminex assay, respectively. In PdLFs, 1-nonadecene enhances inflammation through the upregulation of some inflammatory cytokines including IL-1ß, IL-6, IL-12A, monocyte chemoattractant protein (MCP)-1, and platelet-derived growth factor (PDGF) α. 1-Nonadecene also induced MET through the upregulation of E-cadherin and the downregulation of N-cadherin in PdLFs. 1-Nonadecene polarized macrophages to a pro-inflammatory phenotype and suppressed their cytokines' release. L-lactic acid exerted a differential impact on the inflammation and proliferation markers. Intriguingly, L-lactic acid induced fibrosis-like effects by enhancing collagen synthesis, while inhibiting MMP-1 release in PdLFs. These results provide a deeper understanding of 1-nonadecene and L-lactic acid's roles in modulating the microenvironment of the periapical area. Consequently, further clinical investigation can be employed for target therapy.

Risks of prostate cancer and mortality in the city of Sharjah, United Arab Emirates.

Background: Prostatic hyperplasia (BPH) and prostate cancer (PCa) are common age-related diseases in men. According to World Health Organization (WHO), PCa is the second most common cancer among Emirati men. This study aimed to identify the risk factors associated with PCa and mortality in a cohort diagnosed with PCa between 2012 and 2021 in Sharjah, United Arab Emirates (UAE). Methods: The data collected in this retrospective case-control study included patient demographics and comorbidities, as well as PCa markers such as prostate-specific antigen (PSA), prostate volume, prostate-specific antigen density (PSAD), and Gleason scores. Risk factors for PCa were assessed using multivariate logistic regression analysis, and factors associated with all-cause mortality in PCa patients were evaluated using Cox-proportional hazard analysis. Results: Of the 192 cases analyzed in this study, 88 were diagnosed with PCa and 104 were diagnosed with BPH. Regarding risk factors for PCa, a higher risk of PCa was associated with age 65 or older (OR=2.76, 95% confidence interval (CI): 1.04-7.30; P=0.038) and serum PSAD greater than 0.1 ng/mL2 (OR=3.48, 95% CI:1.66-7.32; P=0.001), whereas being of UAE nationals (OR=0.40, 95% CI:0.18-0.88; P=0.029) were associated with lower risk of PCa, after adjusting for patient demographics and comorbidities. Moreover, regarding cancer markers, higher serum PSA level (P=0.003) and smaller prostate volume (P=0.028) were associated with a higher risk of PCa, after adjusting with patients' age and BMI. Additionally, a high-grade Gleason score was associated with an increased risk of all-cause mortality after adjusting for patient's age and BMI (hazard ratio, aHR= 2.3, 95% CI:1.3-4.1; P= 0.016). Conclusion: This study found that age 65 or older and serum PSAD greater than 0.1 ng/mL2 are risk factors for PCa, while UAE nationality is associated with a lower risk. PSAD may be a better screening marker for PCa compared to traditional markers such as PSA and prostate volume.

The Essential Role of 17-Octadecynoic Acid in the Pathogenesis of Periapical Abscesses.

INTRODUCTION: Periapical abscesses are 1 of the most frequent pathologic lesions in the alveolar bone. Recently, we have identified 17-octadecynoic acid (17-ODYA) as the highest unique metabolite in periapical abscesses. Therefore, the aim of this study was to investigate the immunologic and pathophysiological roles of this metabolite in the initiation and development of periapical abscesses. METHODS: Periodontal ligament fibroblasts and peripheral blood mononuclear cells were treated with 17-ODYA. Gene expression analysis and interleukin (IL)-8 release were determined using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophage polarization and cytokine release were also determined using flow cytometry and Luminex bioassay (R&D Systems, Minneapolis, MN), respectively. RESULTS: In periodontal ligament fibroblasts, 17-ODYA caused significant (P < .0001) up-regulation of IL-1α, IL-1ß, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 µmol/L after 6 days of treatment and up-regulation of platelet-derived growth factor alpha and vascular endothelial growth factor alpha at all tested concentrations after 2 days of treatment. In peripheral blood mononuclear cells, 17-ODYA significantly increased the expression of IL-1α, IL-1ß, IL-6, matrix metalloproteinase-1, and monocyte chemoattractant protein-1 at 10 µmol/L (P < .0001) and vascular endothelial growth factor alpha and platelet-derived growth factor alpha at 1 µmol/L 17-ODYA (P < .0001). 17-ODYA polarized macrophages toward a proinflammatory phenotype (M1) and suppressed the release of pro- and anti-inflammatory cytokines. 17-ODYA significantly enhanced the release of IL-8. CONCLUSIONS: This study was the first to identify the pathologic role of 17-ODYA in the development of periapical abscesses. The results of this study are important in shedding light on the pathogenesis of periapical abscesses in relation to microbial metabolites.

Vitamin D modulates systemic inflammation in patients with severe COVID-19.

AIMS: The ability of vitamin D (VitD) to modulate immune responses in the clinical setting of COVID-19 infection is not well investigated. This study aimed to evaluate the ability of VitD to attenuate inflammatory responses in patients with severe COVID-19. MATERIALS AND METHODS: Blood samples and nasopharyngeal swabs were obtained from patients with severe COVID-19 who had been treated (20 patients), or not (25 patients), with VitD, during their stay in the intensive care unit. Western blotting was used to evaluate the expressions of STAT3, JNK and AKT signaling pathways and ELISA was used to measure levels of IL-6, IL-17, and IL-1ß in blood of these patients. KEY FINDINGS: Reduced levels of STAT3, JNK and AKT pathways and lower levels of proinflammatory cytokines such as IL-6, IL-17, and IL-1ß were observed in VitD treated patients (50,000 IU of cholecalciferol weekly for 3 weeks), and in vitro following treatment of poly I:C stimulated PBMCs with VitD (50 nM of calcitriol). Moreover, lower circulatory levels of these proinflammatory cytokines following treatment with VitD were associated with lower serum levels of COVID-19-related severity markers such as D-dimer and C-reactive proteins (P < 0.001) which in overall resulted in shorter length of ICU stay for VitD treated compared to untreated patients (18 days for VitD treated vs. 28 days for VitD untreated; P = 0.01). SIGNIFICANCE: This study reveals that VitD plays immunomodulatory role during COVID-19 infection, which further emphasizes the importance of maintaining a normal level of this vitamin for the prevention of hyperinflammatory conditions associated with COVID-19.

Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome.

Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.

SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis.

AIMS: Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague. MAIN METHODS: GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay. KEY FINDINGS: Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r2 = 0.238, P = 0.006), EPO (r2 = 0.18, P = 0.01) and EGF (r2 = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r2 = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r2 = 0.199, P = 0.01), EPO (r2 = 0.115, P = 0.02), and EGF (r2 = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin. SIGNIFICANCE: Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.

TFPI and FXIII negatively and S100A8/A9 and Cystatin C positively correlate with D-dimer in COVID-19.

D-dimer is an established biomarker of thromboembolism and severity in COVID-19. We and others have recently reported the dysregulation of tissue factor pathway inhibitor (TFPI), FXIII, fibrinolytic pathway, inflammatory markers, and tissue injury markers, particularly in severe COVID-19. However, association of these markers with thromboembolism in COVID-19 remains elusive. The correlation analyses between these markers in patients with moderate (non-ICU) and severe COVID-19 (ICU) were performed to delineate the potential pathomechanisms and impact of thromboembolism. We observe a negative correlation of plasma TFPI (r2 = 0.148, P = 0.035), FXIII (r2 = 0.242, P = 0.006), and plasminogen (r2 = 0.27, P = 0.003) with D-dimer, a biomarker of thromboembolism, levels in these patients. Further analysis revealed a strong positive correlation between fibrinolytic markers tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) (r2 = 0.584, P < 0.0001). Interestingly, a significant positive correlation of PAI-1, but not tPA, was observed with platelets and endothelial cells dysfunction markers P-selectin (r2 = 0.184, P = 0.01) and soluble CD40 ligand (sCD40 L) (r2 = 0.163, P = 0.02). Moreover, calprotectin (S100A8/A9) and cystatin C (CST3), previously linked with thromboembolism, exhibited positive correlations with each other (r2 = 0.339, P = 0.0007) and with the level of D-dimer independently in COVID-19. Finally, the tissue injury marker myoglobin demonstrated a strong positive correlation with D-dimer (r2 = 0.408, P = 0.0001). Taken together, inverse correlations of TFPI and FXIII with D-dimer suggest the TF pathway activation and aberrant fibrin polymerization in COVID-19 patients. The elevated level of PAI-1 is potentially contributed by activated platelets and endothelial cells. S100A8/A9 may also play roles in impaired fibrinolysis and thromboembolism, in part, through regulating the CST3. These findings strengthen the understanding of thromboembolism and tissue injury and may help in better management of thromboembolic complications in COVID-19 patients.

Lipocalin-2, S100A8/A9, and cystatin C: Potential predictive biomarkers of cardiovascular complications in COVID-19.

Severe coronavirus (SARS-COV-2) infection often leads to systemic inflammation accompanied by cardiovascular complications including venous thromboembolism (VTE). However, it is largely undefined if inflammatory markers such as lipocalin-2 (LNC2), calprotectin (S100A8/A9), and cystatin C (CST3), previously linked with VTE, play roles in cardiovascular complications and advancement of COVID-19 severity. To investigate the same, hospitalized moderate and severe (presented pneumonia and required intensive care) COVID-19 patients were recruited. The levels of plasma LNC2, S100A8/A9, CST3, myoglobin, and cardiac Troponin I (cTnI) were assessed through enzyme-linked immunosorbent assay (ELISA). The investigation revealed a significantly upregulated level of plasma LNC2 at the moderate stage of SARS-CoV-2 infection. In contrast, the levels of S100A8/A9 and CST3 in moderate patients were comparable to healthy controls; however, a profound induction was observed only in severe COVID-19 patients. The tissue injury marker myoglobin was unchanged in moderate patients; however, a significantly elevated level was observed in the critically ill COVID-19 patients. In contrast, cTnI level was unchanged both in moderate and severe patients. Analysis revealed a positive correlation between the levels of S100A8/A9 and CST3 with myoglobin in COVID-19. In silico analysis predicted interactions of S100A8/A9 with toll-like receptor 4 (TLR-4), MyD88 LY96, and LCN2 with several other inflammatory mediators including MMP2, MMP9, TIMP1, and interleukins (IL-6, IL-17A, and IL-10). In summary, early induction of LCN2 likely plays a role in advancing the COVID-19 severity. A positive correlation of S100A8/A9 and CST3 with myoglobin suggests that these proteins may serve as predictive biomarkers for thromboembolism and tissue injury in COVID-19.

Long term predictors of breathlessness, exercise intolerance, chronic fatigue and well-being in hospitalized patients with COVID-19: A cohort study with 4 months median follow-up.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is an emerging healthcare burden. We therefore aimed to determine predictors of different functional outcomes after hospital discharge in patients with COVID-19. METHODS: An ambidirectional cohort study was conducted between May and July 2020, in which PCR-confirmed COVID-19 patients underwent a standardized telephone assessment between 6 weeks and 6 months post discharge. We excluded patients who died, had a mental illness or failed to respond to two follow-up phone calls. The medical research council (MRC) dyspnea scale, metabolic equivalent of task (MET) score for exercise tolerance, chronic fatigability syndrome (CFS) scale and World Health Organization-five well-being index (WHO-5) for mental health were used to evaluate symptoms at follow-up. RESULTS: 375 patients were contacted and 153 failed to respond. The median timing for the follow-up assessment was 122 days (IQR, 109-158). On multivariate analyses, female gender, pre-existing lung disease, headache at presentation, intensive care unit (ICU) admission, critical COVID-19 and post-discharge ER visit were predictors of higher MRC scores at follow-up. Female gender, older age >67 years, arterial hypertension and emergency room (ER) visit were associated with lower MET exercise tolerance scores. Female gender, pre-existing lung disease, and ER visit were associated with higher risk of CFS. Age, dyslipidemia, hypertension, pre-existing lung disease and duration of symptoms were negatively associated with WHO-5 score. CONCLUSIONS: Several risk factors were associated with an increased risk of PACS. Hospitalized patients with COVID-19 who are at risk for PACS may benefit from a targeted pre-emptive follow-up and rehabilitation programs.

Early administration of remdesivir to COVID-19 patients associates with higher recovery rate and lower need for ICU admission: A retrospective cohort study.

OBJECTIVES: Remdesivir is one of the most widely recommended and used medications for COVID-19 treatment. However, different outcomes have been reported for hospitalized patients with COVID-19 treated with remdesivir. Specifically, the effect of the timing of remdesivir initiation (from patient's symptom onset) on clinical outcomes in COVID-19 patients has not been investigated. METHODS: This is a retrospective cohort study of patients hospitalized with COVID-19 and treated with or without remdisivir. The primary outcome was patient's recovery rate, defined as clinical improvement and patient's discharge by day 14 of symptom onset. The secondary outcome was the need for intensive care unit (ICU) admission, mechanical ventilation, and mortality within 28 days of patient's symptom onset. RESULTS: Out of 323 hospitalized adults with COVID-19, 107 (33.1%) received no remdesivir during their hospital stay, 107 (33.1%) received remdesivir early within 7 days of the symptom onset, and 109 (33.7%) received it at 8 days or later of symptom onset. At day 14 following symptom onset, higher proportion of patients recovered in the early remdesivir compared to the late remdesivir cohort, or patients who did not receive remdesivir (adjusted odds ratio, aOR, 2.65; 95% confidence interval [CI], 1.31 to 5.35). Moreover, early administration of remdesivir was associated with lower admission to intensive care unit (adjusted hazard ratio [aHR], 0.31; 95% CI, 0.15 to 0.64), less need for mechanical ventilation (aHR, 0.22; 95% CI, 0.10 to 0.51), and lower mortality at 28 days (aHR, 0.15; 95% CI, 0.04 to 0.53), as compared to the late remdesivir cohort or patients who did not receive remdesivir. CONCLUSION: Early administration of remdesivir within 7 days of symptom onset is associated with less need for mechanical ventilation and lower 28-days mortality.

Adenovirus and RNA-based COVID-19 vaccines' perceptions and acceptance among healthcare workers in Saudi Arabia: a national survey.

OBJECTIVES: The aim of this study was to compare the perception, confidence, hesitancy and acceptance rate of various COVID-19 vaccine types among healthcare workers (HCWs) in Saudi Arabia, a nation with Middle East respiratory syndrome coronavirus experience. DESIGN: National cross-sectional, pilot-validated questionnaire. SETTING: Online, self-administered questionnaire among HCWs. PARTICIPANTS: A total of 2007 HCWs working in the Kingdom of Saudi Arabia participated; 1512 (75.3%) participants completed the survey and were included in the analysis. INTERVENTION: Data were collected through an online survey sent to HCWs during 1-15 November 2020. The main outcome measure was HCW acceptance of COVID-19 candidate vaccines. The associated factors of vaccination acceptance were identified through a logistic regression analysis and via measurement of the level of anxiety, using the Generalised Anxiety Disorder 7 scale. RESULTS: Among the 1512 HCWs who were included, 62.4% were women, 70.3% were between 21 and 40 years of age, and the majority (62.2%) were from tertiary hospitals. In addition, 59.5% reported knowing about at least one vaccine; 24.4% of the participants were sure about their willingness to receive the ChAdOx1 nCoV-19 vaccine, and 20.9% were willing to receive the RNA BNT162b2 vaccine. However, 18.3% reported that they would refuse to receive the Ad5-vectored vaccine, and 17.9% would refuse the Gam-COVID-Vac vaccine. Factors that influenced the differential readiness of HCWs included their perceptions of the vaccine's efficiency in preventing the infection (33%), their personal preferences (29%) and the vaccine's manufacturing country (28.6%). CONCLUSIONS: Awareness by HCWs of the several COVID-19 candidate vaccines could improve their perceptions and acceptance of vaccination. Reliable sources on vaccine efficiency could improve vaccine uptake, so healthcare authorities should use reliable information to decrease vaccine hesitancy among frontline healthcare providers.

The psychological impact of the COVID-19 pandemic on adults and children in the United Arab Emirates: a nationwide cross-sectional study.

BACKGROUND: The psychosocial impact of previous infectious disease outbreaks in adults has been well documented, however, there is limited information on the mental health impact of the COVID-19 pandemic on adults and children in the United Arab Emirate (UAE) community. The aim of this study was to explore anxiety levels among adults and children in the UAE and to identify potential risk and protective factors for well-being during the COVID-19 pandemic. METHODS: Using a web-based cross-sectional survey we collected data from 2200 self-selected, assessed volunteers and their children. Demographic information, knowledge and beliefs about COVID-19, generalized anxiety disorder (GAD) using the (GAD-7) scale, emotional problems in children using the strengths and difficulties questionnaire (SDQ), worry and fear about COVID-19, coping mechanisms and general health information were collected. Descriptive analysis was carried out to summarize demographic and participant characteristics, Chi-square analysis to explore associations between categorical variables and anxiety levels and multivariable binary logistic regression analysis to determine predictors of anxiety levels in adults and emotional problems in children. RESULTS: The overall prevalence of GAD in the general population was 71% with younger people (59.8%) and females (51.7%) reporting highest levels of anxiety. Parents who were teachers reported the highest percentage of emotional problems in children (26.7%). Adjusted multivariable logistic regression for GAD-7 scores showed that being female, high levels of worry associated with COVID-19, intention to take the COVID-19 vaccine and smoking were associated with higher levels of anxiety. Adjusted multivariable logistic regression for SDQ showed that higher emotional problems were reported for children in lower and higher secondary education, and parents who had severe anxiety were seven times more likely to report emotional problems in their children. CONCLUSIONS: This study reports the psychological impact of COVID-19 among adults and children in the UAE and highlights the significant association between parental and child anxiety. Findings suggest the urgency for policy makers to develop effective screening and coping strategies for parents and especially children.

Disease phenotype and diagnostic delay in Saudi patients with primary Sjögren's syndrome: An exploratory cross-sectional study.

OBJECTIVES: To describe primary Sjögren's syndrome (pSS) cohort in Saudi Arabiain view in of clinical/serological/histopathological phentotype, and, diagnostic delay. METHODS: A cross-sectional study conducted between October 2018 and May 2019. Diagnostic delay was calculated from symptoms onset to clinical diagnosis. The European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) were calculated. RESULTS: Forty-one patients were included in the study. There were predominantly females (78%) with a mean (±SD) age of 58.76±12.7 and disease duration of 4.6±2.28 years. The mean diagnostic delay was 2.2±2.4 (range 1-11) years. Minor salivary gland biopsy was performed on 38 (92.7%) patients with a mean focus score of 2.3± 1.2 points. Interstitial lung disease and arthritis were the most common extra-glandular manifestations (EGM) affecting 27 (65.9%) patients for both. The mean ESSDAI was 9.95±7.73 and ESSPRI was 5.17±2.4. CONCLUSION: Saudi primary Sjogren's syndrome patients have a high prevalence of EGM predominantly arthritis and ILD. The diagnostic delay is variable in our cohort.

Sustained and targeted delivery of checkpoint inhibitors by metal-organic frameworks for cancer immunotherapy.

The major impediments to the implementation of cancer immunotherapies are the sustained immune effect and the targeted delivery of these therapeutics, as they have life-threatening adverse effects. In this work, biomimetic metal-organic frameworks [zeolitic imidazolate frameworks (ZIFs)] are used for the controlled delivery of nivolumab (NV), a monoclonal antibody checkpoint inhibitor that was U.S. Food and Drug Administration-approved back in 2014. The sustained release behavior of NV-ZIF has shown a higher efficacy than the naked NV to activate T cells in hematological malignancies. The system was further modified by coating NV-ZIF with cancer cell membrane to enable tumor-specific targeted delivery while treating solid tumors. We envisage that such a biocompatible and biodegradable immunotherapeutic delivery system may promote the development and the translation of hybrid superstructures into smart and personalized delivery platforms.