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Lower levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the nasal epithelium of children may be related to a lower incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, compared to adults. However, no direct evidence is available to support this hypothesis. In this study, we compared the transcript levels of ACE2 and TMPRSS2 in nasopharyngeal swab samples (n = 234) from children and adult family members within SARS-CoV-2-exposed families and assessed the association with SARS-CoV-2 infection status. Transcript levels for ACE2, but not TMPRSS2, were higher in adults than in children (n = 129 adults and 105 children; P

Background Pooling of samples for SARS‐CoV‐2 testing in low‐prevalence settings has been used as an effective strategy to expand testing capacity and mitigate challenges with the shortage of supplies. We evaluated two automated molecular test systems for the detection of SARS‐CoV‐2 RNA in pooled specimens. Methods Pooled nasopharyngeal and saliva specimens were tested by Qiagen QIAstat‐Dx Respiratory SARS‐CoV‐2 Panel (QIAstat) or Cepheid Xpert Xpress SARS‐CoV‐2 (Xpert), and the results were compared to that of standard RT‐qPCR tests without pooling. Results In nasopharyngeal specimens, the sensitivity/specificity of the pool testing approach, with 5 and 10 specimens per pool, were 77%/100% (n = 105) and 74.1%/100% (n = 260) by QIAstat, and 97.1%/100% (n = 250) and 100%/99.5% (n = 200) by Xpert, respectively. Pool testing of saliva (10 specimens per pool; n = 150) by Xpert resulted in 87.5% sensitivity and 99.3% specificity compared to individual tests. Pool size of 5 or 10 specimens did not significantly affect the difference of RT‐qPCR cycle threshold (CT) from standard testing. RT‐qPCR CT values obtained with pool testing by both QIAstat and Xpert were positively correlated with that of individual testing (Pearson's correlation coefficient r = 0.85 to 0.99, p, Pooled sample testing for SARS‐CoV‐2 using Cepheid Xpert and Qiagen QIAstat tests was evaluated. Analytical sensitivity of Xpert for detection of SARS‐CoV‐2 is higher than QIAstat. Sensitivity and specificity of detection in pool of 10 NP swabs by Xpert are 100% and 99.5% and by QIAstat are 74.1% and 99.5%, respectively. Sensitivity and specificity of detection in pool of 10 saliva samples by Xpert are 87.5% and 99.3%, respectively.

There is accumulating evidence that the lower levels of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the nasal epithelium of children may be related to a lower incidence of COVID-19 compared to adults. However, no direct evidence is available to support this hypothesis. In this study, we compared the transcript levels of ACE2 and TMPRSS2 in nasopharyngeal swabs (n=207) from children and adult members within COVID-19-exposed families and assessed their association with SARS-CoV-2 infection status. The expression of both genes was higher in adults compared to the children (n=115 adults and 92 children, p

Pooling of samples for SARS-CoV-2 testing in low prevalence settings has been used as an effective strategy to expand testing capacity and mitigate challenges associated with the shortage of supplies. We evaluated two automated molecular test systems for detection of SARS-CoV-2 RNA in pooled specimens. Pooled nasopharyngeal and saliva specimens were tested by Qiagen QIAstat-Dx Respiratory SARS-CoV-2 Panel (QIAstat) or Cepheid Xpert Xpress SARS-CoV-2 (Xpert), and the results were compared to that of standard RT-qPCR tests without pooling. In nasopharyngeal specimens, the sensitivity/specificity of the pool-testing approach, with 5 and 10 specimens per pool, were 77%/100% (n=105) and 74.1%/100% (n=260) by QIAstat, and 97.1%/100% (n=250) and 100%/99.5% (n=200) by Xpert, respectively. Pool-testing of saliva (10 specimens per pool; n=150) by Xpert resulted in 87.5% sensitivity and 99.3% specificity compared to individual tests. Pool size of 5 or 10 specimens did not significantly affect the difference of RT-qPCR cycle threshold (CT) values from standard testing. RT-qPCR CT values obtained with pool testing by both QIAstat or Xpert were positively correlated with that of individual testing (Pearson correlation coefficient r=0.85 to 0.99, pT values from Xpert were significantly stronger (p

Background and aims Alzheimer disease (AD) is a progressive and complex neurodegenerative disease. Approximately 70% of AD risk is attributed to genetic risk factors, including variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Several studies have revealed a considerable number of candidate loci and genes for AD among different ethnic populations. However, the outcomes of these studies have been inconsistent. In this study, we aimed to investigate the spectrum of variants that are associated with the onset and development of AD among 22 Arab countries. Methodology We systematically searched 4 literature databases (Science Direct, Scopus, PubMed, and Web of Science) from the date of inception until July 2020 using various search terms to obtain all the reported genetic data on Arab AD cases. Results In total, 18 studies were included, comprising a total of 2173 individuals, of whom 888 were clinically diagnosed AD patients and were genetically tested for genes and variants associated with AD. A total of 27 variants in 8 genes were found to be associated with AD. Of these variants, 17 were unique to the Arab population and 10 were shared with other ethnic groups. Conclusions There is a dearth of studies on the genetics of AD in the Arab world. There seems to be distinctive genetic and clinical susceptibility profiles for Arab patients with AD.

Background: COVID-19 screening in healthcare facilities plays a key role in the management of the ongoing pandemic. Rapid and reliable detection of the virus ensures early identification of cases and targeted measures to prevent transmission of the virus. QIAstat-Dx Respiratory SARS-CoV-2 Panel (QRSP) is a fully automated rapid multiplex PCR assay for common respiratory pathogens including SARS-CoV-2 that can provide sample to result in 70 minutes. However, these tests are less suitable as screening tests because of their high cost and lower throughput. Objective: In this study, we evaluated the performance of QRSP on pooled nasopharyngeal specimens to reduce the cost and improve the turn-around time (TAT) for reporting negative COVID-19 results in a low prevalence setting. Methods: Nasopharyngeal (NP) specimens were simultaneously tested by pooled QRSP (~10 specimens/pool) approach and by standard RT-qPCR, and the results were compared. TAT of reporting negative results with pooled QRSP tests were compared to that of standard testing.Results: In 208 specimens, QRSP test results with specimen pooling were in 96% agreement (Kappa=0.92; 95%CI= 0.75-1) with standard RT-qPCR. Despite pooling, CT values obtained with QRSP were correlated with that of standard RT-qPCR (Pearson correlation coefficient r=0.8343, p=0.0027). The median TAT for negative COVID-19 results by QRSP pooled approach was 2.8 hours (n=1305) compared to 5.4 hours by standard methods (n=4471).Conclusion: Pooled QRSP testing can be implemented for COVID-19 screening in low prevalence settings providing significant cost savings and improving TAT without affecting test quality.

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1&ndash, 242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.