Effectiveness of Sinopharm's BBIBP-CorV Booster Vaccination against COVID-19-Related Severe and Critical Cases and Deaths in Morocco during the Omicron Wave.

OBJECTIVE: This study investigates the effectiveness of the 1st booster dose against COVID-19 severe and critical hospitalizations and deaths occurring due to the Omicron wave in Morocco. PARTICIPANTS/METHODS: This study uses nationally representative data on COVID-19 from 15 December 2021 to 31 January 2022. The aim is to investigate the effectiveness of the inactivated COVID-19 vaccine BBIBP-CorV (Sinopharm) 1st booster dose against the Omicron wave in Morocco using real-world data established from nationally representative statistics on COVID-19 cases, deaths and vaccinations. STATISTICAL ANALYSES: The screening method was used to estimate vaccine effectiveness against COVID-19 severe or critical hospitalization and COVID-19-related deaths. The data were grouped by, age subgroup, sex, week, and geographical area and were analyzed using binary logistic regression with an offset for vaccine coverage. RESULTS: The overall BBIBP-CorV VE estimate is 89% (95% CI 85 to 92) effective in curbing COVID-19 deaths, and 81% (95% CI 78 to 84 in curbing COVID-19 severe/critical hospitalizations. Death-related VE estimate was 86% (95% CI 81 to 90) for patients aged ≥65 years, 96% (95% CI 90 to 98) for those aged <65 years, 95% (95% CI 88 to 98) in no-risk factor patients, 91% (95% CI 85 to 94) with 1 risk factor, 90% (95% CI 83 to 95) with 2 risk factors, and 72% (95% CI 52 to 84) in patients with 3 risk factors and more. Severe/critical hospitalization VE estimate was 78% (95% CI 74 to 82) for patients aged ≥65 years, 87% (95% CI 82 to 90) for those aged <65 years, 86% (95% CI 80 to 90) in no-risk factor patients, 80% (95% CI 73 to 84) with 1 risk factor, 80% (95% CI 70 to 85) with 2 risk factors, and 80% (95% CI 68 to 86) in patients with 3 risk factors and more. CONCLUSIONS: BBIBP-CorV boosters are effective in increasing protection against the Omicron variant-related COVID-19 deaths and severe/critical hospitalizations. The protection is reduced with older age and higher risk factors. These findings emphasize the importance of targeted vaccination strategies for different demographic groups and underscore the protective benefits of the first booster BBIBP-CorV vaccine.

Genome sequencing of severe acute respiratory syndrome COVID-19 EF.1 variant strain obtained from a Moroccan patient.

Here, we report the identification and coding-complete genome sequence of a severe acute respiratory syndrome COVID-19 (SARS-CoV-2) strain obtained from a Moroccan patient. The detected strain EF.1 belongs to the BQ1.1 subvariant of the BA.5 Omicron variant.

Psychological Distress Associated with Enforced Hospital Isolation Due to COVID-19 during the "Flatten the Curve" Phase in Morocco: A Single-Center Cross-Sectional Study.

(1) Background: although much research has highlighted the mental health challenges faced by patients in hospital isolation during the COVID-19 pandemic, data from low-middle-income countries, including Morocco, are lacking. The main objective of this study was to assess the psychological distress of patients undergoing enforced hospital isolation during the initial phase of the COVID-19 pandemic in Morocco. (2) Methods: we conducted a cross-sectional study between 1 April and 1 May 2020, among patients hospitalized in isolation for suspected or confirmed COVID-19 at the Ibn Sina University Hospital of Rabat, Morocco. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Binary logistic regression was performed to identify variables associated with anxiety and depression, with a cutoff of ≥8 used for both scales to create dichotomous variables. (3) Results: among 200 patients, 42.5% and 43% scored above the cut-off points for anxiety and depression, respectively. Multiple logistic regression identified female gender, a higher education level, a longer duration of isolation, and a poor understanding of the reasons for isolation as significant factors associated with anxiety. Conversely, female gender, chronic disease, a longer duration of isolation, and a poor understanding of the reasons for isolation were factors significantly associated with depression. (4) Conclusions: our study underscores high rates of anxiety and depression among patients forced into hospital isolation during the initial phase of COVID-19 in Morocco. We identified several factors associated with patients experiencing psychological distress that may inform future discussions on mental health and psychiatric crisis management.

Exploring the hemicellulolytic properties and safety of Bacillus paralicheniformis as stepping stone in the use of new fibrolytic beneficial microbes.

Bacillus strains from the Moroccan Coordinated Collections of Microorganisms (CCMM) were characterised and tested for fibrolytic function and safety properties that would be beneficial for maintaining intestinal homeostasis, and recommend beneficial microbes in the field of health promotion research. Forty strains were investigated for their fibrolytic activities towards complex purified polysaccharides and natural fibres representative of dietary fibres (DFs) entering the colon for digestion. We demonstrated hemicellulolytic activities for nine strains of Bacillus aerius, re-identified as Bacillus paralicheniformis and Bacillus licheniformis, using xylan, xyloglucan or lichenan as purified polysaccharides, and orange, apple and carrot natural fibres, with strain- and substrate-dependent production of glycoside hydrolases (GHs). Our combined methods, based on enzymatic assays, secretome, and genome analyses, highlighted the hemicellulolytic activities of B. paralicheniformis and the secretion of specific glycoside hydrolases, in particular xylanases, compared to B. licheniformis. Genomic features of these strains revealed a complete set of GH genes dedicated to the degradation of various polysaccharides from DFs, including cellulose, hemicellulose and pectin, which may confer on the strains the ability to digest a variety of DFs. Preliminary experiments on the safety and immunomodulatory properties of B. paralicheniformis fibrolytic strains were evaluated in light of applications as beneficial microbes' candidates for health improvement. B. paralicheniformis CCMM B969 was therefore proposed as a new fibrolytic beneficial microbe candidate.

Draft genome sequence of a mosquito repellent Bacillus licheniformis strain Ba1 isolated from desert soil.

Microbial volatile organic compounds have been shown to affect a wide insect behavior. In this paper, we report the draft genome sequence of Bacillus licheniformis strain Ba1 previously isolated from desert soil in Morocco. The assembled and annotated draft genome contains 4,726 coding genes, 6 rRNAs and 97 tRNAs.

Genetic characterization of Schuurs-Hoeijmakers syndrome in a moroccan individual with heterozygote PACS1 mutation.

BACKGROUND: Schuurs-Hoeijmakers syndrome, an autosomal dominant neurodevelopmental genetic disorder, is a rare cause of intellectual disability (ID) affecting approximately 1 to 3% of all over the world. Only 87 cases have been recorded to date, and oddly enough, the majority of them share the same mutation (c.607 C > T; p.R203W). CASE PRESENTATION: This study presents the first reported case in Morocco of a 12-year-old female patient with PACS1 syndrome, identified during a cohort study of 24 patients with intellectual disability. The syndrome is caused by a de novo mutation of the PACS1 gene, located on chromosome 11, resulting in a single amino acid modification on the PACS1 protein. The abnormal protein disrupts cellular transport processes, leading to intellectual developmental delay, facial dysmorphia, and congenital anomalies. METHODS AND RESULTS: Exome sequencing was employed to identify the genetic mutation, and Sanger sequencing validated the presence of the recurrent mutation c.607 C > T (p.Arg203Trp) in the PACS1 gene. The mutation was found to be heterozygous and de novo, suggesting that it was not inherited from the patient's parents. Classification based on the American College of Medical Genetics and Genomics (ACMG) criteria confirmed its pathogenicity, with supporting evidence from bioinformatics analysis. The rarity of this variant in population databases further supports its pathogenic nature. CONCLUSION: This study expands our understanding of Schuurs-Hoeijmakers syndrome, a disorder with limited reported cases globally. The genetic heterogeneity of the disorder is highlighted, with the recurrent mutation being the most common pathogenic variant. Functional studies indicate the crucial role of PACS1 in craniofacial development and neurodevelopmental processes, with potential implications for autism spectrum disorders (ASD). Comprehensive genetic analyses are essential for accurate diagnosis and understanding the underlying causes of intellectual disabilities. Further research is warranted to unravel the mechanisms and potential therapeutic targets associated with PACS1-related neurodevelopmental disorders.

Circulating microRNA profiles in Wilms tumour (WT): A systematic review and meta-analysis of diagnostic test accuracy.

Background: Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods: Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results: Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions: Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number: CRD42022301597.

Coding-Complete Genome Sequences of an Omicron Subvariant (BA.5.2.20) of SARS-CoV-2.

Here, we present the complete coding sequences of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains that were recovered from a nasopharyngeal swab from a female patient and the second viral passage in cell culture. After testing, both strains were identified as BA.5.2.20, a subvariant of Omicron.

SARS-CoV-2-Neutralizing Antibody Response and Correlation of Two Serological Assays with Microneutralization.

SARS-CoV-2 has caused a huge pandemic affecting millions of people and resulting innumerous deaths. A better understanding of the correlation between binding antibodies and neutralizing antibodies is necessary to address protective immunity post-infection or vaccination. Here, we investigate the humoral immune response and the seroprevalence of neutralizing antibodies following vaccination with adenovirus-based vector in 177 serum samples. A Microneutralization (MN) assay was used as a reference method to assess whether neutralizing antibody titers correlated with a positive signal in two commercially available serological tests:a rapid lateral flow immune-chromatographic assay (LFIA) and an enzyme-linked Fluorescence Assay (ELFA). Neutralizing antibodies were detected in most serum samples (84%). COVID-19 convalescent individuals showed high antibody titers and significant neutralizing activity. Spearman correlation coefficients between the serological and neutralization results ranged from 0.8 to 0.9, suggesting a moderate to strong correlation between commercial immunoassays test results (LFIA and ELFA) and virus neutralization.

Improvement of the Chemical Reactivity of Michael Acceptor of Ethacrynic Acid Correlates with Antiproliferative Activities.

The present study aims to report the design, synthesis, and biological activity of new ethacrynic acid (EA) analogs (6-10) obtained by the double modulation of the carboxylic acid moiety and the aromatic ring with the aim to increase the chemical reactivity of Michael acceptor of EA. All obtained compounds were characterized by 1H and 13C NMR, IR, and high-resolution mass spectrometry. The antiproliferative activity was evaluated in vitro using MMT test, in a first step, against HL60 cell line and in a second step, on a panel of human cancer cell lines such as HCT116, A549, MCF7, PC3, U87-MG, and SKOV3, and normal cell line MRC5 in comparison with positive control doxorubicin. Among all the tested compounds, the product 8 containing a propargyl and a hydroxyl groups, allowing an intramolecular hydrogen bond with the keto group of EA, exhibited a pronounced and selective activity in a nanomolar range against HL60, A549, PC3, and MCF7 with IC50 values of 15, 41.2, 68.7, and 61.5 nM, respectively. Compound 8 also showed a good selectivity index (SI) against HL60 and moderate SI against the other three human cancer cells (A549, PC3, and MCF7). The study of the structure-activity relationship showed that both modifications of the carboxylic group and the introduction of an intramolecular hydrogen bond are highly required to improve the antiproliferative activities. The molecular modeling studies of compound 8 revealed that it favorably binds to the glutathione S-transferase active site, which may explain its interesting anticancer activity. These new compounds have potential to be developed as novel therapeutic agents against various cancer types.

Coding-Complete Sequence of a SARS-CoV-2 Strain from an Omicron (B.1.1.529+BA.1) Variant Detected in Morocco.

Here, we describe the coding-complete sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain HM36, identified as a strain of concern of B.1.1.529+BA (Omicron).

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin ß2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child's parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.

Coding-Complete Genome Sequences of a Delta Subvariant (AY.33) of SARS-CoV-2 Obtained from Moroccan COVID-19 Patients.

We report here the complete genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from Moroccan patients with COVID-19. The analysis of these sequences indicates that the identified strains belong to the AY.33 sublineage of the Delta variant.

Computational screening of potential drugs against COVID-19 disease: the Neuropilin-1 receptor as molecular target.

The transmembrane receptor Neuropilin-1 (NRP-1) was reported to serve as a host cell entry factor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19 disease. Therefore, molecular compounds interfering with SARS-CoV-2 binding to NRP-1 seem to be potential candidates as new antiviral drugs. In this study, NRP-1 receptor was targeted using a library of 1167 compounds previously analyzed in COVID-19 related studies. The results show the effectiveness of Nafamostat, Y96, Selinexor, Ebastine and UGS, in binding to NRP-1 receptor, with docking scores lower than - 8.2 kcal/mol. These molecules interact with NRP-1 receptor key residues, which makes them promising drugs to pursue further biological assays to explore their potential use in the treatment of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00751-x.

Genome Sequences of the Delta Variant (B.1.617.2) and the Kappa Variant (B.1.617.1) Detected in Morocco.

Here, we report the identification and coding-complete genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains obtained from patients with COVID-19. The strains identified belong to variant of concern B.1.617.2 and variant of interest B.1.617.1.

Hemicellulosic biomass conversion by Moroccan hot spring Bacillus paralicheniformis CCMM B940 evidenced by glycoside hydrolase activities and whole genome sequencing.

Thermophilic bacteria, especially from the genus Bacillus, constitute a huge potential source of novel enzymes that could be relevant for biotechnological applications. In this work, we described the cellulose and hemicellulose-related enzymatic activities of the hot spring Bacillus aerius CCMM B940 from the Moroccan Coordinated Collections of Microorganisms (CCMM), and revealed its potential for hemicellulosic biomass utilization. Indeed, B940 was able to degrade complex polysaccharides such as xylan and lichenan and exhibited activity towards carboxymethylcellulose. The strain was also able to grow on agriculture waste such as orange and apple peels as the sole carbon source. Whole-genome sequencing allowed the reclassification of CCMM B940 previously known as B. aerius into Bacillus paralicheniformis since the former species name has been rejected. The draft genome reported here is composed of 38 contigs resulting in a genome of 4,315,004 bp and an average G + C content of 45.87%, and is an important resource for illuminating the molecular mechanisms of carbohydrate metabolism. The annotated genomic sequences evidenced more than 52 genes encoding glycoside hydrolases and pectate lyases belonging to 27 different families of CAZymes that are involved in the degradation of plant cell wall carbohydrates. Genomic predictions in addition to in vitro experiments have revealed broad hydrolytic capabilities of the strain, thus reinforcing its relevance for biotechnology applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02919-0.

Identification of the novel SDR42E1 gene that affects steroid biosynthesis associated with the oculocutaneous genital syndrome.

Hereditary connective tissue diseases form a heterogeneous group of disorders that affect collagen and extracellular matrix components. The cornea and the skin are among the major forms of connective tissues, and syndromes affecting both organs are often due to mutations in single genes. Brittle cornea syndrome is one of the pathologies that illustrates this association well. Furthermore, sex hormones are known to play a role in the maintenance of the structure and the integrity of the connective tissue including the skin and cornea, and may be involved in pathogenesis of oculocutaneous diseases. Herein, a double consanguineous family of Moroccan origin with two affected siblings, with suspected brittle cornea syndrome, was recruited. Ophthalmic examinations and genetic testing were performed in all the nuclear family individuals. Clinical examinations showed that the two affected boys presented with thinning of the cornea, blue sclera, keratoconus, hyperelasticity of the skin, joint hypermobility, muscle weakness, hearing loss and dental abnormalities that are compatible with the diagnosis of BCS disease. They showed however additional clinical signs including micropenis, hypospadias and cryptorchidism, suggesting abnormalities in endocrine pathways. Using a duo exome sequencing analysis performed in the mother and the propositus, we identified the novel homozygous missense mutation c.461G > A (p.Arg154Gln) in the short-chain dehydrogenase/reductase family 42E member 1 (SDR42E1) gene. This novel mutation, which co-segregated with the disease in the family, was predicted to be pathogenic by bioinformatics tools. SDR42E1 stability analysis using DynaMut web-server showed that the p.Arg154Gln mutations has a destabilizing effect with a ΔΔG value of -1.039 kcal/mol. As this novel gene belongs to the large family of short-chain dehydrogenases/reductases (SDR) thought to be involved in steroid biosynthesis, endocrinological investigations subsequently revealed that the two patients also had low levels of cholesterol. Karyotyping revealed a normal 46,XY karyotype for the two boys, excluding other causes of disorders of sex development due to chromosomal rearrangements. In conclusion, our study reveals that mutation in the novel SDR42E1 gene alters the steroid hormone synthesis and associated with a new syndrome we named oculocutaneous genital syndrome. In addition, this study highlights the role of SDR42E1 in the regulation of cholesterol metabolism in the maintenance of connective tissue and sexual maturation in humans.

Complete Genome Sequence of a SARS-CoV-2 Strain Sampled in Morocco in May 2020, Obtained Using Sanger Sequencing.

The complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain was obtained. The strain was isolated from a nasopharyngeal swab specimen from a female patient in Rabat, Morocco, with coronavirus disease 2019 (COVID-19). This strain belongs to clade 20A and has 12 mutations and 8 amino acid substitutions compared to the reference strain Wuhan/Hu-1/2019.

Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco.

BACKGROUND: To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. METHODS: Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. RESULTS: Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. CONCLUSION: Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

Evidence for zoonotic transmission of species A rotavirus from goat and cattle in nomadic herds in Morocco, 2012-2014.

Species A rotaviruses (RVAs) are a leading cause of diarrhea in children and in the young of a large variety of mammalian and avian host species. The purpose of this study was to identify RVA in nomadic goats and calves during severe diarrhea outbreaks in 2012 and 2014 in Bouaarfa, Morocco, and to characterize the complete genomic constellation of two bovine and caprine strains (S18 and S19) and their genetic relatedness with the human strain ma31 detected in 2011 in Morocco. Partial nucleotide sequencing of VP4 and VP7 genes for the twenty-two positive samples revealed three circulating genotypes: G6P[14], G10P[14], and G10P[5] with predominance of G6P[14] genotype. Full-genome sequencing for both strains S18 and S19 presented, respectively, the following genomic constellations: G6-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3 and G10-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3. Phylogenetic analyses and the analysis of the VP8* antigenic epitopes for S18, S19 and ma31 revealed a shared similarity with bovine, caprine, ovine and human strains from Morocco and other countries. The VP2 and NSP1 genes of the S19 strain were closely related to those of the cognate genes of the human ma31 strain, while the VP4 gene of S18 strain was closely related to the cogent gene of the ma31 strain. Our findings revealed cases of zoonotic transmission and confirmed the risk of emergence of new genotypes in some environments such as nomadic regions, where close physical proximity between human and livestock is common. The present study is novel in reporting whole-genome analyses of RVA isolates obtained from nomadic livestock in Morocco.