SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Efficacy of Repeated Low-Level Red Light (RLRL) therapy on myopia outcomes in children: a systematic review and meta-analysis.

BACKGROUND: Myopia is the most prevalent form of refractive error that has a major negative impact on visual function and causes blurring of vision. We aimed to determine if Repeated Low-Level Red Light (RLRL) treatment is beneficial in treating childhood myopia in terms of axial length (AL), spherical equivalent refraction (SER), and sub foveal choroidal thickness (SFCT). METHODS: This systematic review was performed on RLRL for treatment of myopia in children compared to single vision spectacles (SVS). We employed the search strategy with key terms myopia and low-level light therapy then we searched PubMed, Scopus, Cochrane, and Web of Science databases. The mean differences (MD) were used to evaluate the treatment effects. Heterogeneity was quantified using I2 statistics and explored by sensitivity analysis. RESULTS: Five randomized controlled trials (RCTs) were included in our meta-analysis with a total of 833 patients, 407 in treatment group and 426 in control group. At a 3 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.16; 95% CI [-0.19, -0.12], SER (MD = 0.33; 95% CI [0.27, 0.38]), and SFCT (MD = 43.65; 95% CI [23.72, 45.58]). At a 6 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.21; 95% CI [-0.28, -0.15]), SER (MD = 0.46; 95% CI [0.26, 0.65]), and SFCT (MD = 25.07; 95% CI [18.18, 31.95]). At a 12 month follow up period, pooled studies show a statistical difference in AL between RLRL and SVS group (MD = -0.31; 95% CI [-0.42, -0.19]) and SER (MD = 0.63; 95% CI [0.52, 0.73]). CONCLUSION: This is the first systematic review and meta-analysis investigating only RCTs evidence supporting the efficacy of 650 nm RLRL for myopia control in the short term of 3, 6, and 12 months follow up. The present review revealed the clinical significance of RLRL as a new alternative treatment for myopia control with good user acceptability and no documented functional or structural damage. However, the effect of long-term RLRL treatment and the rebound effect after cessation require further investigations.

Memory T Cells Discrepancies in COVID-19 Patients.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

Serological and genetic diversity of hepatitis E virus among rabbits population in Egypt.

Background: Hepatitis E virus (HEV) infection has a worldwide distribution and represents an important cause of acute hepatitis. Data on rabbit HEV prevalence and genetic diversity in hyperendemic regions (Egypt) are limited, per the information on rabbit HEV's implications for human pathology. Aim: This study aimed to determine the prevalence of HEV infection in farmed rabbits from hyperendemic (Egypt) regions, as well as to examine the genetic relatedness of rabbit strains to human strains isolated in these regions. Methods: Anti-HEV was tested by ELISA from 164 serum samples isolated from rabbits in Egypt. HEV RNA was tested using reverse transcription of a nested polymerase chain reaction with degenerative primers to open reading frames 2 in feces samples from 355 farmed rabbits from Egypt (3 farms from different regions). Results: All of the animals were between the ages of 2 and 24 months. Age groups at various governorates, with the bulk of infections occurring between the ages of 2 and 12 months. HEV RNA prevalence in rabbits at the age between 2 and 12 months was varied in different governorates from 13.40%, 18.20%, and 32.10% in Qena, Luxor, and Assiut, respectively. While at the age between 12 and 24 months, HEV RNA prevalence in rabbits was 0.0%, 3.70%, and 4.30% in Assiut, Qena, and Luxor, respectively. Phylogenetic analysis did not reveal any relatedness of rabbit HEV strains neither to HEV genotype 3 sequences from patients with autochthonous hepatitis E in Egypt. Conclusion: HEV is prevalent in rabbits from Egypt with other rabbit strains belonging to species-specific group which is close to genotype 3.

Human Wharton's Jelly Mesenchymal Stem Cells Secretome Inhibits Human SARS-CoV-2 and Avian Infectious Bronchitis Coronaviruses.

Human SARS-CoV-2 and avian infectious bronchitis virus (IBV) are highly contagious and deadly coronaviruses, causing devastating respiratory diseases in humans and chickens. The lack of effective therapeutics exacerbates the impact of outbreaks associated with SARS-CoV-2 and IBV infections. Thus, novel drugs or therapeutic agents are highly in demand for controlling viral transmission and disease progression. Mesenchymal stem cells (MSC) secreted factors (secretome) are safe and efficient alternatives to stem cells in MSC-based therapies. This study aimed to investigate the antiviral potentials of human Wharton's jelly MSC secretome (hWJ-MSC-S) against SARS-CoV-2 and IBV infections in vitro and in ovo. The half-maximal inhibitory concentrations (IC50), cytotoxic concentration (CC50), and selective index (SI) values of hWJ-MSC-S were determined using Vero-E6 cells. The virucidal, anti-adsorption, and anti-replication antiviral mechanisms of hWJ-MSC-S were evaluated. The hWJ-MSC-S significantly inhibited infection of SARS-CoV-2 and IBV, without affecting the viability of cells and embryos. Interestingly, hWJ-MSC-S reduced viral infection by >90%, in vitro. The IC50 and SI of hWJ-MSC secretome against SARS-CoV-2 were 166.6 and 235.29 µg/mL, respectively, while for IBV, IC50 and SI were 439.9 and 89.11 µg/mL, respectively. The virucidal and anti-replication antiviral effects of hWJ-MSC-S were very prominent compared to the anti-adsorption effect. In the in ovo model, hWJ-MSC-S reduced IBV titer by >99%. Liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis of hWJ-MSC-S revealed a significant enrichment of immunomodulatory and antiviral proteins. Collectively, our results not only uncovered the antiviral potency of hWJ-MSC-S against SARS-CoV-2 and IBV, but also described the mechanism by which hWJ-MSC-S inhibits viral infection. These findings indicate that hWJ-MSC-S could be utilized in future pre-clinical and clinical studies to develop effective therapeutic approaches against human COVID-19 and avian IB respiratory diseases.

Diagnostic value of soluble programmed cell death protein-1 in type-1 autoimmune hepatitis in Egyptian children.

Programmed cell death protein-1 (PDCD1) is considered a key factor in immune regulation and is expressed mainly on activated T cells. The current study aimed to assess the clinical value of soluble PDCD1/PD1 as a marker for diagnosing type-1 autoimmune hepatitis in children. Sixty children with chronic hepatitis as patients' groups further divided into autoimmune hepatitis group and other chronic liver disease group and 20 healthy children as a control group were enrolled in this study. All children have been studied for clinical profile, biochemical, histological features and serum level of soluble programmed cell death protein-1 by ELISA. There was a significant increase regarding soluble PDCD1/PD1 in the autoimmune hepatitis group than the chronic liver disease group, with the lowest level in the control group. Soluble PDCD1/PD1 level increased with higher fibrosis stage and higher Child Pugh score, also higher in relapsed patients than patients with complete remission in AIH groups. There was a positive correlation between soluble PDCD1/PD1 and PT, IgG, fibrosis stage, HAI, ALT, AST, simplified and revised score system, PELD and MELD among the AIH group. The best cutoff value of PDCD1/PD1 in the prediction of autoimmune hepatitis was 1.73 ng/ml with AUC:0.895 that has a sensitivity of 80%, specificity of 78%. sPDCD1/PD1 level represents a possible promising biomarker of AIH patients who will represent an incomplete response for regular treatment. This finding can be considered as the first step to prove the pivotal role of soluble PDCD1/PD1 in the diagnosis of AIH.

Timing of tracheostomy in patients with prolonged endotracheal intubation: a systematic review.

The objective of this article is to evaluate the appropriate timing of tracheostomy in patients with prolonged intubationregarding the incidence of hospital-acquired pneumonia, mortality, length of stay in intensive care unit (ICU) and duration of artificial ventilation. The study included published articles yielded by a search concerning timing of tracheostomy in adult and pediatric patients with prolonged intubation. The search was limited to articles published in English language in the last 30 years (between 1987 and 2017). For the 690 relevant articles, we applied our inclusion and exclusion criteria and only 43 articles were included. 41 studies in the adult age group including 222,501 patients and 2 studies in pediatric age group including 140 patients met our criteria. Studies in adult age group were divided into three groups according to the methodology of determining the cut off timing for early tracheostomy, they were divided into studies that considered early tracheostomy within the first 7, 14 or 21 days of endotracheal intubation, while in pediatric age group the cut off timing for early tracheostomy was within the first 7 days of endotracheal intubation. There was a significant difference in favor of early tracheostomy in adults' three groups and pediatric age group as early tracheostomy was superior regarding reduced duration of mechanical ventilation, with less mortality rates and less duration of stay in ICU. Regarding hospital-acquired pneumonia, it was significantly less in adult groups but with no significant difference in pediatric age group (3 patients out of 72 pediatric patient with early tracheostomy had pneumonia compared to 11 patients out of 68 with late tracheostomy). Studies defining early tracheostomy as that done within 7 days of intubation had better results than those defining early tracheostomy as that done within 14 or 21 days of intubation. In conclusion, early tracheostomy within 7 days of intubation should be done for both adults and pediatric patients with prolonged intubation.

Staphylococcal infection and toxin production in chronic rhinosinusitis.

BACKGROUND: The association between bacterial colonization and different forms of chronic rhinosinusitis (CRS) has not been well documented. One of the most recent hypotheses is superantigen (SA)-induced inflammation, resulting in up-regulation of lymphocytes to produce cytokines, and other inflammatory mediators that strongly modify the disease. Staphylococcus aureus, frequently encountered in nasal passages, can produce enterotoxins that can act as SAs. METHODS: A prospective case control study was performed. Sixty-four patients diagnosed with CRS (group 1), CRS with nasal polyps (CRSwNP) (group 2), and 15 control subjects were enrolled. Swabs were taken from the middle meatus of all subjects for identification of S. aureus carriers. Positive carriers were analyzed for the presence of toxic shock syndrome toxin (TSST) 1 using reverse passive latex agglutination as well as polymerase chain reaction. RESULTS: The rate of nasal carriage of S. aureus in CRS was 42.8%, that of CRSwNP was 45.4%, and that of the control group was 13.3%. The difference between both groups of CRS and the control group was found to be highly significant (p < 0.001). The detection of TSST-1 was significantly higher (p < 0.001) in both groups of CRS patients than in the control group. Finally, the difference in colonization of TSST-1 was highly significant (p < 0.001) between the CRS group 1 and CRSwNP group 2 patients. CONCLUSION: Identifying SAs and understanding how they elicit the pathogenic condition in CRS will be central in revealing ways to ameliorate their effects and properly treat these conditions.

Prognostic value of cell-cycle regulators and cellular biomarkers in laryngeal squamous cell carcinoma.

OBJECTIVE: Combining information derived from cellular biomarkers as telomerase and genes encoding cyclin dependent kinase inhibitors (p16(INK4a) and p15(INK4b)) is needed to facilitate the stratification of individual patients within the conventional clinicopathologic parameters. DESIGN AND METHODS: One hundred forty laryngeal squamous cell carcinoma (LSCC) tissue specimens were investigated for telomerase activity and the deletions of p16(INK4a) and p15(INK4b) genes. RESULTS: Of the 140 tissues assayed, 71% demonstrated high telomerase activity, 68.6% and 80% showed deletions in p16(INK4a) and p15(INK4b) genes, respectively. Significant difference was observed between telomerase activity, p16(INK4a) and p15(INK4b) deletions among each other and with advanced stage, poorly differentiated grades, high proliferation and DNA aneuploidy. The markers and the aforementioned clinicopathological factors were correlated with progression in univariate analysis; and associated with survival in multivariate analysis. CONCLUSION: Progression of LSCC is accompanied by a parallel increase in telomerase activity and deletions in cell-cycle regulators (p16(INK4a), p15(INK4b)) which may assist in prognostication and better classification of patients for treatment.