Assessing the impact of COVID-19 on acute leukemia patients: a comparative analysis of hematological and biochemical parameters.

BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia. METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained. RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2. CONCLUSION: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.

Nanopore ReCappable sequencing maps SARS-CoV-2 5' capping sites and provides new insights into the structure of sgRNAs.

The SARS-CoV-2 virus has a complex transcriptome characterised by multiple, nested subgenomic RNAsused to express structural and accessory proteins. Long-read sequencing technologies such as nanopore direct RNA sequencing can recover full-length transcripts, greatly simplifying the assembly of structurally complex RNAs. However, these techniques do not detect the 5' cap, thus preventing reliable identification and quantification of full-length, coding transcript models. Here we used Nanopore ReCappable Sequencing (NRCeq), a new technique that can identify capped full-length RNAs, to assemble a complete annotation of SARS-CoV-2 sgRNAs and annotate the location of capping sites across the viral genome. We obtained robust estimates of sgRNA expression across cell lines and viral isolates and identified novel canonical and non-canonical sgRNAs, including one that uses a previously un-annotated leader-to-body junction site. The data generated in this work constitute a useful resource for the scientific community and provide important insights into the mechanisms that regulate the transcription of SARS-CoV-2 sgRNAs.

Prevalence and association of hyperuricemia with liver function in Saudi Arabia: a large cross-sectional study.

BACKGROUND: Hyperuricemia is linked to an increased risk of various chronic diseases, but data on the prevalence and association of hyperuricemia with liver function in Saudi Arabia are scarce. OBJECTIVES: Evaluate the prevalence, association, and risk measures of hyperuricemia and liver function in the Saudi population. DESIGN: Retrospective, cross-sectional analysis. SETTING: Database on large portion of Saudi population. PATIENTS AND METHODS: Laboratory data, age, and gender of the studied subjects were collected from Al Borg Diagnostics. Subjects were stratified, based on their uric acid (UA) levels, into three groups: hypouricemic, normouricemic, and hyperuricemic. The association of UA with liver enzymes was examined in all three groups. MAIN OUTCOME MEASURES: Association of serum UA levels with alanine transaminase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). SAMPLE SIZE: 13 314 subjects. RESULTS: Our study showed that the prevalence of hyperuricemia in the Saudi population is 17.3% (20.3% in males and 15.1% in females). We also found a positive correlation between ALT, AST, and TB with UA levels. The risk of being hyperuricemic was significantly increased in individuals with elevated ALT, AST, and TB. Individuals with elevated ALT, AST, and total TB had a higher chance of having hyperuricemia than those with normal activity. Notably, ALT, AST, and TB had good discriminating capacity for hyperuricemia. CONCLUSIONS: Hyperuricemia is highly prevalent in the Saudi population and is associated with compromised liver function. However, further studies are needed to elucidate the mechanisms underlying these findings in large prospective cohort studies in different populations. LIMITATIONS: Lack of data on other potential confounding variables.

Chemical Composition, Antioxidant, Anticancer, and Antibacterial Activities of Roots and Seeds of Ammi visnaga L. Methanol Extract.

For centuries, plants and their components have been harnessed for therapeutic purposes, with Ammi visnaga L. (Khella) being no exception to this rich tradition. While existing studies have shed light on the cytotoxic and antimicrobial properties of seed extracts, there remains a noticeable gap in research about the antimicrobial, antioxidant, and anticancer potential of root extracts. This study seeks to address this gap by systematically examining methanol extracts derived from the roots of A. visnaga L. and comparing their effects with those of seed extracts specifically against breast cancer cells. Notably, absent from previous investigations, this study focuses on the comparative analysis of the antimicrobial, antioxidant, and anticancer activities of both root and seed extracts. The methanol extract obtained from A. visnaga L. seeds demonstrated a notably higher level of total phenolic content (TPC) than its root counterpart, measuring 366.57 ± 2.86 and 270.78 ± 2.86 mg GAE/g dry weight of the dry extract, respectively. In the evaluation of antioxidant activities using the DPPH method, the IC50 values for root and seed extracts were determined to be 193.46 ± 17.13 µg/mL and 227.19 ± 1.48 µg/mL, respectively. Turning our attention to cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231), both root and seed extracts displayed similar cytotoxic activities, with IC50 values of 92.45 ± 2.14 µg/mL and 75.43 ± 2.32 µg/mL, respectively. Furthermore, both root and seed extracts exhibited a noteworthy modulation of gene expression, upregulating the expression of caspase and Bax mRNA levels while concurrently suppressing the expression of anti-apoptotic genes (Bcl-xL and Bcl-2), thereby reinforcing their potential as anticancer agents. A. visnaga L. seed extract outperforms the root extract in antimicrobial activities, exhibiting lower minimum inhibitory concentrations (MICs) of 3.81 ± 0.24 to 125 ± 7.63 µg/mL. This highlights the seeds' potential as potent antibacterial agents, expanding their role in disease prevention. Overall, this study underscores the diverse therapeutic potentials of A. visnaga L. roots and seeds, contributing to the understanding of plant-derived extracts in mitigating disease risks.

Assessing the Impact of COVID-19 Vaccines on Sickle Cell Anaemia Patients: A Comparative Analysis of Biochemical and Haematological Parameters.

The coronavirus disease 2019 (COVID-19) vaccines have been developed to help prevent the spread of the virus infections. The COVID-19 vaccines, including Pfizer, Moderna, and AstraZeneca, have undergone rigorous testing and have demonstrated both safety and effectiveness. Extensive evidence supports their effectiveness in preventing severe illness, hospitalization, and mortality associated with COVID-19 infection. The administration of COVID-19 vaccines can directly affect hematological and biochemical parameters, with reported cases showing an association with thrombosis and thrombocytopenia. Therefore, it was hypothesized that COVID-19 vaccines may also influence hematological and biochemical markers in sickle cell patients. This study aimed to investigate the side effects of COVID-19 vaccines on sickle cell patients, providing a comprehensive evaluation of hematological and biochemical parameters. To our knowledge, this is the first study of its kind conducted in Saudi Arabia. The study included the evaluation of Pfizer and Oxford-AstraZeneca vaccines in sickle cell patients, measuring key parameters. Our findings revealed varying impacts of both vaccines on the ALT, AST, and CRP levels. Notably, CRP and ALT exhibited potential as indicators for renal disease, diabetes, and arthritis. However, further investigations are necessary to uncover the underlying mechanisms that drive these observed differences and comprehend their clinical implications for this vulnerable patient population. The unique nature of our study fills a crucial research gap and underscores the need for additional research in this area.

Risk Factors for Glucose 6-Phosphate Dehydrogenase and COVID-19 Disease-A Retrospective Study at a Major Saudi Tertiary Center.

Glucose-6-phosphate dehydrogenase (G6PD) insufficiency is a common enzymatic defect worldwide; it affects over 400 million people and is associated with various disorders. Recent research suggests that G6PD-deficient cells are susceptible to infection by human coronaviruses, as the G6PD enzyme is involved in the metabolism of oxidative stress, which may enhance COVID-19 mortality. This retrospective study aimed to examine the effect of COVID-19 on patients with G6PD deficiency by comparing the laboratory parameters of patients with G6PD enzyme deficiency alone, COVID-19 alone, and those with both COVID-19 and G6PD enzyme deficiency treated at a major Saudi tertiary center. The results indicated significant differences in hematological and biochemical parameters between the three patient groups, indicating that COVID-19 may influence these parameters, and that they could be used to measure the severity of COVID-19 disease. Moreover, this study suggests that patients with G6PD enzyme deficiency may be at higher risk for severe COVID-19 outcomes. Although the study is limited by the lack of a random selection method for group membership, the Kruskal-Wallis H-test was used to statistical assess the data. The study's findings can enhance the understanding of the relation between COVID-19 infected and G6PD-deficiency patients and inform clinical decision making for an improved patient outcome.

Paediatric COVID-19 Outcomes: Haematology Parameters, Mortality Rates, and Hospitalization Duration.

The global COVID-19 pandemic has strained healthcare systems around the globe, necessitating extensive research into the variables that affect patient outcomes. This study examines the relationships between key haematology parameters, duration of hospital stay (LOS), and mortality rates in COVID-19 cases in paediatric patients. Researchers analyse relationships between independent variables (COVID-19 status, age, sex) and dependent variables (mortality, LOS, coagulation parameters, WBC count, RBC parameters) using multivariate regression models. Although the R-square values (0.6-3.7%) indicate limited explanatory power, coefficients with statistical significance establish the impact of independent variables on outcomes. Age emerges as a crucial predictor of mortality; the mortality rate decreases by 1.768% per age group. Both COVID-19 status and age have an inverse relationship with length of stay, emphasising the milder hospitalisation of children. Platelet counts decline with age and male gender, potentially revealing the influence of COVID-19 on haematological markers. There are significant correlations between COVID-19 status, age, gender and coagulation measures. Lower prothrombin time and D-dimer concentrations in elder COVID-19 patients are indicative of distinct coagulation profiles. WBC and RBC parameters exhibit correlations with variables: COVID-19-positive patients have lower WBC counts, whereas male COVID-19-positive patients have higher RBC counts. In addition, correlations exist between independent variables and the red cell distribution width, mean corpuscular volume, and mean corpuscular haemoglobin. However, there is no correlation between mean corpuscular haemoglobin concentration and outcomes, indicating complex interactions between haematological markers and outcomes. In essence, this study underlines the importance of age in COVID-19 mortality, provides novel insights into platelet counts, and emphasises the complexity of the relationships between haematological parameters and disease outcomes.

Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.

SARS-CoV-2 vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals low levels of viral backbone gene transcription alongside very high levels of SARS-CoV-2 S glycoprotein gene transcription.

BACKGROUND: ChAdOx1 nCoV-19 is a recombinant adenovirus vaccine against SARS-CoV-2 that has passed phase III clinical trials and is now in use across the globe. Although replication-defective in normal cells, 28 kbp of adenovirus genes is delivered to the cell nucleus alongside the SARS-CoV-2 S glycoprotein gene. METHODS: We used direct RNA sequencing to analyse transcript expression from the ChAdOx1 nCoV-19 genome in human MRC-5 and A549 cell lines that are non-permissive for vector replication alongside the replication permissive cell line, HEK293. In addition, we used quantitative proteomics to study over time the proteome and phosphoproteome of A549 and MRC5 cells infected with the ChAdOx1 nCoV-19 vaccine. RESULTS: The expected SARS-CoV-2 S coding transcript dominated in all cell lines. We also detected rare S transcripts with aberrant splice patterns or polyadenylation site usage. Adenovirus vector transcripts were almost absent in MRC-5 cells, but in A549 cells, there was a broader repertoire of adenoviral gene expression at very low levels. Proteomically, in addition to S glycoprotein, we detected multiple adenovirus proteins in A549 cells compared to just one in MRC5 cells. CONCLUSIONS: Overall, the ChAdOx1 nCoV-19 vaccine's transcriptomic and proteomic repertoire in cell culture is as expected. The combined transcriptomic and proteomics approaches provide a detailed insight into the behaviour of this important class of vaccine using state-of-the-art techniques and illustrate the potential of this technique to inform future viral vaccine vector design.