A sustainable approach for the degradation kinetics study and stability assay of the SARS-CoV-2 oral antiviral drug Molnupiravir.

Molnupiravir (MPV) is the first direct-acting oral antiviral drug that effectively decreases nasopharyngeal infections with SARS-CoV-2 virus. The stability of MPV was tested by subjecting the drug to various stress conditions. The drug is liable to oxidative, acidic, and alkaline degradation and showed significant stability against thermal degradation. Mass spectrometry identified the degradation products and guided suggestion of the degradation patterns. Interestingly, while inspecting the UV-absorption spectra, we observed no absorbance at 270 nm for the products of the three degradation pathways (c.f. intact MPV). Direct spectrophotometry seemed a solution that perfectly fit the purpose of the stability assay method in our case. It avoids sophisticated instrumentation and complex mathematical data manipulation. The method determined MPV accurately (100.32% ± 1.62) and selectively (99.49% ± 1.63) within the linear range of 1.50 × 10-5-4.0 × 10-4 M and down to a detection limit of 0.48 × 10-5 M. The proposed method is simple and does not require any preliminary separation or derivatization steps. The procedure proved its validity as per the ICH recommendations. The specificity was assessed in the presence of up to 90% degradation products. The study evaluated the greenness profile of the proposed analytical procedure using the National Environmental Methods Index (NEMI), the Analytical Eco-Scale, and the Green Analytical Procedure Index (GAPI). The three metrics unanimously agreed that the developed procedure results in a greener profile than the reported method. The method investigated the degradation reactions' kinetics and evaluated the reaction order, rate constant, and half-life time for each degradation process.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

DTI of the Olfactory Bulb in COVID-19-Related Anosmia: A Pilot Study.

This study aimed to assess the utility of DTI in the detection of olfactory bulb dysfunction in COVID-19-related anosmia. It was performed in 62 patients with COVID-19-related anosmia and 23 controls. The mean diffusivity and fractional anisotropy were calculated by 2 readers. The difference between the fractional anisotropy and mean diffusivity values of anosmic and control olfactory bulbs was statistically significant (P = .001). The threshold of fractional anisotropy and mean diffusivity to differentiate a diseased from normal olfactory bulb were 0.22 and 1.5, with sensitivities of 84.4% and 96.8%, respectively, and a specificity of 100%.

Designing a new fast solution to control isolation rooms in hospitals depending on artificial intelligence decision.

Decreasing the COVID spread of infection among patients at physical isolation hospitals during the coronavirus pandemic was the main aim of all governments in the world. It was required to increase isolation places in the hospital's rules to prevent the spread of infection. To deal with influxes of infected COVID-19 patients' quick solutions must be explored. The presented paper studies converting natural rooms in hospitals into isolation sections and constructing new isolation cabinets using prefabricated components as alternative and quick solutions. Artificial Intelligence (AI) helps in the selection and making of a decision on which type of solution will be used. A Multi-Layer Perceptron Neural Network (MLPNN) model is a type of artificial intelligence technique used to design and implement on time, cost, available facilities, area, and spaces as input parameters. The MLPNN result decided to select a prefabricated approach since it saves 43% of the time while the cost was the same for the two approaches. Forty-five hospitals have implemented a prefabricated solution which gave excellent results in a short period of time at reduced costs based on found facilities and spaces. Prefabricated solutions provide a shorter time and lower cost by 43% and 78% in average values respectively as compared to retrofitting existing natural ventilation rooms.

Synthesis of novel pyridine and pyrimidine thioglycoside phosphoramidates for the treatment of COVID-19 and influenza A viruses.

A novel series of pyridine, cytosine, and uracil thioglycoside analogs (4a-i, 9a,b, and 13a,b, respectively) and their corresponding phosphoramidates (6a-I, 10a,b, and 14a,b, respectively) were synthesized and assessed for their antiviral inhibitory activities in a dual-pathogen screening protocol against SARS-CoV-2 and influenza A virus (IAV). MTT cytotoxicity (TC50) and plaque reduction assays were used to explore inhibition and cytotoxicity percentage values for H5N1 influenza virus strain and the half-maximal cytotoxic concentration (CC50) and inhibitory concentration (IC50) for SARS-CoV-2 virus. Most of the tested compounds demonstrated dose-dependent inhibition behavior. Both cytosine thioglycoside phosphoramidates 10a and 10b exhibited the most potent profiles with 83% and 86% inhibition at 0.25 µM concentration against H5N1 and IC50 values of 12.16 µM, 14.9 µM against SARS-CoV-2, respectively. Moreover, compounds 10a and 10b have been shown to have the highest selectivity index (SI) among all the tested compounds against SARS-CoV-2 with 28.2 and 26.9 values, respectively.

Neurological problems in the context of COVID-19 infection in Egypt. A multicenter retrospective analysis.

BACKGROUND: COVID-19 infection has spread so fast in both low- and high-income countries. In December 2019, an outbreak of a respiratory disease occurred in China, and later, it involved different countries. Acute neurological insults are more likely to occur in severely infected patients. METHODS: We tried to evaluate patients with selective criteria including, the age of participants 18 and older with a confirmed diagnosis of SARS-CoV-2, and developed neurological complications post COVID-19 infection. An overall data of 1500 patients were collected from neurological and primary health care departments. About 970 of them had neurological problems. Patients-related data were gathered and assembled from the patients' records at participating hospitals from the Ministry of Health and university hospitals. RESULTS: We presented the results according to several variables including, regional distribution, reasons of presentation, neurological complications, follow-ups, and survival outcome. CONCLUSIONS: To our knowledge, we conducted the first retrospective analysis for neurological problems related to COVID-19 infection in Egypt. COVID-19 patients present with a variety of central and peripheral neurological symptoms, the pathogenic mechanisms of which have not been explained. Robust investigations of the neurological presentations of COVID-19 infection should be recruited for better understanding of the possible association. Moreover, further explaining the pathophysiologic mechanisms will help in designing proper treatment plans.

Cardiac involvement in hospitalized patients with COVID-19 and its incremental value in outcomes prediction.

Recent reports linked acute COVID-19 infection in hospitalized patients to cardiac abnormalities. Studies have not evaluated presence of abnormal cardiac structure and function before scanning in setting of COVD-19 infection. We sought to examine cardiac abnormalities in consecutive group of patients with acute COVID-19 infection according to the presence or absence of cardiac disease based on review of health records and cardiovascular imaging studies. We looked at independent contribution of imaging findings to clinical outcomes. After excluding patients with previous left ventricular (LV) systolic dysfunction (global and/or segmental), 724 patients were included. Machine learning identified predictors of in-hospital mortality and in-hospital mortality + ECMO. In patients without previous cardiovascular disease, LV EF < 50% occurred in 3.4%, abnormal LV global longitudinal strain (< 16%) in 24%, and diastolic dysfunction in 20%. Right ventricular systolic dysfunction (RV free wall strain < 20%) was noted in 18%. Moderate and large pericardial effusion were uncommon with an incidence of 0.4% for each category. Forty patients received ECMO support, and 79 died (10.9%). A stepwise increase in AUC was observed with addition of vital signs and laboratory measurements to baseline clinical characteristics, and a further significant increase (AUC 0.91) was observed when echocardiographic measurements were added. The performance of an optimized prediction model was similar to the model including baseline characteristics + vital signs and laboratory results + echocardiographic measurements.

Cytokine profile in Egyptian children and adolescents with COVID-19 pneumonia: A multicenter study.

BACKGROUND: To date, the cytokine profile in children and adolescent with novel coronavirus disease 2019 (COVID-19) has not been reported. OBJECTIVES: We investigated serum levels of a panel of key cytokines in children and adolescent with COVID-19 pneumonia with a primary focus on "cytokine storm" cytokines such as interleukin (IL)-1ß, IL-6, IL-17, IL-2, IL-4, IL-10, interferon (IFN-γ), tumor necrosis factor (TNF)-α, and two chemokines interferon-inducible protein-10 (IP-10) and IL-8. We also studied whether these cytokines could be potential markers for illness severity in COVID-19 pneumonia. METHODS: Ninety-two symptomatic patients aged less than 18 years with confirmed COVID-19 pneumonia and 100 well-matched healthy controls were included in this multi-center study. For all patients, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory fluid specimens was detected by real-time reverse-transcriptase polymerase chain reaction. We measured serum concentrations of studied cytokines by using flow cytometry. RESULTS: Patients with COVID-19 had significantly higher median IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 serum levels than did control children (all p < 0.01). Patients with severe COVID-19 pneumonia had significantly higher median IL-1ß, IL-6, and IP-10 serum levels as compared with those with moderate COVID-19 pneumonia; all p < 0.01. ROC analysis revealed that three of the studied markers (IL-6, IL-1ß, and IP-10) could predict severe COVID-19 pneumonia cases with the largest AUC for IL-6 of 0.893 (95% confidence interval: 0.84-0.98; p < 0.01). CONCLUSION: Our study shows that pediatric patients with COVID-19 pneumonia have markedly elevated serum IL-1ß, IL-6, IL-8, IL-10, IL-17, TNF-α, and IP-10 levels at the initial phase of the illness indicating a cytokine storm following SARS-CoV-2 infection. Moreover, serum IL-6, IL-1ß, and IP-10 concentrations were independent predictors for severe COVID-19 pneumonia.

Analyzing outcomes of neurosurgical operations performed before and during the COVID-19 pandemic in Egypt. A matched single-center cohort study.

BACKGROUND: Since the emergence of the first COVID-19 case in Wuhan, the virus affected several health care systems. Globally, the COVID-19 has a transforming effect on health care provision. Substantial evidence was clear that the global surgical services were impacted. The field of neurosurgery was primarily affected, and most elective surgeries were suspended. There are no current reports from Egypt that describe the mortality outcome of neurosurgical procedures in the context of the pandemic. METHODS: We performed that study at a large tertiary center in Egypt (Cairo University Hospital). It is a single-center matched cohort study. RESULTS: Our results examined about 346 patients earlier during the COVID-19 pandemic. About 46 (13.29%) were unmatched, so we excluded them from the final analysis of the data. About 300 patients' were matched to 304 patients' before the pandemic in 2019. The mortality outcome of neurosurgical interventions was higher during the pandemic. CONCLUSIONS: Amid the COVID-19 pandemic, the mortality outcome of neurosurgical procedures was higher than on regular days at our center. The anesthesia time was prolonged while the operation time was shortened. We strongly suggest further multicenter studies to assess the effect of COVID-19 on neurosurgical mortality and functional outcome.

Geographic classification and identification of SARS-CoV2 from related viral sequences

The COVID-19 pandemic has introduced to mild the risks of deadly epidemic-prone illnesses sweeping our globalized planet. The pandemic is still going strong, with additional viral variations popping up all the time. For the close to future, the international response will have to continue. The molecular tests for SARS-CoV-2 detection may lead to False-negative results due to their genetic similarity with other coronaviruses, as well as their ability to mutate and evolve. Furthermore, the clinical features caused by SARS-CoV-2 seem to be like the symptoms of other viral infections, making identification even harder. We constructed seven hidden Markov models for each coronavirus family (SARS-CoV2, HCoV-OC43, HCoV-229E, HCoV-NL63, HCoV-HKU1, MERS-CoV, and SARS-CoV), using their complete genome to accurate diagnose human infections. Besides, this study characterized and classified the SARS-CoV2 strains according to their different geographical regions. We built six SARS-CoV2 classifiers for each world's continent (Africa, Asia, Europe, North America, South America, and Australia). The dataset used was retrieved from the NCBI virus database. The classification accuracy of these models achieves 100% in differentiating any virus model among others in the Coronavirus family. However, the accuracy of the continent models showed a variable range of accuracies, sensitivity, and specificity due to heterogeneous evolutional paths among strains from 27 countries. South America model was the highest accurate model compared to the other geographical models. This finding has vital implications for the management of COVID-19 and the improvement of vaccines.