Repurposing of drugs for combined treatment of COVID-19 cytokine storm using machine learning.

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) induced cytokine storm is the major cause of COVID­19 related deaths. Patients have been treated with drugs that work by inhibiting a specific protein partly responsible for the cytokines production. This approach provided very limited success, since there are multiple proteins involved in the complex cell signaling disease mechanisms. We targeted five proteins: Angiotensin II receptor type 1 (AT1R), A disintegrin and metalloprotease 17 (ADAM17), Nuclear Factor­Kappa B (NF­κB), Janus kinase 1 (JAK1) and Signal Transducer and Activator of Transcription 3 (STAT3), which are involved in the SARS­CoV­2 induced cytokine storm pathway. We developed machine learning (ML) models for these five proteins, using known active inhibitors. After developing the model for each of these proteins, FDA-approved drugs were screened to find novel therapeutics for COVID­19. We identified twenty drugs that are active for four proteins with predicted scores greater than 0.8 and eight drugs active for all five proteins with predicted scores over 0.85. Mitomycin C is the most active drug across all five proteins with an average prediction score of 0.886. For further validation of these results, we used the PyRx software to conduct protein-ligand docking experiments and calculated the binding affinity. The docking results support findings by the ML model. This research study predicted that several drugs can target multiple proteins simultaneously in cytokine storm-related pathway. These may be useful drugs to treat patients because these therapies can fight cytokine storm caused by the virus at multiple points of inhibition, leading to synergistically effective treatments.

Thymus vulgaris, a natural pharmacy against COVID-19: A molecular review.

Introduction: A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. Thymus vulgaris L. (TvL) is a plant with a long history in traditional medicine that has antimicrobial, antiseptic, and antiviral properties. Thymol and Carvacrol are two important biological components in Thyme that have anti-inflammatory, antioxidant, and immunomodulatory properties. This study is a molecular review on the potential effects of TvL and its active compounds on SARS-COV2 infection. Method: This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Results: Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Conclusions: Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.

Glycyrrhizin as a promising kryptonite against SARS-CoV-2: Clinical, experimental, and theoretical evidences.

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

Health effects and known pathology associated with the use of E-cigarettes.

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

SARS-Cov2 acute and post-active infection in the context of autoimmune and chronic inflammatory diseases.

The clinical and immunological spectrum of acute and post-active COVID-19 syndrome overlaps with criteria used to characterize autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Indeed, following SARS-Cov2 infection, the innate immune response is altered with an initial delayed production of interferon type I (IFN-I), while the NF-kappa B and inflammasome pathways are activated. In lung and digestive tissues, an alternative and extrafollicular immune response against SARS-Cov2 takes place with, consequently, an altered humoral and memory T cell response leading to breakdown of tolerance with the emergence of autoantibodies. However, the risk of developing severe COVID-19 among SLE and RA patients did not exceed the general population except in those having pre-existing neutralizing autoantibodies against IFN-I. Treatment discontinuation rather than COVID-19 infection or vaccination increases the risk of developing flares. Last but not least, a limited number of case reports of individuals having developed SLE or RA following COVID-19 infection/vaccination have been reported. Altogether, the SARS-Cov2 pandemic represents an unique opportunity to investigate the dangerous interplay between the immune response against infectious agents and autoimmunity, and to better understand the triggering role of infection as a risk factor in autoimmune and chronic inflammatory disease development.

Cardiovascular complications in the Post-Acute COVID-19 syndrome (PACS).

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) or coronavirus disease 2019 (COVID-19) initially surfaced in December 2019 from Wuhan, China, sweeping the world with various strains, forcing the WHO to declare a pandemic epidemic in March 2020. Furthermore, COVID-19 manifests with a wide array of presentations from fever and fatigue to severe respiratory and cardiovascular complications. Post-COVID-19 syndrome is poorly understood affecting COVID-19 survivors at all levels of disease severity. The disease is most associated with post-discharge dyspnea and fatigue. However, other persistent symptoms as chest pains, palpitations, smell, and taste dysfunctions. Patients with high concentrations of CRP and creatinine in the acute phase of Covid-19 are more prone to cardiac sequelae. Therefore, high levels of cardiac-sensitive troponin and hypokalaemia can also be used for risk stratification. Furthermore, Cardiac damage can manifest as myocarditis, pericarditis, rhythm abnormalities. The use of different diagnostic modalities like electrocardiogram (ECG), echocardiogram, and cardiac magnetic resonance imaging (MRI)(CMR) to evaluate the myocardial damage were studied. However, Cardiovascular complications are a common manifestation of PASC, classification of severity of cardiac symptoms and the emergence of CMR as a diagnostic tool needs more evidence.

Prognostic value of biochemical parameters among severe COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

A cross-sectional study of gastrointestinal manifestations in COVID-19 Egyptian patients.

BACKGROUND: The latest novel corona virus disease (COVID-19) pandemic shows a significant health concern. We aimed to study the prevalence of gastrointestinal symptoms among COVID-19 Egyptian patients. METHODS: A cross-sectional study was carried out on 860 patients with COVID-19 infection classified according to Ministry of Health Program (MOHP) into three groups (280 patients with mild infection, 258 patients with moderate disease and 322 patients with severe disease). All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest) and other investigations when needed in some patients e.g., upper gastro-intestinal (GI) endoscopy, abdomino-pelvic ultrasound and ECHO. RESULTS: Gastro-intestinal symptoms were present in 27.2% of the studied patients. The most common reported GIT symptoms were vomiting, diarrhea, abdominal/gastric pain, followed by nausea. GIT symptoms presence was significantly higher in severe cases in comparison to mild or moderate cases. C-reactive protein (CRP), serum ferritin, Aspartate aminotransferase (AST), bilirubin, and creatinine were significantly associated with the presence of GI symptoms. CONCLUSIONS: GI symptoms are prevalent among COVID-19 patients, the most common were vomiting and diarrhea and were associated with COVID-19 severity.

Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program.

BACKGROUND: There is an incomplete understanding of the risk of COVID-19 infection in atopic dermatitis (AD) patients. OBJECTIVE: To evaluate the risk of COVID-19 infection in AD patients in a large, diverse cohort. METHODS: A case-control study of the All of Us cohort to analyze the association between AD and COVID-19. Comorbidities and risk factors were compared between cases and controls using multivariable analyses. RESULTS: In a cohort of 11,752 AD cases with 47,008 matched controls, AD patients were more likely to have a COVID-19 diagnosis (4.2% vs 2.8%, P < .001). AD remained significantly associated with COVID-19 in multivariable analysis (odds ratio, 1.29; P < .001) after adjusting for demographic factors and comorbidities. LIMITATIONS: Ascertainment of AD and COVID-19 cases using electronic health records and lack of clinical data on AD severity or therapy and COVID-19 outcomes. CONCLUSION: AD is associated with increased odds of COVID-19 infection even after controlling for common comorbidities.

The risk factor for instability metabolic health and severity.

Coronavirus disease -19 (COVID-19) pandemic has extended from late 2019 and continues to this day. The degree of the disease is related to some factors, including age and comorbidities. Obesity is now more widely considered as a main factor of infection, mainly because it has been shown that individuals who are obese have a more severe course of infection with COVID-19. This review study summarized the relationship between the risk of obesity and COVID-19 and detected a difference in reporting from the period of the first pandemic in China to more recent studies. Obesity is a risk factor for developing signs and symptoms of patients with COVID-19 and this review will benefit clinicians by recognizing the role of obesity when giving COVID-19 diagnosis, follow-up, and treatment programs.

Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial.

COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).

Can l-carnitine reduce post-COVID-19 fatigue?

A significant number of patients infected with the new coronavirus suffer from chronic fatigue syndrome after COVID-19, and their symptoms may persist for months after the infection. Nevertheless, no particular treatment for post-disease fatigue has been found. At the same time, many clinical trials have shown the effectiveness of l-carnitine in relieving fatigue caused by the treatment of diseases such as cancer, MS, and many other diseases. Therefore, it can be considered as a potential option to eliminate the effects of fatigue caused by COVID-19, and its consumption is recommended in future clinical trials to evaluate its effectiveness and safety.