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1.
Journal of Population Therapeutics and Clinical Pharmacology ; 30(9):e169-e177, 2023.
Article in English | EMBASE | ID: covidwho-20243672

ABSTRACT

Self-medication is a widespread public health concern. University students are likely to be more prone to it since self-medication rates increase with educational level. Studies have shown that self-medication rates vary among academics belonging to different faculties, and medical students have the highest self-medication rates. However, it is unknown whether this holds in a vulnerable situation, such as the COVID-19 pandemic. It is also unknown whether differences in technical knowledge of drugs influence self-medication rates among students. Thus, this study analyzes and compares prophylactic self-medication among graduate students of different faculties in the context of the COVID-19 pandemic. This cross-sectional observational study was conducted at a private university in southern Brazil. Students from the medicine, law, life sciences, and fine arts faculties were surveyed, and their responses were compared using a chi-square test. Among 396 respondents, 29.5% reported using preventive medication for COVID-19, and medical students were the least likely to do so. The self-medication rate was 13.6% among respondents, and self-medication did not differ significantly between students of different faculties. Of the students who self-medicated 63% reported having studied the medication before using them. Furthermore, the media did not induce drug use among 81.8% respondents. These results show that medical students used fewer preventive medications during the pandemic and refute the assertion that self-medication rates are higher among medical students. They also show that self-medication rates during the pandemic were significantly lower than those before the pandemic. These revelations show a new aspect of self-medication.Copyright © 2021 Muslim OT et al.

2.
Journal of Parenteral and Enteral Nutrition ; 47(Supplement 2):S13-S15, 2023.
Article in English | EMBASE | ID: covidwho-2322925

ABSTRACT

Background: Total parenteral nutrition (TPN) is a life-saving therapy for patients with chronic intestinal failure. TPN typically consists of macronutrients (amino acids, dextrose, and lipids) as well as micronutrients (multi-vitamins [MVI] and trace elements) to meet fluid, calorie, and micronutrient needs. With the early years of PN administration, multiple deficiencies were noted leading to guidelines regarding need for daily use of essential trace element and MVI preparation for parenteral use. Unfortunately, during the last few years we have seen multiple shortages of PN related supplies including the most recent shortage of parenteral MVI preparation. Major organizations such as ASPEN have developed recommendations regarding management of shortages, however their clinical impact has not been fully evaluated. The current study evaluated the impact of MVI shortage on change in clinical practice and the prevalence of deficiency. Method(s): A retrospective review of electronic medical records for patients who received TPN during time of shortage in IV multivitamins supply due to COVID-19 crisis between January 2021 and June 2021. In our program, the shortage affected one TPN supplier. We included patients who received their TPN from affected supplier and who were tested for micronutrients including Vitamins A, B12, C, and D in the 6 months preceding the shortage in supply (period 1) as well as during the shortage period (period 2). Period 1 was defined as from July 1, 2020, to December 31, 2020, and period 2 was defined as from January 1, 2021, to June 30, 2021. In addition to baseline clinical characteristics, we captured changes in studied micronutrients. Result(s): Current retrospective analysis of a prospectively maintained database noted 21 patients (mean age of 63.3 +/- 13.8, 62% female) were impacted by MVI shortage during study period (Table 1). Most common primary diagnosis was Crohn's disease (33.3%) followed by enterocutaneous fistula (19%), and gastrointestinal dysmotility (14.3%). In 19/21 (90%) patients, MVI was administered 3 days per week in PN. In the remaining two patients who had short bowel,MVI was continued 7 days per week. Additionally, 19/21 (90%) patients also were supplemented orally with Vitamin D (17/21), Vitamin B12 (5/21), MVI (3/21), Vitamin C (1/21). There was a decline in average Vitamin C levels between the two study periods (Table 2) with a trend towards a decline in average 25-hydroxy vitamin D levels, while mean vitamin A and B12 levels did not change significantly. There was a significant increase in Vitamin D and C deficiencies, while no increase in deficiencies in Vitamin E, A, and B12 levels was noted (Figure 1). Conclusion(s): Unfortunately, shortages of key PN related supplies have become commonplace in the last few years. The most recent shortage affected MVI supplies. Our group managed the shortage through a combination of reduction of parenteral MVI administration to 3 days per week along with additional supplementation of specific micronutrients orally. Although with this strategy, there was an increase in Vitamin D and C levels falling below reference range, no significant deficiencies were noted. (Table Presented).

3.
Journal of Research in Pharmacy ; 26(7):1960-1968, 2022.
Article in English | EMBASE | ID: covidwho-2299762

ABSTRACT

The corona virus disease 2019 (COVID-19) pandemic has increased the interest in self-care strategies, including self-medication. Medical students, as future health practitioners, learn more about medications than other students. This study aimed to describe self-medication practices for preventing COVID-19 among medical students at Universitas Islam Indonesia. This observational study used a cross-sectional design and was undertaken in November- December 2020. The study sample included 336 undergraduate medical students determined using a consecutive sampling technique based on inclusion and exclusion criteria. Data were collected using an online questionnaire about self-medication practices in the preceding 3 months. Among a total of 336 students, 137 (41%) reported using self-medication intending to prevent COVID-19, and 126 (92%) of these 137 took preventive supplements, mainly vitamins C, D, and E, and omega-3. Seven students reported the use of zinc, mainly in combination with other vitamins. Students who practiced self-medication lived closer to people confirmed with COVID-19, washed their hands more often, and desinfected their belongings more frequently than their counterparts (p<0.05). The mean duration for consuming vitamins was 11-16 days. Forty students (29%) used herbal medicine to prevent COVID-19;ginger, turmeric, honey, black seed, cutcherry, and Curcuma were the most often consumed herbal remedies. Fourteen students (10%) reported taking over-the-counter medications to relieve symptoms related to COVID-19, including antipyretic, analgesic, antiseptic, antihistamine, decongestant, antitussive, and expectorant medications. Most respondents (82%) purchased their medications at pharmacies, and 11 (9%) obtained them from online shops. These findings show the high rate of self-medication using vitamins and herbal remedies for COVID-19 prevention among university medical students. Further studies are needed to explore students' knowledge about the risks of self-medication including the use of herbal medicines.Copyright © 2022 Marmara University Press.

4.
Current Traditional Medicine ; 9(5) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-2256455

ABSTRACT

Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.

5.
Coronaviruses ; 3(6) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2280701

ABSTRACT

Fruit, vegetables, and green tea contain quercetin (a flavonoid). Some of the diet's most signifi-cant sources of quercetin are apples, onions, tomatoes, broccoli, and green tea. Antioxidant, anticancer, anti-inflammatory, antimicrobial, antibacterial, and anti-viral effects have been studied of quercetin. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, ribonucleic acid (RNA) polymer-ase, and other essential viral life-cycle enzymes are all prevented from entering the body by quercetin. Despite extensive in vitro and in vivo investigations on the immune-modulating effects of quercetin and vitamin C treatment. 3-methyl-quercetin has been shown to bind to essential proteins necessary to convert minus-strand RNA into positive-strand RNAs, preventing the replication of viral RNA in the cytoplasm. Quercetin has been identified as a potential SARS-CoV-2 3C-like protease (3CLpro) suppressor in recent molecular docking studies and in silico assessment of herbal medicines. It has been demonstrated that quercetin increases the expression of heme oxygenase-1 through the nuclear factor erythroid-related factor 2 (Nrf2) signal network. Inhibition of heme oxygenase-1 may increase bilirubin synthesis, an endoge-nous antioxidant that defends cells. When human gingival fibroblast (HGF) cells were exposed to lipo-polysaccharide (LPS), inflammatory cytokine production was inhibited. The magnesium (Mg+2) cation complexation improves quercetin free radical scavenging capacity, preventing oxidant loss and cell death. The main objective of this paper is to provide an overview of the pharmacological effects of quercetin, its protective role against SARS-CoV-2 infection, and any potential molecular processes.Copyright © 2022 Bentham Science Publishers.

6.
European Respiratory Journal Conference: European Respiratory Society International Congress, ERS ; 60(Supplement 66), 2022.
Article in English | EMBASE | ID: covidwho-2280478

ABSTRACT

Concomitant pathology is a risk factor for severe COVID-19. Bilateral changes characteristic of sarcoidosis onCTscan can also occur with coronavirus infection.The purpose of the study: based on our own data to study the features of the course of a new coronavirus infectionin patients with lung sarcoidosis.Materials and methods: 47 patients have been under observation which accounted for 22.4% of the total number ofobserved patients with sarcoidosis. Concomitant pathology: cardiovascular system - 24.9%, gastrointestinal tractpathology - 23.3%, COPD and bronchial asthma in 11.7%, diabetes mellitus in 5.25%. As a basic therapy, 74.5%received GCS, 5.2% - methotrexate, 16.2% - GCS +methotrexate. In addition, 32% took vitamin E and 19.8% -pentoxifylline.Results and discussion: The average age of patients is 37.2+/-3.4 (men 12, women 35). In 8 patients - pneumoniawas not detected;in 21 patients (CT stage 1) SpO2 95.2+/- 2.4%, in 15 patients (CT stage 2) SpO2 86.0+/- 4.5%, in 4patients (CT stage 3) COVID-19 had a severe SpO2 68.1+/- 7.3%, which required treatment in the intensive care unit. Blood parameters: IL-6 - 94.3+/-7.8 (N less than 3.4 ng/ml), CRP 103.4+/-8.9 (N 0-5 mg/L), ACE 82.3+/-7.3 (N 8-52 units/L), D-dimer 485+/-20.8 (N less than 442 ng/ml), ferritin 643.4+/-10.7 (N 28-365 ng/ml), GGT 104.5+/-3.7 (N 1-55 Units/L), procalcitonin 0.17 +/- 0.01 (N less than 0.1ng/ml). Conclusion(s): based on the data obtained, a severe course of COVID-19 was noted in 6.38% of patients with sarcoidosis, the course of moderate severity in 32%. The factors contributing to the severe course include the use of cytostatics and GCS.

7.
Neumologia y Cirugia de Torax(Mexico) ; 81(1):41-51, 2022.
Article in Spanish | EMBASE | ID: covidwho-2278995

ABSTRACT

The regulation of inflammation is a complex pathophysiological process that depends on the production of oxygenated lipid derivatives essential polyunsaturated fatty acids, like omega-3 and omega-6, among which are the lipoxins resolvins and protectins, called specialized pro-resolving lipid mediators (SPM). Their activity is associated with the control of respiratory infection processes to modulate the production of proinflammatory cytokines, avoiding damage due to inflammation-associated necrosis, reducing microbial loads, and promoting tissue remodeling. Therefore, we review some of the biochemical, physiological and immunological aspects of SPM in the regulation of inflammation in respiratory infections.Copyright © 2022, Instituto Nacional de Enfermedades Respiratorias. All rights reserved.

8.
Vestnik Urologii/Urology Herald ; 10(4):32-42, 2022.
Article in Russian | EMBASE | ID: covidwho-2263783

ABSTRACT

Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon alpha-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon" rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C ("Viferon"rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon alpha-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.Copyright © Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.

9.
Vestnik Urologii/Urology Herald ; 10(4):32-42, 2022.
Article in Russian | EMBASE | ID: covidwho-2241641

ABSTRACT

Introduction. The tactics of managing and treating patients with chronic recurrent bacterial prostatitis (CRBP) in some cases is a difficult-to-treat condition for a practicing urologist. This circumstance occurs because the disease has several predisposing factors, a complex and multifaceted pathogenesis, and certain difficulties in diagnosis and treatment. Objective. To study the effectiveness of recombinant interferon α-2b medications in post-COVID-19 patients with chronic recurrent prostatitis against the background of antibiotic multi-drug resistance of microorganisms verified in prostate secretion. Materials and methods. The treatment of 52 post-COVID-19 patients with CRBP was analyzed, divided into three therapy-dependent groups. Group 1 patients (n = 18) received antibiotic therapy (ABT): Levofloxacin 500 mg q.d. PO for 28 days. Group 2 patients (n = 18) underwent combined therapy: ABT supplemented with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®” rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. Group 3 patients (n = 16) received monotherapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C ("Viferon®”rectal suppositories) 3.000.000 IU b.i.d. PR q12h for 28 days. The follow-up period was 6 months with monitoring of clinical and laboratory parameters assessed before treatment, after 1, 3 and 6 months from the start of therapy. Results. Based on the monitoring of the clinical picture and laboratory parameters, after 1 follow-up month, there was a significant decrease in the symptoms of the disease in all study groups. However, after 3 and 6 follow-up months, this trend was observed only in patients of groups 2 and 3 receiving recombinant interferon alfa-2b with an antioxidant complex (vitamins E and C). Conclusions. Strengthening the standard CRBP-therapy with recombinant interferon α-2b with an antioxidant complex of vitamins E and C makes it possible to normalize both clinical and laboratory parameters in most patients.

10.
Indian Journal of Gastroenterology Conference: 63rd Annual Conference of the Indian Society of Gastroenterology, ISGCON ; 42(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2227550

ABSTRACT

The proceedings contain 380 papers. The topics discussed include: fecal microbiota transplantation with anti-inflammatory diet followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis - a randomized controlled trial;gut microbial dysbiosis, gut barrier integrity, and severity of chronic pancreatitis: exploring a mechanistic link using an experimental model;acanthosis nigricans-a rare cutaneous association in progressive familial intrahepatic cholestasis type 3;liver mass presenting as acute cardiorespiratory failure;role of serum phosphate levels in acute-on-chronic liver failure patients to predict short-term mortality;association of liver dysfunction in corona virus disease-19 patients;diabetic with emphysematous liver abscess: a case report;non HFE hemochromatosis - the uncommon variant;granulomatous disease with hepatic involvement in a South Indian female;epidemiological profile of acute hepatitis patients hospitalized in a tertiary care center in Western India;and a prospective randomized comparative four arm intervention study of efficacy and safety of saroglitazar and vitamin E in patients with non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis - an interim analysis.

11.
Pharmaceutics ; 15(1)2023 Jan 10.
Article in English | MEDLINE | ID: covidwho-2200622

ABSTRACT

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.

12.
Annals of Phytomedicine-an International Journal ; 10:12-28, 2021.
Article in English | Web of Science | ID: covidwho-2072557

ABSTRACT

Viral infections are contagious and deadly. Many viral attacks in the past decades including COVID-19 have turned into pandemics and cost millions of lives. Treatment to virus is difficult as they transform themselves into many variants. Thus, an intelligent way of keeping oneself out of the trouble is through better nutrition that enhance immune responses. Foods that provide high quantities of nutrients are vegetables, fruits and nuts. They are rich in fibres, fats, protein, vitamins, minerals and plant bioactive compounds like phytosterols, polyphenolics, flavonoids, etc. Many studies and randomised control trials have proven their therapeutic effects and health promoting capacities. These compounds interfere with the pathways of metabolic mechanisms in the human body and work by either providing a protective scope or by destroying any harmful incomings into the body;that would disrupt the homeostasis. In this article, nuts and their nutritive components that administer healthy benefits are discussed. Almonds, cashew nuts, pistachios, peanuts, chestnuts and Brazil nuts are examined and reviewed here. The nutritional composition of these nuts and their mechanism to offer medicinal properties are explained in detail. Apart from nutritional values, these nuts are rich source of antioxidants that confer anti-inflammatory and immunomodulatory features. These activities enhance the immune responses by activating the defense mechanisms. Apart from the intake of highly nutritious diet, practising social distancing, isolation and better sanitation procedures are highly beneficial to avoid the severity of the viral attacks.

13.
Chest ; 162(4):A312, 2022.
Article in English | EMBASE | ID: covidwho-2060561

ABSTRACT

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: EVALI is an acute lung injury that occurs due to the use of e-cigarettes or vaporizer products that usually contain THC or nicotine. There was an outbreak of EVALI in 2019. This is a diagnosis of exclusion with foamy macrophages with pneumocyte vacuolization being the best diagnostic clues. (1) Vitamin E acetate laced products seem to be the causing factor. CASE PRESENTATION: A 34-year-old female presented to the emergency department due to increasing shortness of breath, fever, pleuritic chest pain, cough, and headaches for the last 9 days. Two days prior she presented to urgent care where she was given an albuterol inhaler and azithromycin. At arrival, the patient was found to have tachycardia with a rate of 120-130, afebrile, SpO2 at 96% on room air, BP at 100/59. Her initial workup was grossly normal except for an elevated WBC and elevated D-Dimer. Chest X-ray revealed opacities in the lower lungs consistent with pneumonia. CTA of the chest revealed patchy pulmonary opacities consistent with COVID pneumonia. She took three separate SARS-CoV-2 PCR tests which all came back negative. The patient underwent a large workup which included infectious disease, pulmonology, and cardiology consults. She was treated with broad-spectrum antibiotics for the presumed diagnosis of pneumonia but her condition quickly deteriorated, eventually requiring 6L of O2 via nasal cannula. Screening for a large array of bacteria, fungus, and viruses all resulted negative. Upon further discussion with the patient, she admitted to smoking a THC vaporizer every night for the last seven months and that she had recently purchased a new fluid for her THC vaporizer through the internet. Bronchoscopy was also acquired but did not show any specific findings, including being negative for eosinophils. Discontinuation of antibiotics and initiation of IV steroids treatment provided rapid improvement of the patient's condition. Based on her history of THC vaping, the clinical presentation of fever, hypoxia, her chest x-ray, and chest CT showing extensive lung infiltrates, infections were ruled out and the most likely diagnosis of EVALI was made which responded well to steroids. DISCUSSION: COVID and EVALI initially can present similarly as respiratory problems, fever, and the need for oxygen. It is important to gather history on the patient as a vaping history is needed to suspect EVALI as imaging can show a wide range from ground-glass opacities to acute hypersensitivity pneumonitis. (2) CONCLUSIONS: There are some distinguishing features of EVALI from COVID one being in EVALI there is a large increase in the white count and lastly the response to steroids is the key (2). Steroids are the primary care for someone with EVALI with most patients recovering in 1-3 days with the use of steroids. (2) Reference #1: Bierwirth, A., Orellana, G., Milazzo, E. and Hamdan, A., 2020. TETRAHYDROCANNABINOL VAPING-ASSOCIATED LUNG INJURY (EVALI): A US EPIDEMIC?. Chestnet Journal. Reference #2: MacMurdo, M., Lin, C., Saeedan, M., Doxtader, E., Mukhopadhyay, S., Arrossi, V., Reynolds, J., Ghosh, S. and Choi, H., 2020. e-Cigarette or Vaping Product Use-Associated Lung Injury. Chestnet Journal. DISCLOSURES: No relevant relationships by Narden Gorgy No relevant relationships by Matheus Moreira Sanches Peraci No relevant relationships by George Walbridge No relevant relationships by John Zakhary

14.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927796

ABSTRACT

Rationale The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits. Thus, new antivirals targeting SARS-CoV-2 are urgently needed. Methods Artificial intelligence algorithm MediKanren was used to query FDA-approved and late-stage drug compounds for potential interactions with SARS-CoV-2 proteins, coronaviruses, and host cell networks for possible antiviral activity. From this, 157 compounds were further tested in an antiviral screen against live SARS-CoV-2 for reduction in viral growth. Select compounds were further assessed for synergistic activity with remdesivir. Both in vitro and cell free systems identified tocopherol succinate compounds that inhibited the RNA-dependent RNA polymerase (RdRp). Validation of antiviral and synergistic activity was performed in primary human airway epithelial cell cultures against multiple SARS-CoV-2 variants.Results Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D-α-tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and β-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water-soluble derivatives of α- tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV- 2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp. Conclusion In summary, solubilizing modifications to α-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection.

15.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927723

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emergent coronavirus, that was first recognized in Wuhan, Hubei province, China, in December 2019. SARS-CoV-2 is a positive-sense singlestranded RNA virus that is contagious in humans. E-cigarette or vaping product use-associated lung injury (EVALI) is a type of acute lung injury of unclear pathogenesis. The two pathologies present with overlapping clinical symptoms, and imaging, making them difficult to distinguish, especially in global COVID-19 pandemic. Case report: 27-year-old female with past medical history of IBS, Diverticulitis, and anxiety presented with cough, shortness of breath, fever and fatigue. She also reported headaches and abdominal pain, she denies sick contact and recent travel but admit that she uses E cigarette more than usual due to anxiety attack. Patients initially discharge from ED but subsequently admit to hospital for worsening of symptoms possible COVID pneumonia vs community acquired pneumonia. She was persistently hypoxic and transfer to ICU for acute hypoxic respiratory failure. Labs was significant for elevated WBC while serum chemistries were unremarkable, Chest x-ray was not significant for any acute pathology. CT scan show revealed parenchymal changes consistent with bilateral upper and lower lobe ground-glass opacities. No septal change was noted, helping us rule out causes such as organizing pneumonia, lipoid pneumonia, and diffuse alveolar damage. Extensive testing for viral and bacterial infections was all negative. she has Covid19 PCR negative twice. Bronchoalveolar lavage testing was not done as patient refuse for invasive intervention. Patient started on steroids. Discussion: EVALI is thought to be a type of acute lung injury with an unknown pathogenesis. E-cigarette use, especially those containing THC and/or vitamin E acetate, is a key risk factor for developing the disease process. COVID 19 pneumonitis and EVALI have same clinical presentation, laboratory studies and images, and make challenge for physician to differentiate both pathologies. Both disease present with similar initial symptoms, including cough, shortness of breath, fevers, vomiting, diarrhea and headache. Similarly, laboratory studies may be unremarkable or elevated in both presentations and do not help distinguish between them. Furthermore, Chest X-ray and CT have very similar findings in both presentations, including diffuse hazy or consolidative opacities and ground-glass opacities, respectively. As well, both COVID-19 and EVALI are associated with worse outcomes in older adults or those with underlying chronic conditions, including cardiac and pulmonary disease.

16.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821960

ABSTRACT

Introduction and Objectives Novel SARS-CoV-2 virus has been implicated in prompting a bold immune response that leads to severe Coronavirus disease 2019 (COVID-19). Recent studies have shown that SARSCoV-2-infected monocytes and macrophages are stimulated to produce an overabundance of pro-inflammatory cytokines and chemokines to generate a cytokine storm. Cytokines in excess can contribute to local tissue inflammation and the pathogenesis of COVID-19. However, the mechanism by which SARS-CoV-2 signal macrophage-derived inflammatory response remains unclear. In the present study, we used RAW 264.7 cells, a wellcharacterized macrophage model, to study the in vitro effects of SARS-CoV-2 on reactive oxygen species (ROS) production and its potential role in the signal transduction of cytokine production. Methods The effect of SARS-CoV-2 on ROS and cytokine generation in macrophages was assessed by treating RAW 264.7 cells with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) or recombinant proteins for 24 hours. 2',7'-Dichlorodihydrofluorescein (2',7'-DCF) fluorescence analysis was utilized to quantify ROS generation within the RAW 264.7 macrophage cell line. Cell culture medium was sampled to quantify the levels of tumor necrosis factor (TNF) using enzyme-linked immunosorbent assay (ELISA). To assess the effects of SARS-CoV-2 on mitochondrial function, cells were treated with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) for 24 hrs. Mitochondria-derived superoxide was measured using the MitoSOX™ red mitochondrial superoxide indicator. Results Treatment of RAW 264.7 cells with inactivated SARS-CoV-2 viral particles or recombinant proteins stimulated ROS production. Mitochondria-derived superoxide and hydrogen peroxide production were increased in response to inactivated SARS-CoV-2 viral particles and recombinant protein exposure. The increased ROS generation is linked to macrophage activation induced by SARS-CoV-2 exposures. Along with the ROS generation, increased TNF production was observed. Conclusions The results of this study suggest that both SARS-CoV-2 viral proteins and heat-inactivated viral particle exposures cause significant generation of ROS and cytokines by RAW 264.7 cells. ROS generation and the subsequent cytokine release apparently play a significant role in the pathogenesis associated with the SARS-CoV-2 viral infection. The imbalanced cellular defense system against oxidative stress commonly associated with aging could explain the increased occurrence of more severe SARS-CoV-2 illness in seniors and in patients with underlying health conditions. Based on the results from this study, we propose that antioxidants such as N-acetyl-L-cysteine, resveratrol, or Vitamin E in combination with antiinflammatory drug could be used to control excess ROS and cytokines in patients with severe COVID-19.

17.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1867(2): 159070, 2022 02.
Article in English | MEDLINE | ID: covidwho-1596012

ABSTRACT

N-[4-hydroxyphenyl]retinamide, commonly known as fenretinide, a synthetic retinoid with pleiotropic benefits for human health, is currently utilized in clinical trials for cancer, cystic fibrosis, and COVID-19. However, fenretinide reduces plasma vitamin A levels by interacting with retinol-binding protein 4 (RBP4), which often results in reversible night blindness in patients. Cell culture and in vitro studies show that fenretinide binds and inhibits the activity of ß-carotene oxygenase 1 (BCO1), the enzyme responsible for endogenous vitamin A formation. Whether fenretinide inhibits vitamin A synthesis in mammals, however, remains unknown. The goal of this study was to determine if the inhibition of BCO1 by fenretinide affects vitamin A formation in mice fed ß-carotene. Our results show that wild-type mice treated with fenretinide for ten days had a reduction in tissue vitamin A stores accompanied by a two-fold increase in ß-carotene in plasma (P < 0.01) and several tissues. These effects persisted in RBP4-deficient mice and were independent of changes in intestinal ß-carotene absorption, suggesting that fenretinide inhibits vitamin A synthesis in mice. Using Bco1-/- and Bco2-/- mice we also show that fenretinide regulates intestinal carotenoid and vitamin E uptake by activating vitamin A signaling during short-term vitamin A deficiency. This study provides a deeper understanding of the impact of fenretinide on vitamin A, carotenoid, and vitamin E homeostasis, which is crucial for the pharmacological utilization of this retinoid.


Subject(s)
Fenretinide/pharmacology , Vitamin A/pharmacology , beta Carotene/metabolism , Animals , Body Weight/drug effects , Dioxygenases/metabolism , Intestinal Absorption/drug effects , Intestines/drug effects , Liver/drug effects , Liver/pathology , Mice, Inbred C57BL , Models, Biological , Retinol-Binding Proteins, Plasma/deficiency , Retinol-Binding Proteins, Plasma/metabolism , Vitamin A/blood , Vitamin A Deficiency/blood , Vitamin A Deficiency/pathology , Vitamin E/blood , Vitamin E/metabolism , beta Carotene/blood
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