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1.
J Ayurveda Integr Med ; 13(1): 100350, 2022.
Article in English | MEDLINE | ID: covidwho-1838945

ABSTRACT

SARS-CoV-2 infection associated respiratory disease- COVID-19 has evolved into a pandemic but, being a new form of virus, pathogenesis of disease causation is not fully understood and drugs and vaccines against this virus are still being tested so that no effective drugs or vaccines have been advised by regulatory authority. In this context, the Ministry of AYUSH, Government of India has recommended 'Ayush Kwath' to improve the immunity and combat the infection. Our objective of this literature review is to review the role of immunity in pathogenesis of COVID-19 and role of Ayush Kwath against the virus and regulation of immunity. Current review was conducted using a search of available literature on COVID-19 and immunity, Vyadhikshamatwa, Ayurveda and COVID-19, Rasayana, Coronavirus, SARS-CoV-2, immunomodulatory effects of medicinal plants; Tulsi/Holy Basil/Ocimum sanctum, Dalchini/Cinnamon/Cinnamomum zeylanicum, Sunthi/Ginger/Zingiber officinale and Marich/Black Pepper/Piper nigrum. Ayurveda, being an ancient science have both medicinal and cultural values and had stimulated our kitchen and influenced what we ate in different seasons and the remedies we used for common ailments. Herbs such as Tulsi, Marich, Sunthi, Dalchini are the most commonly used and easily available drugs in home. Thus, Ayush Kwath due to its immune-modulatory, antiviral, anti-oxidant, anti-inflammatory, anti-platelet, anti-atherosclerotic, hepato-protective, reno-protective properties; seems to be effective in immuno-regulation for controlling viral infections like COVID-19. Further pre-clinical and clinical trials need to be done for the evaluation of safety and efficacy of this polyherbal formulation.

2.
J Ayurveda Integr Med ; 13(1): 100424, 2022.
Article in English | MEDLINE | ID: covidwho-1838955

ABSTRACT

For centuries, traditional medicines of Ayurveda have been in use to manage infectious and non-infectious diseases. The key embodiment of traditional medicines is the holistic system of approach in the management of human diseases. SARS-CoV-2 (COVID-19) infection is an ongoing pandemic, which has emerged as the major health threat worldwide and is causing significant stress, morbidity and mortality. Studies from the individuals with SARS-CoV-2 infection have shown significant immune dysregulation and cytokine overproduction. Neutrophilia and neutrophil to lymphocyte ratio has been correlated to poor outcome due to the disease. Neutrophils, component of innate immune system, upon stimulation expel DNA along with histones and granular proteins to form extracellular traps (NETs). Although, these DNA lattices possess beneficial activity in trapping and eliminating pathogens, NETs may also cause adverse effects by inducing immunothrombosis and tissue damage in diseases including Type 2 Diabetes and atherosclerosis. Tissues of SARS-CoV-2 infected subjects showed microthrombi with neutrophil-platelet infiltration and serum showed elevated NETs components, suggesting large involvement and uncontrolled activation of neutrophils leading to pathogenesis and associated organ damage. Hence, traditional Ayurvedic herbs exhibiting anti-inflammatory and antioxidant properties may act in a manner that might prove beneficial in targeting over-functioning of neutrophils and there by promoting normal immune homeostasis. In the present manuscript, we have reviewed and discussed pathological importance of NETs formation in SARS-CoV-2 infections and discuss how various Ayurvedic herbs can be explored to modulate neutrophil function and inhibit NETs formation in the context of a) anti-microbial activity to enhance neutrophil function, b) immunomodulatory effects to maintain neutrophil mediated immune homeostasis and c) to inhibit NETs mediated thrombosis.

3.
Trends Food Sci Technol ; 104: 219-234, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1791132

ABSTRACT

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

4.
Br J Pharmacol ; 178(19): 3864-3868, 2021 10.
Article in English | MEDLINE | ID: covidwho-1402887

ABSTRACT

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.


Subject(s)
COVID-19 , Sepsis , Animals , Ascorbic Acid , Humans , Multiple Organ Failure/drug therapy , SARS-CoV-2 , Sepsis/drug therapy , Sheep
5.
BMC Complement Med Ther ; 21(1): 141, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1388756

ABSTRACT

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.


Subject(s)
COVID-19/drug therapy , Echinacea , Immunologic Factors/pharmacology , Monocytes/drug effects , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Gene Expression , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Interferons/drug effects , Phytotherapy , Plant Extracts/therapeutic use
6.
Molecules ; 25(21)2020 Nov 02.
Article in English | MEDLINE | ID: covidwho-1389462

ABSTRACT

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Plant Extracts/therapeutic use , Pneumonia, Viral/drug therapy , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Air Sacs/drug effects , Air Sacs/virology , Animals , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19 , Chromatography, High Pressure Liquid/methods , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Disease Models, Animal , Fever/drug therapy , Fever/etiology , Hemorrhage/prevention & control , Humans , Interleukin-6/metabolism , Kidney/drug effects , Necrosis/pathology , Necrosis/prevention & control , Pandemics , Phytotherapy , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Respiratory Mucosa/transplantation , Transcriptional Activation/drug effects , Tumor Necrosis Factor-alpha/metabolism , Zebrafish
7.
Front Endocrinol (Lausanne) ; 11: 569241, 2020.
Article in English | MEDLINE | ID: covidwho-1389156

ABSTRACT

The clinical hallmarks of infections caused by critical respiratory viruses consist of pneumonia, which can progress to acute lung injury (ALI), and systemic manifestations including hypercoagulopathy, vascular dysfunction, and endotheliitis. The disease outcome largely depends on the immune response produced by the host. The bio-molecular mechanisms underlying certain dire consequences of the infection partly arise from an aberrant production of inflammatory molecules, an event denoted as "cytokine storm". Therefore, in addition to antiviral therapies, molecules able to prevent the injury caused by cytokine excess are under investigation. In this perspective, taking advantage of melanocortin peptides and their receptors, components of an endogenous modulatory system that exerts marked anti-inflammatory and immunomodulatory influences, could be an effective therapeutic strategy to control disease evolution. Exploiting the melanocortin system using natural or synthetic ligands can form a realistic basis to counteract certain deleterious effects of respiratory virus infections. The central and peripheral protective actions exerted following melanocortin receptor activation could allow dampening the harmful events that trigger the cytokine storm and endothelial dysfunction while sustaining the beneficial signals required to elicit repair mechanisms. The long standing evidence for melanocortin safety encourages this approach.


Subject(s)
COVID-19/drug therapy , Receptors, Melanocortin/agonists , Respiratory Tract Infections/drug therapy , Acute Lung Injury/drug therapy , Animals , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokines/metabolism , Humans , Melanocyte-Stimulating Hormones/metabolism , Respiratory Tract Infections/etiology , Respiratory Tract Infections/metabolism
8.
Phytother Res ; 35(8): 4258-4283, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1355894

ABSTRACT

Emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, COVID-19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products-based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID-19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus-mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS-CoV-2 disease.


Subject(s)
COVID-19 , Cytokine Release Syndrome , Flavonoids/therapeutic use , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokines , Humans , Pandemics
9.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1257893

ABSTRACT

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Retinal Diseases/chemically induced , Adult , Anti-Inflammatory Agents/therapeutic use , Female , Humans , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Visual Acuity
10.
Lancet Healthy Longev ; 2(1): e34-e41, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1290035

ABSTRACT

BACKGROUND: Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist. METHODS: In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use. FINDINGS: 6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782-1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777-1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650-0·951) and propensity matching (OR 0·759, 95% CI 0·601-0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82-1·14; p=0·689 by Cox proportional hazards). INTERPRETATION: Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive. FUNDING: National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.

11.
Eur Respir J ; 59(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1264121

ABSTRACT

BACKGROUND: Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR test were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice-daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14). RESULTS: After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3-11) DAOH14 versus 9.0 (7-10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six patients receiving placebo (p=0.57). CONCLUSIONS: The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.


Subject(s)
COVID-19 , Hydroxychloroquine , Adolescent , Adult , Azithromycin , COVID-19/drug therapy , Double-Blind Method , Humans , SARS-CoV-2 , Treatment Outcome
12.
Pharm Biol ; 59(1): 696-703, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1263613

ABSTRACT

CONTEXT: COVID-19 is a novel coronavirus that causes a severe infection in the respiratory system. Nigella sativa L. (Ranunculaceae) is an annual flowering plant used traditionally as a natural food supplement and multipurpose medicinal agent. OBJECTIVE: The possible beneficial effects of N. sativa, and its constituent, thymoquinone (TQ) on COVID-19 were reviewed. METHODS: The key words including, COVID-19, N. sativa, thymoquinone, antiviral effects, anti-inflammatory and immunomodulatory effects in different databases such as Web of Science (ISI), PubMed, Scopus, and Google Scholar were searched from 1990 up to February 2021. RESULTS: The current literature review showed that N. sativa and TQ reduced the level of pro-inflammatory mediators including, IL-2, IL-4, IL-6, and IL-12, while enhancing IFN-γ. Nigella sativa and TQ increased the serum levels of IgG1 and IgG2a, and improved pulmonary function tests in restrictive respiratory disorders. DISCUSSION AND CONCLUSIONS: These preliminary data of molecular docking, animal, and clinical studies propose N. sativa and TQ might have beneficial effects on the treatment or control of COVID-19 due to antiviral, anti-inflammatory and immunomodulatory properties as well as bronchodilatory effects. The efficacy of N. sativa and TQ on infected patients with COVID-19 in randomize clinical trials will be suggested.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Benzoquinones/pharmacology , COVID-19/drug therapy , Nigella sativa , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/isolation & purification , Antiviral Agents/isolation & purification , Benzoquinones/isolation & purification , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Cytokines/metabolism , Humans , Immune System/drug effects , Immune System/immunology , Immune System/metabolism , Immune System/virology , Inflammation Mediators/metabolism , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/virology , Nigella sativa/chemistry , Plant Extracts/isolation & purification , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
13.
J Pharm Pract ; : 8971900211015052, 2021 Jun 08.
Article in English | MEDLINE | ID: covidwho-1261249

ABSTRACT

INTRODUCTION: The pathophysiology for Coronavirus Disease 2019 (COVID-19) infection is characterized by cytokine oxidative stress and endothelial dysfunction. Intravenous (IV) vitamin C has been utilized as adjuvant therapy in critically ill patients with sepsis for its protective effects against reactive oxygen species and immunomodulatory effects. The primary objective of this study was to evaluate the effects of IV vitamin C in critically ill patients with COVID-19 infection. METHODS: Retrospective observational cohort study with propensity score matching of intensive care unit (ICU) patients who received 1.5 grams IV vitamin C every 6 hours for up to 4 days for COVID-19 infection. The primary study outcome was in-hospital mortality. Secondary outcomes included vasopressor requirements in norepinephrine equivalents, ICU length of stay, and change in Sequential Organ Failure Assessment (SOFA) score. RESULTS: Eight patients received IV vitamin C and were matched to 24 patients. Patients in the IV vitamin C group had higher rates of hospital mortality [7 (88%) vs. 19 (79%), P = 0.049]. There was no difference in the daily vasopressor requirement in the treatment group or between the 2 groups. The mean SOFA scores post-treatment was higher in the IV vitamin C group (12.4 ± 2.8 vs. 8.1 ± 3.5, P < 0.005). There was no difference in ICU length of stay between the treatment and control groups. CONCLUSION: Adjunctive IV vitamin C for the management of COVID-19 infection in critically ill patients may not decrease the incidence of mortality, vasopressor requirements, SOFA scores, or ventilator settings.

14.
Expert Rev Anti Infect Ther ; 20(1): 17-21, 2022 01.
Article in English | MEDLINE | ID: covidwho-1258702

ABSTRACT

INTRODUCTION: Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach. AREAS COVERED: We analyze selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the results that suggested a potential survival benefit of low-dose aspirin and colchicine when used for COVID-19. EXPERT OPINION: Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that are unfortunately currently at best of second choice after paracetamol, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their anti-inflammatory and immunomodulatory properties. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Drug Repositioning , Interleukin-6/antagonists & inhibitors , Nitro Compounds/therapeutic use , Thiazoles/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/immunology , Humans , Interferons/immunology , Interleukin-6/immunology , Observational Studies as Topic , SARS-CoV-2/pathogenicity
15.
Int J Mol Sci ; 22(11)2021 May 26.
Article in English | MEDLINE | ID: covidwho-1256559

ABSTRACT

Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.


Subject(s)
Ceramides/metabolism , HIV-1/metabolism , Influenza A virus/metabolism , SARS-CoV-2/metabolism , Virus Diseases/metabolism , Virus Diseases/virology , Apoptosis/drug effects , Apoptosis/immunology , Ceramides/chemistry , Gene Expression Regulation, Viral , HIV-1/pathogenicity , Humans , Immunomodulation , Influenza A virus/pathogenicity , SARS-CoV-2/pathogenicity , Virion/growth & development , Virus Diseases/immunology , Virus Internalization , Virus Replication/drug effects , Virus Replication/immunology
16.
BMC Pediatr ; 21(1): 258, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1255910

ABSTRACT

BACKGROUND: Abdominal pain and other gastrointestinal symptoms are common presenting features of multisystem inflammatory syndrome in children (MIS-C) and can overlap with infectious or inflammatory abdominal conditions, making accurate diagnosis challenging. CASE PRESENTATION: We describe the case of a 16-year-old female who presented with clinical symptoms suggestive of appendicitis and an abdominal computed tomography (CT) that revealed features concerning for appendicitis. After laparoscopic appendectomy, histopathology of the appendix demonstrated only mild serosal inflammation and was not consistent with acute appendicitis. Her overall clinical presentation was felt to be consistent with MIS-C and she subsequently improved with immunomodulatory and steroid treatment. CONCLUSIONS: We note that MIS-C can mimic acute appendicitis. This case highlights MIS-C as a cause of abdominal imaging with features concerning for appendicitis, and MIS-C should be considered in the differential for a patient with appendicitis-like symptoms and a positive COVID-19 IgG. Lab criteria, specifically low-normal white blood cell count and thrombocytopenia, appears to be of high relevance in differing MIS-C from acute appendicitis, even when appendix radiologically is dilated.


Subject(s)
Appendicitis , COVID-19 , Adolescent , Appendectomy , Appendicitis/diagnostic imaging , Child , Female , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
17.
J Transl Med ; 19(1): 234, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249559

ABSTRACT

Adipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. In this context, mesenchymal stromal/stem cells (MSCs), adipocyte mesenchymal stem cells (Ad-MSCs) and adipose-derived stem cells (ADSC) possessing potent immunomodulatory activities are proposed as a therapeutic option for the treatment of coronavirus disease 2019 (COVID-19). The COVID-19 represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which there is not actually any specific therapy. MSCs exert an immunomodulation effect due to the secretion of endogenous factors, such as vascular endothelial growth factor (VEGF), insulin growth factor (IGF), and nerve growth factor (NGF), transforming growth factor (TGF)-ß and growth differentiation factor (GDF)-11. Recent reports are promising for further studies and clinical applications of ADSCs and Ad-MSCs in COVID-19 patients. Experimental and clinical studies are exploring the therapeutic potential of both MSCs and derived-exosomes in moderating the morbidity and mortality of COVID-19. In this field, more preclinical and clinical studies are warranted to find an effective treatment for the patients suffering from COVID-19 infection.


Subject(s)
COVID-19 , Exosomes , Mesenchymal Stem Cell Transplantation , Humans , SARS-CoV-2 , Vascular Endothelial Growth Factor A
18.
Br J Pharmacol ; 178(19): 3864-3868, 2021 10.
Article in English | MEDLINE | ID: covidwho-1249399

ABSTRACT

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.


Subject(s)
COVID-19 , Sepsis , Animals , Ascorbic Acid , Humans , Multiple Organ Failure/drug therapy , SARS-CoV-2 , Sepsis/drug therapy , Sheep
19.
Front Immunol ; 12: 637553, 2021.
Article in English | MEDLINE | ID: covidwho-1247858

ABSTRACT

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.


Subject(s)
Biological Products/therapeutic use , COVID-19/drug therapy , Complementary Therapies/methods , Phytotherapy/methods , Plant Preparations/therapeutic use , SARS-CoV-2/physiology , Virus Diseases/drug therapy , Animals , Humans , Immunomodulation , Plants, Medicinal , Terpenes/therapeutic use
20.
J Genet Eng Biotechnol ; 19(1): 82, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1247615

ABSTRACT

BACKGROUND: Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. SHORT CONCLUSION: In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

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