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1.
Era's Journal of Medical Research ; 8(2):185-189, 2021.
Article in English | ProQuest Central | ID: covidwho-1964967

ABSTRACT

In China and India, Nelumbo nucífera, a perennial aquatic plant, has been used as a medicinal herb. The various sections of plants, such as leaves, seeds, flowers and rhizomes, have been reported to have beneficial effects in the treatment of pharyngopathy, pectoralgia, spermatorrhoea, leucoderma, smallpox, dysentery, cough, haematemesis, epistaxis, haemoptysis, haematuria, metrorrhagia, hyperlipidaemia, fever, cholera, hepatopathy and hyperdipsia in the traditional medicine system. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepatoprotective activity, anti-inflammatory activity, anti-fertility activity, antiarrhythmic activity, anti-fibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, antipyretic activity, immune-modulatory activity, hypoglycaemic activity, aldose reductase inhibitory activity, antibacterial, aphrodisiac activity, anti-platelet activity, cardiovascular activity, anti-obesity activity, lipolytic activity, hypo-cholesterolaemic activity, hepato-protective activity, anticancer activitydiuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. Different pharmacological activities such as anti-ischaemic activity, antioxidant activity, hepato-protective activity, anti-inflammatory activity, anti-fertility activity, anti-arrhythmic activity, antifibrosis activity, antiviral activity, anti-proliferative activity, anti-diarrhoeal activity, psychopharmacological activity, diuretic activity, antioxidant activity have been clinically evaluated for N.nucifera. A wide number of phytoprinciples from the plant have been isolated. The present review seeks to consolidate the traditional, ethno-botanical, phytochemical and pharmacological data available on N.nucifera stem and to explore its role as an immunity booster and anti-inflammatory food.

2.
Journal of Clinical and Diagnostic Research ; 16(7):WC01-WC05, 2022.
Article in English | EMBASE | ID: covidwho-1957573

ABSTRACT

Introduction: The entire world has been affected by Coronavirus disease 2019 (COVID-19) and experts all over the world are working hard to combat this global pandemic. There is a panic among people with resultant psychosocial consequences. Aim: To evaluate the fear factor of COVID-19 using Fear of COVID-19 Scale (FCV-19S) among two groups of patients, one with dermatological diseases managed with immunomodulators and second with dermatological diseases not requiring immunosuppression and also to counsel both the groups regarding the course of their disease and tailoring their visits to the hospital accordingly. Materials and Methods: This cross-sectional study was conducted from 16th January 2021 to 30th April 2021 in the Outpatient Department (OPD) of Dermatology of a tertiary care centre, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India. Consecutive 52 patients meeting the inclusion criteria, with dermatological diseases requiring long-term immunosuppressive therapy and 49 patients with dermatological diseases or cosmetic concerns not requiring immunosuppressive treatment were enrolled for the study. The obtained data was analysed using Epi Info software version 7.2.4.0. results: A total number of 101 patients were enrolled in the study with a male to female ratio of 1.7:1. Mean age of patients was 41 years (range 18-71 years). Among them, 52 (51.49%) had chronic diseases with relapsing and remitting course requiring immunomodulator drugs and 49 (48.51%) had either cosmetic concerns or diseases not requiring immunomodulation. Seventeen (16.83%) of the total patients had other co-morbidites like diabetes mellitus, hypertension, chronic kidney disease or cardiac diseases. Out of all the study participants, 3 (2.9%) had severe fear, 16 (15.8%) had moderate fear, 36 (35.6%) had mild fear and 46 (45.5%) had no fear of COVID-19. conclusion: During this pandemic time, patients need to be counselled regarding the course and management of their diseases and stress factor should also be addressed.

3.
World Journal of Gastroenterology ; 28(25):2802-2822, 2022.
Article in English | EMBASE | ID: covidwho-1957483

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.

4.
Open Access Macedonian Journal of Medical Sciences ; 10:1383-1391, 2022.
Article in English | EMBASE | ID: covidwho-1939099

ABSTRACT

BACKGROUND: No gold standard therapy was approved globally for COVID-19 pneumonia to the date of this study. The pathophysiology of SARS-CoV-2 infection displayed the predominance of hyperinflammation and immune dysregulation in inducing multiorgan damage. Therefore, the potential benefits of both immune modulation and suppression in COVID-19 have been extensively discussed as a modality to control cytokine release syndrome (CRS). Abnormally high levels of interleukin-6 (IL-6) are a common finding in COVID-19 patients with pneumonia and acute respiratory distress syndrome, so the use of IL-6 antagonist was tested as a therapeutic option in controlling the disease. Tocilizumab is a recombinant humanized anti-human IL-6 receptor monoclonal antibody that can specifically bind the membrane-bound IL-6 receptor and soluble IL-6 receptor, thereby inhibiting signal transduction. Tocilizumab is currently FDA approved for the management of rheumatoid arthritis, giant cell arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. This study is a retrospective analysis of data polled during Phase I of COVID pandemic, adopted by the isolation hospital of Kasr Al-Ainy Medical School, Cairo University, during the period from May to September 2020. AIM: The aim of this study is to evaluate tocilizumab influence in the outcome;in terms of reducing the hospital stay, risk and duration of mechanical ventilation (invasive and noninvasive), mortality, and the incidence of complications related to drugs use (secondary bacterial infection and GIT bleeding) in patients with moderate-to-severe COVID-19. METHODS: This retrospective, observational cohort study included adults (between 18 and 80 years) with moderate-to-severe COVID-19 pneumonia, who were admitted to isolation hospital of Kasr Al-Ainy Medical School, Cairo University, between May and September 2020. We segregated the patients into two groups: Group A: In addition to the standard care protocol according to the local guidelines of the Egyptian Ministry of Health and Population in that period (supplemental oxygen, steroids in a dose of 1–2 mg/kg methylprednisolone for 5–10 days, broad-spectrum antibiotics, vitamins, and prophylactic dose of anticoagulation with low-molecular-weight heparin, proton-pump inhibitor, and poly-vitamins), they received tocilizumab intravenously in a dose of 8 mg/kg bodyweight (up to a maximum of 800 mg per dose), divided in two shots 12–24 h apart. Group B: Those received the standard care protocol alone, noting that guidelines were adjusted later on according to the updated scientific publications and WHO recommendations. The primary endpoint was to evaluate the effect of different regimens in controlling the disease, the need for mechanical ventilation and its duration (either invasive or non-invasive), length of ICU stay, hospital stay, and in-hospital mortality. Comparisons between quantitative variables were done using the non-parametric Mann–Whitney U-test. For comparison of serial measurements within each patient, the non-parametric Wilcoxon signed-rank test was used. For comparing categorical data, Chi-square (2) test was performed. Exact test was used instead when the expected frequency was <5. Correlations between quantitative variables were done using Spearman correlation coefficient. RESULTS: During this period, 166 patients were admitted to ICU, suffering from severe hypoxemia with moderate to severe COVID-19 pneumonia, 10 of them were excluded (three were over 80 years old, other three had advanced stages of malignancy, two were on steroids therapy and non-invasive home ventilation due to chronic chest condition, and two were presented with MODs and deceased in <48 h from admission), thus, 156 were included in the study. Group A: Seventy-six patients (49%) received tocilizumab in addition to standard therapy, Group B: Eighty patients (51%) received standard therapy only. In Group A, the mean length of ICU stay was 8.96 days with mean length of hospital stay 13.76, compared to mean length f ICU stay 9 days in Group B (p = 0.57) and mean length of hospital stay 12.46 days (p = 0.117). In Group A, 35 patients (46%) needed non-invasive mechanical ventilation (MV),12 patients of the 35 needed invasive MV in later stage, compared to 26 patients (32%) in Group B, 14 patients of the 26 needed invasive MV in later stage (p = 0.16). In Group A, 14 patients (18.4%) needed invasive mechanical ventilation, compared to 19 patients (23.7%) in Group B (p = 0.213). In Group A, 6 (7.9%) of 76 patients died, compared to 13 (16.3%) of 80 in Group B p = 0.11. The incidence of secondary bacterial infection in Group A was 16 patients (21%) compared to 21 (26%) in Group B (p = 0.44). CONCLUSION: In this study, we did not detect statistical difference in both groups of patients coming during CRS-associated COVID-19 pneumonia, regarding (ICU stay, need for and length of MV, the incidence of secondary bacterial infection, and in-hospital mortality) for COVID-19 moderate-to-severe pneumonia.

5.
Cells ; 11(14)2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1938702

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Adult , COVID-19/therapy , Cytokine Release Syndrome , Humans , Immunity , Immunomodulation , Mesenchymal Stem Cells/metabolism , SARS-CoV-2
6.
BMC Complement Med Ther ; 22(1): 191, 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1938309

ABSTRACT

BACKGROUND: The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has a significant mortality rate of 3-5%. The principal causes of multiorgan failure and death are cytokine release syndrome and immune dysfunction. Stress, anxiety, and depression has been aggravated by the pandemic and its resultant restrictions in day-to-day life which may contribute to immune dysregulation. Thus, immunity strengthening and the prevention of cytokine release syndrome are important for preventing and minimizing mortality in COVID-19 patients. However, despite a few specific remedies that now exist for the SARS-CoV-2virus, the principal modes of prevention include vaccination, masking, and holistic healing methods, such as yoga. Currently, extensive research is being conducted to better understand the neuroendocrinoimmunological mechanisms by which yoga alleviates stress and inflammation. This review article explores the anti-inflammatory and immune-modulating potentials of yoga, along with its role in reducing risk for immune dysfunction and impaired mental health. METHODS: We conducted this narrative review from published literature in MEDLINE, EMBASE, COCHRANE databases. Screening was performed for titles and abstracts by two independent review authors; potentially eligible citations were retrieved for full-text review. References of included articles and articles of major non-indexed peer reviewed journals were searched for relevance by two independent review authors. A third review author checked the excluded records. All disagreements were resolved through discussion amongst review authors or through adjudication by a fourth review author. Abstracts, editorials, conference proceedings and clinical trial registrations were excluded. OBSERVATIONS: Yoga is a nonpharmacological, cost-effective, and safe intervention associated with several health benefits. Originating in ancient India, this vast discipline consists of postures (asanas), breathing techniques (pranayama), meditation (dhyana/dharana), and relaxation. Studies have demonstrated yoga's ability to bolster innate immunity and to inhibit cytokine release syndrome. As an intervention, yoga has been shown to improve mental health, as it alleviates anxiety, depression, and stress and enhances mindfulness, self-control, and self-regulation. Yoga has been correlated with numerous cardioprotective effects, which also may play a role in COVID-19 by preventing lung and cardiac injury. CONCLUSION AND RELEVANCE: This review paves the path for further research on yoga as a potential intervention for enhancing innate immunity and mental health and thus its role in prevention and adjunctive treatment in COVID-19.


Subject(s)
COVID-19 , Meditation , Yoga , Cytokine Release Syndrome , Humans , Immunomodulation , Mental Health
7.
Front Endocrinol (Lausanne) ; 13: 889928, 2022.
Article in English | MEDLINE | ID: covidwho-1933631

ABSTRACT

Introduction: Patients with Cushing's syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient's condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient's condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients.


Subject(s)
COVID-19 , Cushing Syndrome , Adrenocorticotropic Hormone , Aged , COVID-19/complications , COVID-19/drug therapy , Cushing Syndrome/complications , Cushing Syndrome/diagnosis , Cushing Syndrome/drug therapy , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Pandemics
8.
European Stroke Journal ; 7(1 SUPPL):35-36, 2022.
Article in English | EMBASE | ID: covidwho-1928126

ABSTRACT

Background and aims: Cerebral venous sinus thrombosis with thrombocytopenia syndrome (CVST-TTS) is a rare adverse effect of adenovirus- based SARS-CoV-2 vaccines. After the autoimmune pathogenesis of TTS was discovered, treatment recommendations were issued. The aim of this study was to evaluate if adherence to treatment recommendations was associated with lower mortality. Methods: TTS was defined according to the Brighton criteria. Cases from a prospective international CVT registry with symptom onset within 28 days of adenovirus-based SARS-CoV-2 vaccination were analysed. Treatment recommendations, following the International Society of Thrombosis and Haemostasis, included use of immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusions, unless needed for surgery. Results: Out of 178 CVT cases from 117 centres in 19 countries reported between March 29 and September 3, 2021, 95 patients fulfilled inclusion criteria. Five of 37 (14%), 13/25 (52%), and 29/33 (88%) of patients diagnosed in March, April, and from May onwards, respectively, were treated according to recommendations. Proportion of patients diagnosed in March, April, and from May onwards who received immunomodulation increased from 19/37 (51%) over 15/25 (60%) to 30/33 (90%), and the percentage of patients who were treated with heparins [26/37 (70%), 4/25 (16%), 1/33 (3%)] and platelet transfusion [15/37 (41%), 4/25 (16%), 7/33 (21%), respectively] decreased accordingly. Mortality of patients treated according to recommendations was 14/47 (30%, 95%CI 19-44%) compared to 28/48 (58%, 95%CI 44-71%) in patients not treated according to recommendations (OR 3.30, 95%CI 1.41-7.71). Conclusions: Over time, adherence to treatment recommendations improved, and mortality rate of patients with CVST-TTS decreased.

9.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927859

ABSTRACT

Rationale: Despite the availability of pharmacologic therapies, idiopathic pulmonary fibrosis (IPF) is still a clinical challenge with several unmet needs. Robust evidence supports monocytes as cellular biomarkers of progression in IPF. Yet, their precise role and whether specific subtypes might predict progression and drive disease is unknown. We reported, for the first time, that myeloidderived suppressor cells (MDSC), immature precursors of monocytes, are increased in numbers, functionally active in IPF. Monocytic MDSC is the predominant subtype in IPF, and yet, functional characterization and immune modulation properties have not been explored. Methods and Results: characterization of circulating myeloid populations in IPF by multicolor FACS confirmed the abundance of MDSC (Lin-, HLA-DRlo, CD33+, CD14+, S100A+, CD28L1+ and ICOSL+) in IPF (n=78) and fILD (n=83), also abundant in whole blood scRNA seq of severe Covid-19 patients that progressed into fibrosis, and not in mild Covid-19. Then, we prospectively followed 83 fILD patients (45% IPF, 55% non-IPF -EAA, CTD-ILD, NSIP-) over 1 year and immunophenotyped them every 3 months. Cross-sectional analysis showed that patients with a higher number circulating MDSC, had a higher GAP index (7-8) (p<0,001). Longitudinal follow-up showed that patients with constant higher circulating MDSC had lower transplant-free survival (p=0.0058). Primary isolated MDSC when co-cultured with autologous T cells induced CD8+ T cell exhaustion (PD1hi, Lag3hi, Tim3hi, TNFalpha lo, INFglo), and downregulation of co-stimulatory T cell signaling (CD28, ICOS, ITK, and LCK), preliminary data support the induction of de-novo FoxP3 Treg formation, creating a suppressive and immunosenescent microenvironment in IPF. FACS analysis of explanted lungs demonstrated the increase of tissue-resident MDSC in fibrosis (HP, NSIP, IPF) compared with donor lungs, as well as in bleomycin-induced fibrosis compared to PBS. Conclusion: Taking together, a high number of circulating MDSC reflects worse lung function and higher GAP index in cross-sectional analysis, and associates with lower transplant-free survival longitudinally. The role that immature and mature monocytes play during promotion of a suppressive microenvironment in IPF is an unexplored area that may lead to a paradigm shift in our understanding of the sequelae of exhaustion and immunosenescence, contributing to the identification of novel targets useful for therapeutic myeloid selection in IPF.

10.
American Journal of Reproductive Immunology ; 87(SUPPL 1):76, 2022.
Article in English | EMBASE | ID: covidwho-1927548

ABSTRACT

Introduction: In January 2020, the genome of the novel coronavirus, SARS-CoV-2, was sequenced, the etiologic RNA virus for COVID- 19. Several variants from the initial strain of SARS-CoV-2 have been reported, notably the Delta variant and most recently, the Omicron variant. However, how the virus affects the cellular immune system has been elusive. This study aims to investigate peripheral blood immunophenotype, natural killer (NK) cell cytotoxicity, and T helper (Th) 1/ Th2 ratios in pregnantwomen undergoing immunotherapy with a history of recurrent pregnancy losses (RPL) and repeated implantation failures (RIF). Materials and Methods: A prospective cohort study was performed on pregnant women with a history of RIF and RPL. The study group comprised 20 pregnant women with COVID-19, of whom eight had documented vaccinations. All were undergoing personalized immunemodulation and/or anticoagulation treatment. When they were diagnosed with COVID-19, immunomodulating medications were tapered off or decreased until recovery. Peripheral blood immunophenotype, NK cell cytotoxicity (NKC) at effector to target cell (E: T) ratio at 50:1 and 25:1, and Th1/Th2 cell ratios (TNF-a/IL-10, IFN-g/IL-10 producing Th cell ratios)were measured by flow cytometry within 5weeks before and after COVID-19. Statistical analysis was performed by using the student t-test. Results: Peripheral blood immunophenotypes including % CD3 (77.38 ± 2.15 % vs. 79.98 ± 1.65 %, P = 0.34), % CD19 (13.63 ± 1.63 % vs. 12.63 ± 1.79 %, P = 0.68), % CD56 (7.61 ±1.32 % vs. 6.15± 1.08 %, P = 0.40), % CD19/CD5 (4.68 ±1.41 % vs. 4.17 ± 0.72 %, P = 0.75) were not significantly different before and after COVID- 19. NKC at E: T ratio of 50:1 (Mean ±SE), before and after COVID- 19 were 21.16 ± 0.66% and 22.21 ± 1.06 % respectively (P = 0.40). NKC at E: T cell ratios of 25:1 were 15.71 ± 0.69 % and 16.44 ± 0.93 % respectively (P = 0.52). TNF-a/IL-10 (29.61 ± 2.43 vs 28.95 ±2.06, P = 0.83) and IFN-g/IL-10 (16.36 ±2.22 vs 12.61 ± 0.94, P = 0.14) producing Th1/Th2 cell ratios were comparable before and after COVID-19. Conclusions: Our findings suggest that even though patients are affected by the COVID-19 during the Omicron phase, ©2022 The Authors. American Journal of Reproductive Immunology ©2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. there were no significant flares in cellular immune responses when patients recovered from COVID-19 in not hospitalized cases.

11.
Comput Biol Med ; 148: 105814, 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1926333

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic and respiratory infection that has enormous damage to human lives and economies. It is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a non-pair-stranded positive-sense RNA virus. With increasing global threats and few therapeutic options, the discovery of new potential drug targets and the development of new therapy candidates against COVID-19 are urgently needed. Based on these premises, we conducted an analysis of transcriptomic datasets from SARS-CoV-2-infected patients and identified several SARS-CoV-2 infection signatures, among which TNFRSF5/PTPRC/IDO1/MKI67 appeared to be the most pertinent signature. Subsequent integrated bioinformatics analysis identified the signature as an important immunomodulatory and inflammatory signature of SARS-CoV-2 infection. It was suggested that this gene signature mediates the interplay of immune and immunosuppressive cells leading to infiltration-exclusion of effector memory T cells in the lungs, which is of translation relevance for developing novel SARS-CoV-2 drug and vaccine candidates. Consequently, we designed and synthesized a novel small-molecule quinoline derivative (RXn-02) and evaluated its pharmacokinetics in rats, revealing a peak plasma concentration (Cmax) and time to Cmax (Tmax) of 1.756 µg/mL and 0.6 h, respectively. Values of the area under the curve (AUC) (0-24 h) and AUC (0 h∼∞) were 18.90 and 71.20 µg h/mL, respectively. Drug absorption from the various regional segments revealed that the duodenum (49.84%), jejunum (47.885%), cecum (1.82%), and ileum (0.32%) were prime sites of RXn-02 absorption. No absorption was detected from the stomach, and the least was from the colon (0.19%). Interestingly, RXn-02 exhibited in vitro antiproliferative activities against hub gene hyper-expressing cell lines; A549 (IC50 = 48.1 µM), K-562 (IC50 = 100 µM), and MCF7 (IC50 = 0.047 µM) and against five cell lines originating from human lungs (IC50 range of 33.2-69.5 µM). In addition, RXn-02 exhibited high binding efficacies for targeting the TNFRSF5/PTPRC/IDO1/MK signature with binding affinities (ΔG) of -6.6, -6.0, -9.9, -6.9 kcal/mol respectively. In conclusion, our study identified a novel signature of SARS-CoV-2 pathogenesis. RXn-02 is a drug-like candidate with good in vivo pharmacokinetics and hence possesses great translational relevance worthy of further preclinical and clinical investigations for treating SARS-CoV-2 infections.

12.
Farmaceutski Glasnik ; 78(1-2):15-28, 2022.
Article in Croatian | EMBASE | ID: covidwho-1925189

ABSTRACT

Organ transplantation in the final stages of chronic disease or in case of acute failure is an accepted procedure of treating patients that has been developing for many years. After the organ transplantation procedure, immunosuppressive therapy is started, which strikes a balance between the modulation of the immune system in order to avoid organ rejection or the harmful effects of immunosuppression. Commonly used immunosuppressants for the treatment of transplant patients are from the group of calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (sirolimus, everolimus). Mycophenolic acid, leflunomide and glucocorticoids are used as supportive therapy, and with the discovery of biological therapy, therapeutic monoclonal antibodies directed against various cellular targets have been developed. Optimization and laboratory monitoring of immunosuppressive concentrations is necessary after transplantation in order to avoid graft rejection and the occurrence of unwanted side effects. The most commonly used methods for therapeutic drug monitoring in clinical laboratories are immunochemical methods characterized by high levels of automation but also have major shortcomings such as insufficient specificity and standardization, which is why the method of choice for therapeutic monitoring is liquid chromatography-tandem mass spectrometry whose main characteristic is specificity and selectivity. Therefore, when measuring the concentration of immunosuppressants, it is important to state the method of determination. The global spread of Coronavirus disease (COVID-19) has affected organ donation and transplantation and is actively trying to clarify the role of immunosuppressive therapy in the disease process because it is extremely difficult to strike a balance between suppressing the immune response to prevent organ rejection and control inflammation during COVID-19 disease. Given the complexity of treating the transplant population of patients with COVID-19, there is a clear need for a systemic approach to treatment, which will consequently lead to better outcomes.

13.
Diabetes ; 71, 2022.
Article in English | ProQuest Central | ID: covidwho-1923905

ABSTRACT

Background: Diabetes mellitus (DM) confers a two-fold increased risk of death from COVID-19 and overall poorer prognosis compared to the general population. Metformin is a widely used first-line antidiabetic agent with anti-inflammatory and immunomodulatory effects. Several studies report reduced COVID-19-related mortality in patients with DM on metformin. Few studies have corroborated these findings within a multiracial, multiethnic population. Methods: This was a retrospective cohort study of patients with DM admitted with COVID-19 to 1 of 3 urban academic hospitals from 1/1/20 to 5/7/20. We compared in-hospital mortality and length of stay (LOS) in COVID-19 patients with diabetes on metformin compared to those not on metformin. Patient demographic and clinical characteristics were summarized and compared between both groups. Logistic regression and linear regression analysis were applied to study the association between metformin treatment and in-hospital mortality and LOS, respectively. Results: A total of 4462 patients were identified. Overall, 46.9% were female, with a mean age of 64.4 years;41.3% were Black and 41.5% Hispanic. There were 1021 in the metformin group and 3441 in the non-metformin group. The prevalence of hypertension (58.2% vs.37.5%, P<.0001) and coronary artery disease (13.4% vs. 6.7%, P<0.0001) was higher in the metformin group compared to the non-metformin group. BMI (30.5 vs. 29.4) , HbA1c (8.2 vs. 6.5) creatinine (1.6 vs. 2.1) , and mean number of antidiabetic agents (1.2 vs. 0.22) were also significantly higher in the metformin group. The odds of death (OR 1.0, 95% CI 0.8-1.3;p=0.900) and mean LOS (p= 0.486) were not significantly different in the metformin vs. non-metformin group, after adjusting for confounding variables. Conclusion: There was no significant difference in in-hospital mortality and LOS in the metformin vs. non-metformin group. The metformin group had a significantly higher comorbidity burden, as well as higher BMI, mean HbA1c, and creatinine. Further prospective studies are needed.

14.
Journal of Young Pharmacists ; 14(2):140-155, 2022.
Article in English | EMBASE | ID: covidwho-1918025

ABSTRACT

Since December 2019 world faces a respiratory pandemic named Coronavirus disease-19 (COVID-19). COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The term epidemic was coined by Hippocrates who is considered the father of Unani medicine which is based on four humours. In the Unani System of Medicine (USM) equivalent term for the epidemic is Wabā'. In classical Unani literature symptoms of Nazla-i-Wabā'iyya and Humma-i-Wabā'iyya closely resemble the symptoms of COVID-19. Major manifestations of this outbreak are cough, fever, headache, nausea, and breathlessness. This pandemic takes place due to a change in the quality of the surrounding air. We searched different databases electronically using the terms “COVID-19 or Coronavirus”, “Wabā or infectious disease”, “Unani immunomodulators”, ''Herbal immunomodulators'', ''Anti-viral herbal drugs'', Herbal fumigation and “Nazla-i-Wabā'iyya or Nazla Wabā'ī”. We also gone through different classical textbooks of USM available in the NRIUMSD library. We reviewed the concept of Wabā', its prevention, and management strategies available in USM. We also searched antiviral, immunomodulation, fumigation activities of Unani drugs. Unani physicians advocated general measures of physical distancing, health hygiene, isolation, quarantine, and immunomodulation. As a preventive measure, various immunomodulatory drugs like Asgandh, Aam, Babuna, Gilo, Satawar, and Kalonji and antidotes such as Tiryāq Wabā'i have been described in the literature. The ingredients of Tiryāq-i-Wabā'i include Aloe barbedensis, Crocus sativus, and Commiphora myrrha. Several fumigants like Sandal, Ood, Kafoor, Loban, and Jhau are also mentioned in the management of the epidemic. For symptomatic management various antiviral, antipyretic and antitussive drugs are described well. Many evidence-based studies have already been reported for single drugs and formulations used in the USM.The Khamira Marwareed possesses antiviral, cardiotonic, and immunomodulatory activity. Single drugs such as Khaksi, Asgandh, Adusa, Chiriata, and Zanjabeel possess antipyretic, immunomodulatory, antitussive, antibacterial, and antiviral activities respectively. The knowledge from classical Unani literature and scientific researches may be useful in the prevention and management of COVID-19 like epidemic diseases. This review article aims to find out the concept of the pandemic, prevention, and management strategies existing in the USM.

15.
Internal Medicine Journal ; 52(SUPPL 1):13-14, 2022.
Article in English | EMBASE | ID: covidwho-1916175

ABSTRACT

Introduction: Since the SARS-CoV-2 (severe acute respiratory syndrome coronavirus2) vaccination started there have been multiple reports of different off target adverse effects related to the vaccination, such as myocarditis, immune mediated thrombosis, thrombocytopenia and allergic reactions. W Murphy and Dan Longo in the NEJM November 2021 reported these adverse effects associated with Anti-idiotype antibodies (Ab2) in SARS-CoV-2 vaccination. The pathologic cascade of Ab2 is described in several ways as the antibodies can bind to the protective normal antibodies (Ab1) resulting in immune complex formation and clearance thus impairing Ab1 efficacy. Another action of the Ab2 could be inhibiting normal ligands affecting interaction with angiotensin converting enzyme 2 (ACE2) receptors or stimulating the ACE2 receptor and downregulating the ACE2 function. There is also a description of complementmediated and immune cell attack on ACE2 expressing cells (1). The case reported in this manuscript is related to a severe deterioration in a male with previous diagnose of ME/CFS with worsening lethargy and cognitive skills after SARS-CoV-2 vaccination. The outstanding clinical improvement after starting oral Colchicine is the reason for this paper. Case Report: A 46-year-old male with a previous history of Sarcoidosis and Haemochromatosis had ME/CFS since 2016. He was followed up at Noosa Hospital clinic related to his ME/CFS. His general symptoms related to this condition were under control and he was able to work and study at the University. After the second dose of his SARS-CoV-2 (Pfizer -BioNTech COVID-19) vaccination in August 2021 his general condition deteriorated. During September-October 2021 his cognitive skills declined and he had to stop his university studies. The patient also stopped driving his car because of lethargy and could not do any sport recreational activity. Because of ME/CFS he was on treatment with multivitamins and low dose Naltrexone and Spironolactone before vaccination. After the ME/CFS clinical deterioration the decision was to start Colchicine 0.5 mg a day (November 2021). After four weeks of Colchicine plus his previous medication, his level of energy and cognitive skills recovered to pre vaccination status. Discussion: The immunologic cascade after SARS-CoV-2 vaccination triggered by Ab2 ended in activation of pyrin domain containing protein3 (NRLP3 Inflammasome). This is the pattern of activation for interleukin (IL-1beta). This may determine a general increase in the systemic and microglia inflammation as described in ME/CFS. The clinical manifestation in the present case was worsening in the symptoms of the ME/CFS. The patient was already on Spironolactone targeting the increase on number of macrophages ACE2 receptors as immune modulation. An anti-inflammatory synergy between Colchicine and Spironolactone is currently the focus of research in atherosclerosis. Colchicine has a direct effect on phagocytes leading to inflammasome inhibition and impaired production of IL-1 beta. Conclusion: The Colchicine had a beneficial effect in recovering this patient from an exacerbation of his ME/CFS induced by SARS-CoV-2 vaccination.

16.
Cytokine Growth Factor Rev ; 2022 Jul 06.
Article in English | MEDLINE | ID: covidwho-1914293

ABSTRACT

Considering the high impact that severe Coronavirus disease 2019 (COVID-19) cases still pose on public health and their complex pharmacological management, the search for new therapeutic alternatives is essential. Mesenchymal stromal cells (MSCs) could be promising candidates as they present important immunomodulatory and anti-inflammatory properties that can combat the acute severe respiratory distress syndrome (ARDS) and the cytokine storm occurring in COVID-19, two processes that are mainly driven by an immunological misbalance. In this review, we provide a comprehensive overview of the intricate inflammatory process derived from the immune dysregulation that occurs in COVID-19, discussing the potential that the cytokines and growth factors that constitute the MSC-derived secretome present to treat the disease. Moreover, we revise the latest clinical progress made in the field, discussing the most important findings of the clinical trials conducted to date, which follow 2 different approaches: MSC-based cell therapy or the administration of the secretome by itself, as a cell-free therapy.

17.
Journal of Obstetric, Gynecologic & Neonatal Nursing ; 51(4, Supplement):S1-S2, 2022.
Article in English | ScienceDirect | ID: covidwho-1914707
18.
Viral Immunol ; 35(6): 404-417, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1915522

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. COVID-19 has a broad clinical spectrum from asymptomatic patients to multiorgan dysfunction and septic shock. Most of the common symptoms of COVID-19 are classified as respiratory disorders, but some reports show neurological involvements. During the COVID-19 pandemic, a case series of neurological complications, such as Guillain-Barré syndrome (GBS), were reported. GBS is a neuroimmune disorder with acute inflammatory radicular polyneuropathy in different parts of the peripheral nerve. Some studies have reported GBS as an inflammatory neuropathy related to various viral infections, such as cytomegalovirus (CMV), Epstein-Barr Virus (EBV), herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, and Zika virus. There are some immunomodulation approaches for the management of GBS. Studies have evaluated the effects of the various therapeutic approaches, including intravenous immunoglobulin (IVIG), plasma exchange (PE), complement inhibitors, and corticosteroids to regulate overactivation of immune responses during GBS in experimental and clinical studies. In this regard, the possible association between GBS and SARS-CoV-2 infection during the outbreak of the current pandemic and also the mentioned therapeutic approaches were reviewed.


Subject(s)
COVID-19 , Epstein-Barr Virus Infections , Guillain-Barre Syndrome , Zika Virus Infection , Zika Virus , COVID-19/complications , Epstein-Barr Virus Infections/complications , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/epidemiology , Guillain-Barre Syndrome/therapy , Herpesvirus 4, Human , Humans , Pandemics , SARS-CoV-2
19.
Front Public Health ; 10: 888168, 2022.
Article in English | MEDLINE | ID: covidwho-1911118

ABSTRACT

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and associated development of clinical symptoms of COVID-19 have presented an enormous global impact on our health care systems, public health and economy. To date several observational epidemiological studies consistently found that vitamin D deficiency, measured as low levels of circulating 25-hydroxyvitamin D, is associated with cardiovascular diseases, diabetes, certain cancers, autoimmune diseases and many infectious diseases, including acute respiratory infections. Since vitamin D is not merely immunosuppressive but also acts as an immunomodulator in tolerance and homeostasis, many experts have considered a role of vitamin D in the prevalence and severity of immune mediated inflammatory diseases, such as SARS-CoV-2, adding to the evidence of the importance of vitamin D in the immune response against viral respiratory infections and reinforcing the need for targeted vitamin D supplementation, with a focus on high-risk populations and a high-dose supplementation treatment for COVID-19 hospitalized patients. The expected transition to endemicity of SARS-CoV-2 even further corroborates as a potential of vitamin D as an potential mitigation tool for the prevention of COVID-19. The aim of this paper is to analyse the current evidence regarding vitamin D and present a hypothesis of its potential role in the current COVID-19 pandemic and in the future as a potential preventive measurement in public health.


Subject(s)
COVID-19 , COVID-19/epidemiology , Dietary Supplements , Humans , Pandemics/prevention & control , SARS-CoV-2 , Vitamin D/therapeutic use , Vitamins/therapeutic use
20.
Traditional Medicine Research ; 7(5):9, 2022.
Article in English | Web of Science | ID: covidwho-1897403

ABSTRACT

The whole world has been challenged by the COVID-19, where people with poor immune status became the target. It is high time for us to strengthen our immunity through some safe, efficient and cost-effective immune boosters. Tinospora cordifolia (Thunb.) Miers is a well-known medicinal plant as the whole plant (leaves, stems and roots) is used extensively for different ailments, since it is rich in many bioactive secondary metabolites. The immunomodulatory efficacy of Tinospora cordifolia was reported by several workers and this plant is considered to be a "Rasayana" herb in Ayurveda because of its potential cell renewal, health re-establishment and physical equilibrium maintenance capabilities. 1,4-Linked arabinogalactan polysaccharide (G1-4A), an acidic polysaccharide and arabinogalactan polymer is reported to strengthen host innate immunity by multifactorial pathways. It induces immune cells (neutrophil, macrophage, T lymphocyte) proliferation and increases cytokine/chemokine production and reactive oxygen species generation thereby contributing to boost our immunity. G1-4A activates macrophages by a classical pathway in toll-like receptor 4 - myeloid differentiation primary response 88 dependent manner, natural killer cells and cytotoxic T cells to destroy pathogens, virus-infected cells, or tumor cells. Binding of G1-4A to the toll-like receptor or mannose receptor activates a cascade of events along with nuclear translocation of nuclear factor-kappa B leading to the synthesis of different cytokine/chemokine and reactive oxygen species generation. Natural immunomodulators like G1-4A are safer and cheaper, when extracted from botanical sources. Therefore, such phytocompounds can be taken as a daily supplement to enhance immunity, which might be beneficial to fight and survive in this ongoing pandemic health crisis.

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