scholarly journals A practical approach for the compassionate use of convalescent plasma in patients with severe COVID-19 in developing countries

2020 ◽  
Vol 14 (07) ◽  
pp. 737-741
Author(s):  
Brenner Elías Sabando Vélez ◽  
Carlos Plaza Meneses ◽  
Miguel Felix ◽  
Emanuel Vanegas ◽  
Valeria L Mata ◽  
...  
Keyword(s):  
Developing Countries ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Case Series ◽  
Public Health Problem ◽  
Practical Approach ◽  
Current Evidence ◽  
Global Public Health ◽  
Compassionate Use

The COVID-19 pandemic has affected 187 countries, representing a global public health problem. The increasing number of critically ill patients and deaths have fueled a desperate search for treatments that can halt the course of the disease. Currently, there are several experimental therapies with demonstrated in vitro activity against COVID-19 used in clinical practice, including hydroxychloroquine, remdesivir, interleukin-6 pathway inhibitors, and convalescent plasma; however, to date no agent has proven efficacy against COVID-19. In the case of convalescent plasma, this therapy consists in obtaining neutralizing antibodies from previously infected individuals by plasmapheresis and administering them to patients with severe disease. Recently, the use of convalescent plasma has shown promising results in preliminary studies, with case series reporting a decrease in temperature, and viral load, as well as improvement in clinical parameters among patients receiving this treatment. However, there are still unmet needs regarding the safety profile, tolerability, dosage, and timing this therapy should be given. Based on this, the objective of our study was to develop and propose a practical approach for the compassionate use of convalescent plasma for the treatment of patients with severe COVID-19, given the constrains and limitations of developing countries. We encourage health professionals in developing countries to use the current evidence and approaches to experimental treatments for patients with COVID-19, adapting them to their conditions, and always based on a thorough risk-benefit evaluation for each patient, and whenever possible to design and promote the much needed research in this field.

scholarly journals Neutralizing Antibody Therapeutics for COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 628
Author(s):  
Aeron C. Hurt ◽  
Adam K. Wheatley
Keyword(s):  
High Risk ◽  
Neutralizing Antibodies ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Supplemental Oxygen ◽  
European Medicines Agency ◽  
Global Public Health ◽  
Public Health Burden

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.

scholarly journals Clinical management of Lupus patients during the COVID-19 pandemic

Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1661-1672
Author(s):  
Alice Mason ◽  
Emily Rose ◽  
Christopher J Edwards
Keyword(s):  
Kinase Inhibitors ◽  
Viral Infections ◽  
Positive Impact ◽  
Severe Disease ◽  
Social Contact ◽  
Janus Kinase ◽  
Current Evidence ◽  
Janus Kinase Inhibitors ◽  
Huge Impact

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Historical evidence suggests that Lupus patients have a higher incidence of several viral infections. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities. In this context there has been concern that Lupus patients may be at a higher risk of developing COVID-19 and suffering a severe disease course. As a result, many Lupus patients have been advised to ‘shield’ by isolating from social contact in the hope that this will reduce the likelihood of infection. Early clinical data does not appear to show that the incidence of COVID-19 is higher in Lupus patients. Reassuringly, the clinical course of COVID-19 in Lupus does not generally seem to be more severe than in the general population. There has been huge interest in repurposing existing drugs as potential treatments, including several used to treat Lupus. Of these, corticosteroids and hydroxychloroquine are the most well researched so far. The current evidence suggests that the corticosteroid dexamethasone improves outcome for the sickest COVID-19 patients requiring respiratory support. Initial reports suggested that hydroxychloroquine could have a positive impact on the course of COVID-19, however larger prospective studies have not supported this. Janus kinase inhibitors, currently being investigated for efficacy in lupus, have been shown to have anti-viral effects in vitro and inhibiting the JAK-STAT pathway may dampen down the host hyper-inflammatory response. Several trials are ongoing to assess the outcome of the use of JAK inhibitors in COVID-19 positive patients. For most patients continuing with their existing therapies to prevent a lupus flare or adverse events associated with sudden corticosteroid withdrawal is important whilst an Individualised risk assessment remains vital.

scholarly journals Animal Models as Tools to Investigate Antidiabetic and Anti-Inflammatory Plants

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mohamed Eddouks ◽  
Debprasad Chattopadhyay ◽  
Naoufel Ali Zeggwagh
Keyword(s):  
Animal Models ◽  
Public Health Problem ◽  
New Drugs ◽  
Inflammatory Activity ◽  
Global Public Health ◽  
Plant Materials ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory ◽  
Materials Used

Plants have been historically used for diabetes treatment and related anti-inflammatory activity throughout the world; few of them have been validated by scientific criteria. Recently, a large diversity of animal models has been developed for better understanding the pathogenesis of diabetes mellitus and its underlying inflammatory mechanism and new drugs have been introduced in the market to treat this disease. The aim of this work is to review the available animal models of diabetes and anti-inflammatory activity along with somein vitromodels which have been used as tools to investigate the mechanism of action of drugs with potential antidiabetic properties and related anti-inflammatory mechanism. At present, the rigorous procedures for evaluation of conventional antidiabetic medicines have rarely been applied to test raw plant materials used as traditional treatments for diabetes; and natural products, mainly derived from plants, have been tested in chemically induced diabetes model. This paper contributes to design new strategies for the development of novel antidiabetic drugs and its related inflammatory activity in order to treat this serious condition which represents a global public health problem.

scholarly journals The role of cGMP and its signaling pathways in kidney disease

2016 ◽  
Vol 311 (4) ◽  
pp. F671-F681 ◽  
Author(s):  
Kunyu Shen ◽  
David W. Johnson ◽  
Glenda C. Gobe
Keyword(s):  
Kidney Disease ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Second Messengers ◽  
Public Health Problem ◽  
Research Field ◽  
Current Evidence ◽  
Global Public Health ◽  
Kidney Fibrosis ◽  
Downstream Signaling

Cyclic nucleotide signal transduction pathways are an emerging research field in kidney disease. Activated cell surface receptors transduce their signals via intracellular second messengers such as cAMP and cGMP. There is increasing evidence that regulation of the cGMP-cGMP-dependent protein kinase 1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway may be renoprotective. Selective PDE5 inhibitors have shown potential in treating kidney fibrosis in patients with chronic kidney disease (CKD), via their downstream signaling, and these inhibitors also have known activity as antithrombotic and anticancer agents. This review gives an outline of the cGMP-cGK1-PDE signaling pathways and details the downstream signaling and regulatory functions that are modulated by cGK1 and PDE inhibitors with regard to antifibrotic, antithrombotic, and antitumor activity. Current evidence that supports the renoprotective effects of regulating cGMP-cGK1-PDE signaling is also summarized. Finally, the effects of icariin, a natural plant extract with PDE5 inhibitory function, are discussed. We conclude that regulation of cGMP-cGK1-PDE signaling might provide novel, therapeutic strategies for the worsening global public health problem of CKD.

Suicide in Developing Countries (1)

Crisis ◽  
2005 ◽  
Vol 26 (3) ◽  
pp. 104-111 ◽  
Author(s):  
Lakshmi Vijayakumar ◽  
K. Nagaraj ◽  
Jane Pirkis ◽  
Harvey Whiteford
Keyword(s):  
Developing Countries ◽  
Public Health Problem ◽  
Data Availability ◽  
World Health ◽  
Global Public Health ◽  
Socioeconomic Indicators ◽  
Suicide Rates ◽  
Country Level ◽  
Education Levels ◽  
Health Organization

Abstract. Objective. Suicide is a global public health problem, but relatively little epidemiological investigation of the phenomenon has occurred in developing countries. This paper aims to (1) examine the availability of rate data in developing countries, (2) provide a description of the frequency and distribution of suicide in those countries for which data are available, and (3) explore the relationship between country-level socioeconomic factors and suicide rates. It is accompanied by two companion papers that consider risk factors and preventive efforts associated with suicide in developing countries, respectively. Method. Using World Health Organization data, we calculated the average annual male, female, and total suicide rates during the 1990s for individual countries and regions (classified according to the Human Development Index [HDI]), and examined the association between a range of socioeconomic indicators and suicide rates. Results. For reasons of data availability, we concentrated on medium HDI countries. Suicide rates in these countries were variable. They were generally comparable with those in high HDI countries from the same region, with some exceptions. High education levels, high telephone density, and high per capita levels of cigarette consumption were associated with high suicide rates; high levels of inequality were associated with low suicide rates. Conclusion. Epidemiological investigations of this kind have the potential to inform suicide prevention efforts in developing countries, and should be encouraged.

scholarly journals The unanswered Questions in Hyperuricemia: is it a cause of chronic kidney disease, a compensation mechanism, a coincidence, a consequence of disease or concurrent phenomenon?

2018 ◽  
pp. 48-61
Author(s):  
M. Kolesnyk
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Public Health Problem ◽  
Premature Death ◽  
Current Evidence ◽  
Global Public Health ◽  
High Prevalence ◽  
Therapy Effectiveness ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) has become a global public health problem because of its high prevalence and the accompanying increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. The role of uric acid (UA) in the pathogenesis and progression of CKD remains controversial. Although many evidence-based studies have suggested that UA itself may harm patients with CKD by increasing inflammation and CKD progression, the issue is still a matter of discussions. In this review we try to clarify what is hyperuricemia – cause of CKD, compensation, coincidence, consequence of CKD or it is only an epiphenomenon, and to evaluate current evidence of different types of targeted hypouricemic therapy effectiveness. So, to treat or not to treat?

scholarly journals Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike

2020 ◽  
Author(s):  
Lihong Liu ◽  
Pengfei Wang ◽  
Manoj S. Nair ◽  
Jian Yu ◽  
Micah Rapp ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Global Economy ◽  
Epitope Mapping ◽  
Severe Disease ◽  
Clinical Development ◽  
Receptor Binding Domain ◽  
Cryo Electron Microscopy ◽  
Novel Coronavirus

AbstractThe SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, “all RBD-down” conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

scholarly journals MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

2017 ◽  
Vol 43 (4) ◽  
pp. 1663-1672 ◽  
Author(s):  
Lian Tang ◽  
Yiran Yin ◽  
Juncai Liu ◽  
Zhong Li ◽  
Xiaobo Lu
Keyword(s):  
Bone Marrow ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Public Health Problem ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Global Public Health ◽  
Ovariectomized Mice

Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.

scholarly journals Gender-Related Barriers and Delays in Accessing Tuberculosis Diagnostic and Treatment Services: A Systematic Review of Qualitative Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Lakshmi Krishnan ◽  
Tokunbo Akande ◽  
Anita V. Shankar ◽  
Katherine N. McIntire ◽  
Celine R. Gounder ◽  
...  
Keyword(s):  
Developing Countries ◽  
Physical Dependence ◽  
Public Health Problem ◽  
Qualitative Studies ◽  
System Level ◽  
Service Access ◽  
Global Public Health ◽  
Coding System ◽  
Treatment Services ◽  
Variable Nature

Background. Tuberculosis (TB) remains a significant global public health problem with known gender-related (male versus female) disparities. We reviewed the qualitative evidence (written/spoken narrative) for gender-related differences limiting TB service access from symptom onset to treatment initiation.Methods. Following a systematic process, we searched 12 electronic databases, included qualitative studies that assessed gender differences in accessing TB diagnostic and treatment services, abstracted data, and assessed study validity. Using a modified “inductive coding” system, we synthesized emergent themes within defined barriers and delays limiting access at the individual and provider/system levels and examined gender-related differences.Results. Among 13,448 studies, 28 studies were included. All were conducted in developing countries and assessed individual-level barriers; 11 (39%) assessed provider/system-level barriers, 18 (64%) surveyed persons with suspected or diagnosed TB, and 7 (25%) exclusively surveyed randomly sampled community members or health care workers. Each barrier affected both genders but had gender-variable nature and impact reflecting sociodemographic themes. Women experienced financial and physical dependence, lower general literacy, and household stigma, whereas men faced work-related financial and physical barriers and community-based stigma.Conclusions. In developing countries, barriers limiting access to TB care have context-specific gender-related differences that can inform integrated interventions to optimize TB services.

scholarly journals Live Attenuated Shigella dysenteriae Type 1 Vaccine Strains Overexpressing Shiga Toxin B Subunit

2011 ◽  
Vol 79 (12) ◽  
pp. 4912-4922 ◽  
Author(s):  
Tao Wu ◽  
Christen Grassel ◽  
Myron M. Levine ◽  
Eileen M. Barry
Keyword(s):  
Shiga Toxin ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Shigella Dysenteriae ◽  
Gene Encoding ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Serotype 1 ◽  
Clinical Illness

ABSTRACTShigella dysenteriaeserotype 1 (S. dysenteriae1) is unique among theShigellaspecies and serotypes in the expression of Shiga toxin which contributes to more severe disease sequelae and the ability to cause explosive outbreaks and pandemics.S. dysenteriae1 shares characteristics with otherShigellaspecies, including the capability of causing clinical illness with a very low inoculum (10 to 100 CFU) and resistance to multiple antibiotics, underscoring the need for efficacious vaccines and therapeutics. Following the demonstration of the successful attenuating capacity of deletion mutations in theguaBAoperon inS. flexneri2a vaccine strains in clinical studies, we developed a series ofS. dysenteriae1 vaccine candidates containing the fundamental attenuating mutation inguaBA.All strains are devoid of Shiga toxin activity by specific deletion of the gene encoding the StxA subunit, which encodes enzymatic activity. The StxB subunit was overexpressed in several derivatives by either plasmid-based constructs or chromosomal manipulation to include a strong promoter. All strains are attenuated for growthin vitroin the HeLa cell assay and for plaque formation and were safe in the Serény test and immunogenic in the guinea pigs. Each strain induced robust serum and mucosal anti-S. dysenteriae1 lipopolysaccharide (LPS) responses and protected against wild-type challenge. Two strains engineered to overexpress StxB induced high titers of Shiga toxin neutralizing antibodies. These candidates demonstrate the potential for a live attenuated vaccine to protect against disease caused byS. dysenteriae1 and potentially to protect against the toxic effects of other Shiga toxin 1-expressing pathogens.

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