Coronavirus disease 2019: investigational therapies in the prevention and treatment of hyperinflammation.
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ABSTRACT:
SUBMITTER: Amigues I
PROVIDER: S-EPMC7879704 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The novel coronavirus disease (COVID-2019) caused by severe acute respiratory syndrome coronavirus (called SARS-CoV-2) emerged in China in December 2019 and then spread rapidly to more than 200 countries around the world, including the United States, Spain, Italy, the United Kingdom, Germany, France, Japan, and South Korea, resulting in more than 208,112 deaths worldwide. As there is no approved vaccine or therapeutic available to control the COVID-2019 pandemic, scientists across the world are trying every possible way to find antivirals specific to this virus. In this urgent situation, parallel to the development of new vaccines and drugs, many previously approved antiviral drugs of broad range such as arbidol, interferon alfa, chloroquine, remdesivir, and favipiravir are presently undergoing clinical trials against COVID-19. So far some positive findings have been obtained, and here we present a thorough overview of all possible antiviral medicines that can control this pandemic of SARS-CoV-2.
| S-EPMC8989131 | biostudies-literature
Project description:ObjectiveThis study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS).MethodsWe retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.ResultsOf 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses.InterpretationThis study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.
| S-EPMC8013440 | biostudies-literature
Project description:The causative agent for coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, appears exceptional in its virulence and immunopathology. In some patients, the resulting hyperinflammation resembles a cytokine release syndrome. Our knowledge of the immunopathogenesis of coronavirus disease 2019 is evolving and anti-cytokine therapies are under active investigation. This narrative review summarizes existing knowledge of the immune response to coronavirus infection and highlights the current and potential future roles of therapeutic strategies to combat the hyperinflammatory response of patients with coronavirus disease 2019.Data sourcesRelevant and up-to-date literature, media reports, and author experiences were included from Medline, national newspapers, and public clinical trial databases.Study selectionThe authors selected studies for inclusion by consensus.Data extractionThe authors reviewed each study and selected approrpriate data for inclusion through consensus.Data synthesisHyperinflammation, reminiscent of cytokine release syndromes such as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, appears to drive outcomes among adults with severe coronavirus disease 2019. Cytokines, particularly interleukin-1 and interleukin-6, appear to contribute importantly to such systemic hyperinflammation. Ongoing clinical trials will determine the efficacy and safety of anti-cytokine therapies in coronavirus disease 2019. In the interim, anti-cytokine therapies may provide a treatment option for adults with severe coronavirus disease 2019 unresponsive to standard critical care management, including ventilation.ConclusionsThis review provides an overview of the current understanding of the immunopathogenesis of coronavirus disease 2019 in adults and proposes treatment considerations for anti-cytokine therapy use in adults with severe disease.
| S-EPMC7419062 | biostudies-literature
Project description:There is a proliferation of clinical trials worldwide to find effective therapies for patients diagnosed with coronavirus disease 2019 (COVID-19). The endpoints that are currently used to evaluate the efficacy of therapeutic agents against COVID-19 are focused on clinical status at a particular day or on time to a specific change of clinical status. To provide a full picture of the clinical course of a patient and make complete use of available data, we consider the trajectory of clinical status over the entire follow-up period. We also show how to combine the evidence of treatment effects on the occurrences of various clinical events. We compare the proposed and existing endpoints through extensive simulation studies. Finally, we provide guidelines on establishing the benefits of treatments.
| S-EPMC7454372 | biostudies-literature
Project description:ImportanceChildren of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required.ObjectiveTo define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment.Design, setting, and participantsPharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population.InterventionsSimulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies.Main outcomes and measuresThe primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration.ResultsFor hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL).Conclusions and relevanceThis analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.
| S-EPMC7275264 | biostudies-literature
Project description:Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues.
2024-04-22 | GSE202553 | GEO
Project description:The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data.
| S-EPMC7163352 | biostudies-literature
Project description:BackgroundThough chest computed tomography (CT) and digital radiography (DR) is important in the diagnosis and treatment of COVID-19, for patients with COVID-19 who may need magnetic resonance imaging (MRI) due to other complications, we proposed the MRI procedures for patients and medical staff to reduce the risk of infection between them.MethodsCombining two cases in our hospital and other literature, a solution about the procedure and necessary preventive and protective measures for MRI examination of COVID-19 patients is proposed for peer reference with the help of experts from our hospital infection-control department. The solution that meets the hospital infection-control regulations covers five aspects including the layout requirements for the MRI room in the radiology department, preparation before admission, preparation of medical staff, preparation of patients, and terminal disinfection after MRI examination. Radiology personnel should strictly abide by the regulations on infection prevention and control. MRI technicians who have been in close contact with COVID-19 patients should receive strict medical observation for two weeks. Each step should be performed carefully to minimize the risk of hospital infection.ResultsA solution that includes five aspects was formulated to prevent the potential contamination during the MRI scan for COVID-19 patients. These five aspects are layout requirements in the MRI room, preparation before admission, preparation of medical staff, preparation of patients, and terminal disinfection after an examination. MRI technicians who have been in close contact with COVID-19 patients should receive strict medical observation for two weeks.ConclusionsTo prevent and control the potential hospital infection during the MRI examination for COVID-19 patients, a solution including five aspects was initially proposed.
| S-EPMC7575983 | biostudies-literature
Project description:Coronavirus Disease 2019 (COVID-19) has become a major health problem causing severe acute respiratory illness in humans. It has spread rapidly around the globe since its first identification in Wuhan, China, in December 2019. The causative virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the World Health Organization (WHO) named the new epidemic disease Coronavirus Disease (COVID-19). The incidence of COVID-19 continues to increase with more than three million confirmed cases and over 244,000 deaths worldwide. There is currently no specific treatment or vaccine against COVID-19. Therefore, in the absence of pharmaceutical interventions, the implementation of precautions and hygienic measures will be essential to control and to minimize human transmission of the virus. In this review, we highlight the epidemiology, transmission, symptoms, and treatment of this disease, as well as future strategies to manage the spread of this fatal coronavirus.
| S-EPMC7352127 | biostudies-literature
Project description:Alzheimer's disease (AD) is the most common cause of dementia associated with a progressive neurodegenerative disorder, with a prevalence of 44 million people throughout the world in 2015, and this figure is estimated to double by 2050. This disease is characterized by blood-brain barrier disruption, oxidative stress, mitochondrial impairment, neuroinflammation, and hypometabolism; it is related to amyloid-β peptide accumulation and tau hyperphosphorylation as well as a decrease in acetylcholine levels and a reduction of cerebral blood flow. Obesity is a major risk factor for AD, because it induces adipokine dysregulation, which consists of the release of the proinflammatory adipokines and decreased anti-inflammatory adipokines, among other processes. The pharmacological treatments for AD can be divided into two categories: symptomatic treatments such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists and etiology-based treatments such as secretase inhibitors, amyloid binders, and tau therapies. Strategies for prevention of AD through nonpharmacological treatments are associated with lifestyle interventions such as exercise, mental challenges, and socialization as well as caloric restriction and a healthy diet. AD is an important health issue on which all people should be informed so that prevention strategies that minimize the risk of its development may be implemented.
| S-EPMC4980501 | biostudies-literature