Description and Analysis of Cytokine Storm in Registered COVID-19 Clinical Trials: A Systematic Review.
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ABSTRACT:
SUBMITTER: Eljaaly K
PROVIDER: S-EPMC8229812 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSince the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics.MethodsThis study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias.ResultsA total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low.ConclusionsIntensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.
| S-EPMC7338108 | biostudies-literature
Project description:ObjectivesDue to the rapid spread of COVID-19 worldwide, many countries have designed clinical trials to find efficient treatments. We aimed to critically report the characteristics of all the registered and published randomized clinical trials (RCTs) conducted on COVID-19, and summarize the evaluation of potential therapies developed in various regions.Evidence acquisitionWe comprehensively searched PubMed, Cochrane Library, Web of Science, Scopus, and Clinicaltrial.gov databases to retrieve all the relevant studies up to July 19, 2021, in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. We included all English-language published/registered RCTs on COVID-19, and excluded non-RCT, in-vitro/in-vivo, editorials, and review studies. Two reviewers independently evaluated all the records, and then analyzed by using SPSS 17.ResultsWithin 3018 included studies, 2801 (92.8%) and 217 (7.2%) were registered or published RCTs consisting of about 600 synthetic drugs. Herbal medicines have been studied in 23 trials (10.6%) among the published RCTs and in 357 registered RCTs (12.7%). Hydroxychloroquine 23 (10.6%) and convalescent plasma 194 (6.9%) alone or in combination with other agents were the most frequently used interventions in published and registered RCTs, respectively. Most published RCTs have been conducted in Western Pacific Region (WPRO) (50 trials, 23.0%) including 45 trials from China. Also, a greater proportion of registered RCTs have been conducted in the Region of the Americas (PAHO) (885 trials, 31.6%) including 596 RCTs from the United States (U.S). Globally, 283 registered trials have been conducted to assess new developed vaccines for COVID or previously established for other disorders.ConclusionThe present study highlighted the wide range of potential therapeutic agents in published and registered COVID-19 clinical trials across a wide range of regions. However, it is urgently required to global coordination in order to conduct more well-designed trials and progress in discovering safe and effective treatments.
| S-EPMC8581284 | biostudies-literature
Project description:BackgroundIn March 2020, the World Health Organization declared the coronavirus disease 2019 as a global pandemic. Though antiviral drugs and antimalarial drugs are considered treatment options for treating coronavirus disease 2019 (COVID-19), no specific antivirals are currently available for its treatment. Efficient use of drug discovery approaches including repurposing or repositioning of drugs used in the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) is considered recently. The widespread application of corticosteroid therapy in COVID-19 should be backed with careful documented pragmatic research of its use in this context.Main bodyThis article aims to analyze various trials registered across the globe providing an overall picture of the use of corticosteroids in the treatment of COVID-19. An extensive search was conducted on the clinical trial registries around the world to identify all the trials reporting information regarding the use of corticosteroids in COVID-19. Our initial search returned 231 trials, out of which 60 trials were finally included in the analysis. Fifty-six studies were interventional trials, and all the trials had clearly defined primary and secondary outcomes of interest, of which only 11 trials had evaluation of respiratory rate as one of their outcomes.ConclusionFew preliminary trial findings show promising results and recommend the use of methylprednisolone and dexamethasone in the severe form of the disease; however, there is insufficient data to prove its benefits over its risks. Routine use of corticosteroids should be favored only after a better insight is obtained, with the completion of these trials.
| S-EPMC7968560 | biostudies-literature
Project description:IntroductionThe coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine storm, contributing to ARDS, multiple-organ failure and, in the most severe cases, death. We aimed to quantify the differences in the circulating levels of major inflammatory and immunological markers between severe and nonsevere COVID-19 patients.MethodsRelevant studies were identified from PubMed, EMBASE, Web of Science, SCOPUS and preprint servers. Risk of bias was assessed for each study, using appropriate checklists. All studies were described qualitatively and a subset was included in the meta-analysis, using forest plots.ResultsBased on 23 studies, mean cytokine levels were significantly higher (IL-6: MD, 19.55 pg/mL; CI, 14.80, 24.30; IL-8: MD, 19.18 pg/mL; CI, 2.94, 35.43; IL-10: MD, 3.66 pg/mL; CI, 2.41, 4.92; IL-2R: MD, 521.36 U/mL; CI, 87.15, 955.57; and TNF-alpha: MD, 1.11 pg/mL; CI, 0.07, 2.15) and T-lymphocyte levels were significantly lower (CD4+ T cells: MD, -165.28 cells/µL; CI, -207.58, -122.97; CD8+ T cells: MD, -106.51 cells/µL; CI, -128.59, -84.43) among severe cases as compared to nonsevere ones. There was heterogeneity across studies due to small sample sizes and nonuniformity in outcome assessment and varied definitions of disease severity. The overall quality of studies was sub-optimal.ConclusionSevere COVID-19 is characterized by significantly increased levels of pro-inflammatory cytokines and reduced T lymphocytes. Well-designed and adequately powered prospective studies are needed to amplify the current evidence and provide definitive answers to dilemmas regarding timing and type of anti-COVID-19 therapy particularly in severe patients.
| S-EPMC7646004 | biostudies-literature
Project description: Not available
| S-EPMC7472975 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first reported in December 2019 in Wuhan, China, but now more than 200 countries have been affected and the coronavirus pandemic is still ongoing. The severity of COVID-19 symptoms can range from mild to severe. FDA approved remdesivir as a treatment of COVID-19 so far. Various clinical trials are underway to find an effective method to treat patients with COVID-19. This review aimed at summarizing 219 registered clinical trials in the ClinicalTrials.gov database with possible mechanisms, and novel findings of them, and other recent publications related to COVID-19. According to our analyses, various treatment approaches and drugs are being investigated to find an effective drug to cure COVID-19 and among all strategies, three important mechanisms are suggested to be important against COVID-19 including antiviral, anti-inflammatory, and immunomodulatory properties. Our review can help future studies get on the way to finding an effective drug for COVID-19 treatment by providing ideas for similar researches.
| S-EPMC7753306 | biostudies-literature
Project description:Highlights • Clinical picture generally manifests as “overlap syndrome” and leads to vicious circle.• Early identification of rising cytokine storm and multilevel course of treatment is imperative.• Adjunctive treatment improves the success in fight with consequences of CRS.• Recognition of epigenetic factors might lead to personalized approach. Cytokine storm is a form of uncontrolled systemic inflammatory reaction activated by a variety of factors and leading to a harmful homeostatic process, even to patient´s death. Triggers that start the reaction are infection, systemic diseases and rarely anaphylaxis. Cytokine storm is frequently mentioned in connection to medical interventions such as transplantation or administration of drugs. Presented mini-review would like to show current possibilities how to fight or even stop such a life-threatening, immune-mediated process in order to save lives, not only in COVID-19 patients. Early identification of rising state and multilevel course of treatment is imperative. The most widely used molecule for systemic treatment remains tocilizumab. Except for anti-IL-6 treatment, contemporary research opens the possibilities for combination of pharmaceutical, non-pharmaceutical and adjunctive treatment in a successful fight with consequences of cytokine storm. Further work is needed to discover the exact signaling pathways that lead to cytokine storm and to determine how these effector molecules and/or combination of processes can help to resolve this frequently fatal episode of in?ammation. It is a huge need for all scientists and clinicians to establish a physiological rational for new therapeutic targets that might lead to more personalized medicine approaches.
| S-EPMC7524442 | biostudies-literature
Project description:BackgroundPost-acute COVID-19 syndrome (PACS) is a well-recognized, complex, systemic disease which is associated with substantial morbidity. There is a paucity of established interventions for the treatment of patients with this syndrome.ObjectivesTo systematically review registered trials currently investigating therapeutic modalities for PACS.Data sourcesA search was conducted up to the 16 September, 2022, using the COVID-19 section of the WHO Internal Clinical Trials Registry Platform.Study eligibility criteria, participants, and interventionsInterventional clinical trials of any sample size examining any therapeutic modality targeting persistent symptoms among individuals after diagnosis with COVID-19.MethodsData on trial characteristics and intervention characteristics were collected and summarized.ResultsAfter screening 17 125 trials, 388 trials, from 42 countries, were eligible. In total, we had 406 interventions, of which 368 were mono-therapeutic strategies, whereas 38 were intervention combinations. Among 824 primary outcomes identified, there were >300 different outcomes. Rehabilitation was the most employed class of intervention in 169 trials. We encountered 76 trials examining the pharmacological agents of various classes, with the most common agent being colchicine. Complementary and alternative medicine encompassed 64 trials exploring traditional Chinese medicine, Ayurveda, homeopathic medications, naturopathic medications, vitamins, dietary supplements, and botanicals. Psychotherapeutic and educational interventions were also employed in 12 and 4 trials, respectively. Other interventions, including transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, general electrical stimulation, cranial electrotherapy stimulation, various stem cell interventions, and oxygen therapy interventions, were also employed.ConclusionWe identified 388 registered trials, with a high degree of heterogeneity, exploring 144 unique mono-therapeutic interventions for PACS. Most studies target general alleviation of symptoms. There is a need for further high-quality and methodologically robust PACS treatment trials to be conducted with standardization of outcomes while following WHO's recommendation for uniform evaluation and treatment.
| S-EPMC9837206 | biostudies-literature
Project description:Acute cardiac injuries occur in 20%–25% of hospitalized COVID‐19 patients. Herein, we demonstrate that human cardiac organoids (hCOs) are a viable platform to model the cardiac injuries caused by COVID‐19 hyperinflammation. As IL‐1β is an upstream cytokine and a core COVID‐19 signature cytokine, it was used to stimulate hCOs to induce the release of a milieu of proinflammatory cytokines that mirror the profile of COVID‐19 cytokine storm. The IL‐1β treated hCOs recapitulated transcriptomic, structural, and functional signatures of COVID‐19 hearts. The comparison of IL‐1β treated hCOs with cardiac tissue from COVID‐19 autopsies illustrated the critical roles of hyper‐inflammation in COVID‐19 cardiac insults and indicated the cardioprotective effects of endothelium. The IL‐1β treated hCOs thus provide a defined and robust model to assess the efficacy and potential side effects of immunomodulatory drugs, as well as the reversibility of COVID‐19 cardiac in- juries at baseline and simulated exercise conditions.
2023-12-20 | GSE250520 | GEO
Project description:Severe COVID-19 may progress into acute respiratory distress syndrome (ARDS) with high mortality risk. Its exact pathological mechanism, therapeutic obstacles and the clinical sequelae are critical and unresolved issues. Here, we reported a representative COVID-19 induced ARDS case experienced initially stable, then suddenly deteriorating up to final respiratory failure courses, until his death despite of lung transplantation. His lung pathology showed necrosis of parenchymal tissues, extensive immune cell infiltration and lung fibrosis. Single-cell RNA sequencing revealed various immune cell populations were largely expanded in his lung, and manifested inflammatory/activated functions. We also showed that cell-crosstalk between lung macrophages and fibroblasts promoted pulmonary fibrosis through IL-1B and TGF-Β signaling pathways. Although SARS-CoV-2 RNA remained undetectable in his respiratory tract specimens including BALF at the later stage of his disease, the presence of SARS-CoV-2 was definitely confirmed in his lung tissues. Thus, this case indicates the pathological mechanism of severe COVID-19 includes pulmonary SARS-CoV-2 persistence, deranged inflammation and the extensive lung fibrosis which set the barriers for effective treatments and indicate potential health complications for severe COVID-19 patients.
2020-12-01 | GSE149878 | GEO