Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review.
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ABSTRACT: Background
Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19.Methods
This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence.Discussion
The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review.Trial registration
PROSPERO 2020 CRD42020175648.
SUBMITTER: Geisler BP
PROVIDER: S-EPMC8103882 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19.MethodsThis systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence.DiscussionThe challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review.Systematic review registrationPROSPERO 2020 CRD42020175648.
| S-EPMC7265692 | biostudies-literature
Project description:Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.
| S-EPMC7141113 | biostudies-literature
Project description:The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation. Trials (n = 226) were fully assessed for the use of a repurposed drug, identifying a total of 141 therapeutic trials using a repurposed drug to target inflammation in COVID-19 infection. Building on the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial demonstrating the benefit of low dose dexamethasone in COVID-19, repurposed drugs targeting inflammation are promising. Repurposed drugs directed at inflammation in COVID-19 primarily have been drawn from cancer therapies and immunomodulatory therapies, specifically targeted anti-inflammatory, anti-complement, and anti-rejection agents. The proposed mechanisms for many cytokine-directed and anti-rejection drugs are focused on evidence of efficacy in cytokine release syndromes in humans or animal models. Anti-complement-based therapies have the potential to decrease both inflammation and microvascular thrombosis. Cancer therapies are hypothesized to decrease vascular permeability and inflammation. Few publications to date describe using these drugs in COVID-19. Early COVID-19 intervention trials have re-emphasized the subtle, but important cardiotoxic sequelae of potential therapies on outcomes. The volume of trials targeting the COVID-19 hyper-inflammatory phase continues to grow rapidly with the evaluation of repurposed drugs and late-stage investigational agents. Leveraging known clinical safety profiles and pharmacodynamics allows swift investigation in clinical trials for a novel indication. Physicians should remain vigilant for cardiotoxicity, often not fully appreciated in small trials or in short time frames.
| S-EPMC7565788 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 continues to grow and spread throughout the world since being declared a pandemic. Despite extensive scientific research globally including repurposing of several existing drugs, there is no effective or proven therapy for this enigmatic disease which is still largely managed empirically This systematic review evaluated the role of hydroxychloroquine (HCQ) in the treatment of COVID-19 infection and was conducted using Cochrane methodology for systematic reviews of interventional studies including risk of bias assessment and grading of the quality of evidence. Only prospective clinical trials randomly assigning COVID-19 patients to HCQ plus standard of care therapy (test arm) versus placebo/standard of care (control arm) were included. Data were pooled using the random-effects model and expressed as risk ratio (RR) with 95% confidence interval (CI). A total of 10,492 patients from 19 randomised controlled trials were included. The use of HCQ was not associated with higher rates of clinical improvement (RR = 1.00, 95% CI: 0.96-1.03, p = 0.79) or reduction in all-cause mortality by Day14 (RR = 1.07, 95% CI: 0.97-1.19, p = 0.19) or Day28 (RR = 1.08, 95% CI: 0.99-1.19, p = 0.09) compared to placebo/standard of care. There was no significant difference in serious adverse events between the two arms (RR = 1.01, 95% CI: 0.85-1.19, p = 0.95). There is low-to-moderate certainty evidence that HCQ therapy is generally safe but does not reduce mortality or enhance recovery in patients with COVID-19 infection.
| S-EPMC8420202 | biostudies-literature
Project description:Background and purposeVarious neurological findings including stroke in patients with coronavirus disease 2019 (COVID-19) have been described, although no clarity exists regarding the nature and pattern of this association. This systematic review aims to report the characteristics of stroke in patients with COVID-19.MethodsThree authors independently searched Web of Science, Embase, Scopus, and PubMed starting from inception up to May 22, 2020. The data for individual patients was extracted where available from published reports including clinical and laboratory parameters and analysed for any significant associations between variables.ResultsWe identified 30 relevant articles involving 115 patients with acute or subacute stroke with COVID-19. The mean±standard deviation age was 62.5±14.5 years. Stroke was ischemic in majority of the patients (101 [87.8%]). Hypertension (42 [42%]), dyslipidaemia (24 [26.1%]), and diabetes (23 [23.2%]) were the major vascular risk factors. Most of the patients (80 [85.1%]) had COVID-19 symptoms at the time of stroke with a median interval of 10 days to stroke from the diagnosis of COVID-19. Three-fourths (86 [74.8%]) of the patients were critically ill which frequently delayed the diagnosis of stroke. High levels of D-dimer, and ferritin were observed in these patients. Patients with COVID-19 and stroke had a high mortality (47.9%). Factors associated with mortality were intensive care unit admission, having two or more vascular risk factors, particularly smoking and high levels of D-dimer, C-reactive protein, and lactate dehydrogenase.ConclusionsThe association between stroke and COVID-19 is probably multifactorial including an amalgamation of traditional vascular risk factors, proinflammatory and a prothrombotic state. Prospectively collected data is required in the future to confirm this hypothesis.
| S-EPMC7568983 | biostudies-literature
Project description:The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become the current health concern and threat to the entire world. Thus, the world needs the fast recognition of appropriate drugs to restrict the spread of this disease. The global effort started to identify the best drug compounds to treat COVID-19, but going through a series of clinical trials and our lack of information about the details of the virus's performance has slowed down the time to reach this goal. In this work, we try to select the subset of human proteins as candidate sets that can bind to approved drugs. Our method is based on the information on human-virus protein interaction and their effect on the biological processes of the host cells. We also define some informative topological and statistical features for proteins in the protein-protein interaction network. We evaluate our selected sets with two groups of drugs. The first group contains the experimental unapproved treatments for COVID-19, and we show that from 17 drugs in this group, 15 drugs are approved by our selected sets. The second group contains the external clinical trials for COVID-19, and we show that 85% of drugs in this group, target at least one protein of our selected sets. We also study COVID-19 associated protein sets and identify proteins that are essential to disease pathology. For this analysis, we use DAVID tools to show and compare disease-associated genes that are contributed between the COVID-19 comorbidities. Our results for shared genes show significant enrichment for cardiovascular-related, hypertension, diabetes type 2, kidney-related and lung-related diseases. In the last part of this work, we recommend 56 potential effective drugs for further research and investigation for COVID-19 treatment. Materials and implementations are available at: https://github.com/MahnazHabibi/Drug-repurposing.
| S-EPMC8320924 | biostudies-literature
Project description:IntroductionPostoperative nausea and vomiting (PONV) affect approximately 80% of surgical patients and is associated with increased length of hospital stay and systemic costs. Preoperative and postoperative pain, anxiety and depression are also commonly reported. Recent evidence regarding their safety and effectiveness has not been synthesised. The aim of this systematic review is to evaluate the efficacy and safety of herbal medications for the treatment and prevention of anxiety, depression, pain and PONV in patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgical procedures.Methods and analysisThe following electronic databases will be searched up to 1 October 2016 without language or publication status restrictions: CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgeries and managed with herbal medication versus a control group (placebo, no intervention or active control) prophylactically or therapeutically will be considered eligible. Outcomes of interest will include the following: anxiety, depression, pain, nausea and vomiting. A team of reviewers will complete title and abstract screening and full-text screening for identified hits independently and in duplicate. Data extraction, risk of bias assessments and evaluation of the overall quality of evidence for each relevant outcome reported will be conducted independently and in duplicate using the Grading of Recommendations Assessment Development and Evaluation classification system. Dichotomous data will be summarised as risk ratios; continuous data will be summarised as standard average differences with 95% CIs.Ethics and disseminationThis is one of the first efforts to systematically summarise existing evidence evaluating the use of herbal medications in laparoscopic, obstetrical/gynaecological and cardiovascular surgical patients. The findings of this review will be disseminated through peer-reviewed publications and conference presentations.Systematic review registrationPROSPERO CRD42016042838.
| S-EPMC5642794 | biostudies-literature
Project description:BackgroundIn December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic.ObjectiveTo clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options.MethodsWe conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident.ResultsWe were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy.ConclusionsNeurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain-Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.
| S-EPMC7304377 | biostudies-literature
Project description: Not available
| S-EPMC8328127 | biostudies-literature
Project description:BACKGROUND:Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS:A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS:The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 ?mol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 ?mol/L. The viral RNA yield in cells treated with 10 ?mol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48?±?0.02]?×?10vs. 1.00?±?0.12, t?=?150.38, P?<?0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 ?mol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46?±?0.12, vs.1.00?±?0.37, t?=?2.42, P?<?0.05) and viral replication ([6.18?±?0.95]?×?10vs. 1.00?±?0.43, t?=?3.98, P?<?0.05). CONCLUSIONS:Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
| S-EPMC7147283 | biostudies-literature