Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis.
Ontology highlight
ABSTRACT: Background
To better inform clinical practice, we summarized the findings from randomized controlled trials (RCTs) of antivirals for COVID-19.Methods
We systematically searched for literature up to September 2020, and included English-language publications of RCTs among hospitalized COVID-19 patients. We conducted network meta-analysis combining results of both the direct and indirect comparisons of interventions. The efficacy outcomes were clinical progression, all-cause mortality, and viral clearance, and safety outcomes were diarrhea, nausea, and vomiting. We generated treatment rankings (best to worst) and summarized rank probabilities using rankogram.Results
We included 15 RCTs (14,418 patients) from 7,237 retrieved citations. There was no evidence for efficacy of the assessed antivirals compared with placebo/no treatment or with another antiviral for all efficacy outcomes. Lopinavir (400 mg)/ritonavir (100 mg) significantly increased diarrhea, nausea, and vomiting compared with placebo/no treatment and other antivirals, and was ranked worst for these outcomes, while triazavirin (250 mg), baloxavir marboxil (80 mg), and remdesivir (100 mg - 10 days) ranked best, respectively.Conclusions and relevance
The available evidence does not support the use of any antiviral drugs for COVID-19. Cautious interpretations of the findings are, however, advised considering the paucity of the evidence. More RCTs are needed for a stronger evidence base.
SUBMITTER: Okoli GN
PROVIDER: S-EPMC8477589 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Objective:Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Methods:Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. Results:There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference - 361.06 μL [- 439.18, - 282.95], p < 0.001; I 2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference - 395.35 μL [- 165.64, - 625.07], p < 0.001; I 2 87%), experienced ARDS (mean difference - 377.56 μL [- 271.89, - 483.22], p < 0.001; I 2 0%), received ICU care (mean difference - 376.53 μL [- 682.84, - 70.22], p = 0.02; I 2 89%), and have severe COVID-19 (mean difference - 353.34 μL [- 250.94, - 455.73], p < 0.001; I 2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I 2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). Conclusion:This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.
| S-EPMC7245646 | biostudies-literature
Project description:Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to understanding the neurologic characteristic of the disease and help physicians with early diagnosis and management. Objective: To conduct a systematic review and meta-analysis on the neurologic characteristics in patients with COVID-19. Evidence Review: Authors conducted a literature search through PubMed from January 1st, 2020 to April 8th, 2020. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of COVID-19 patients in their data were included. Case reports and case series were also included in this review. The quality of the studies was assessed based on the Oxford Center for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and the heterogeneity test. Finding: From 280 identified studies, 33 were eligible, with 7,559 participants included. Most of the included studies were from China (29 [88%]). Muscle injury or myalgia was the most common (19.2%, 95%CI 15.4-23.2%) neurologic symptom of COVID-19, followed by headache (10.9%, 95%CI 8.62-13.51%); dizziness (8.7%, 95%CI 5.02-13.43%); nausea with or without vomiting (4.6%, 95%CI 3.17-6.27%); concurrent cerebrovascular disease (4.4%, 95%CI 1.92-7.91%); and impaired consciousness (3.8%, 95%CI 0.16-12.04%). Underlying cerebrovascular disease was found in 8.5% (95%CI 4.5-13.5%) of the studies. Conclusion: Neurologic findings vary from non-specific to specific symptoms in COVID-19 patients. Some severe symptoms or diseases can present in the later stage of the disease. Physicians should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients.
| S-EPMC7273516 | biostudies-literature
Project description:ObjectiveThe coronavirus disease 2019 (COVID-19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID-19.MethodsStudies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta-analysis was performed to compare the ferritin level between different patient groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation.ResultsA total of 52 records involving 10 614 COVID-19-confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta-analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non-severe patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation.ConclusionsFerritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.
| S-EPMC7595919 | biostudies-literature
Project description:To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.
| S-EPMC7436402 | biostudies-literature
Project description:PurposeThis study was performed to determine the occurrence of ocular surface manifestations in patients diagnosed with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsA systematic search of electronic databases i.e. PubMed, Web of Science, CINAHL, OVID and Google scholar was performed using a comprehensive search strategy. The searches were current through 31st May 2020. Pooled data from cross-sectional studies was used for meta-analysis and a narrative synthesis was conducted for studies where a meta-analysis was not feasible.ResultsA total of 16 studies reporting 2347 confirmed COVID-19 cases were included. Pooled data showed that 11.64% of COVID-19 patients had ocular surface manifestations. Ocular pain (31.2%), discharge (19.2%), redness (10.8%), and follicular conjunctivitis (7.7%) were the main features. 6.9% patients with ocular manifestations had severe pneumonia. Viral RNA was detected from the ocular specimens in 3.5% patients.ConclusionThe most common reported ocular presentations of COVID-19 included ocular pain, redness, discharge, and follicular conjunctivitis. A small proportion of patients had viral RNA in their conjunctival/tear samples. The available studies show significant publication bias and heterogeneity. Prospective studies with methodical collection and data reporting are needed for evaluation of ocular involvement in COVID-19.
| S-EPMC7643964 | biostudies-literature
Project description:We performed a meta-analysis to determine safety and efficacy of tocilizumab in persons with coronavirus disease-2019 (COVID-19). We searched PubMed, Web of Science and Medline using Boolean operators for studies with the terms coronavirus OR COVID-19 OR 2019-nCoV OR SARS-CoV-2 AND tocilizumab. Review Manager 5.4 was used to analyze data and the modified Newcastle-Ottawa and Jadad scales for quality assessment. We identified 32 studies in 11,487 subjects including three randomized trials and 29 cohort studies with a comparator cohort, including historical controls (N = 5), a matched cohort (N = 12), or concurrent controls (N = 12). Overall, tocilizumab decreased risk of death (Relative Risk [RR] = 0.74; 95% confidence interval [CI], 0.59, 0.93; P = 0.008; I2 = 80%) but not of surrogate endpoints including ICU admission (RR = 1.40 [0.64,3.06]; P = 0.4; I2 = 88%), invasive mechanical ventilation (RR = 0.83 [0.57,1.22]; P = 0.34; I2 = 65%) or secondary infections (RR = 1.30 [0.97,1.74]; P = 0.08; I2 = 65%) and increased interval of hospitalization of subjects discharged alive(mean difference [MD] = 2 days [<1, 4 days]; P = 0.006; I2 = 0). RRs of death in studies with historical controls (RR = 0.28 [0.16,0.49; P < 0.001]; I2 = 62%) or a matched cohort (RR = 0.68 [0.53, 0.87]; P = 0.002; I2 = 42%) were decreased. In contrast, RRs of death in studies with a concurrent control (RR = 1.10 [0.77, 1.56]; P = 0.60; I2 = 85%) or randomized (RR = 1.18 [0.57,2.44]; P = 0.66; I2 = 0) were not decreased. A reduced risk of death was not confirmed in our analyses which questions safety and efficacy of tocilizumab in persons with COVID-19.
| S-EPMC8127467 | biostudies-literature
Project description:BackgroundIntegration of Chinese medical drugs (CMD) and western medicine (WM) has been widely used in the treatment of Coronavirus Disease 2019 (COVID-19). This systematic review aimed to evaluate the efficacy and safety of CMD for COVID-19.MethodA literature search was performed in six databases from injection to June 2020. Both randomized controlled trials (RCTs) and quasi-RCTs were considered as eligible. The quality of included RCTs were assessed by Cochrane Risk of Bias Tool, and Review Manager 5.3 software was used to do meta-analysis.ResultEleven studies with 1259 patients were included in this study. CMD included herbal decoction and Chinese patent medicine. The methodological quality was evaluated as generally unclear. The results of meta-analysis showed that the integration of CMD and WM had better efficacy than WM in number of patients turned to severe and critical type (RR = 0.47, 95% CI=[0.32, 0.69], P < 0.0001), length of hospital stay (MD= -7.95, 95% CI=[-14.66, -1.24], P = 0.02), defervescence time (MD= -1.20, 95% CI=[-2.03, -0.38], P = 0.004), cough resolution rate (RR = 1.37, 95% CI=[1.15, 1.64], P = 0.0004), fatigue resolution rate (RR = 1.37, 95% CI=[1.02, 1.83], P = 0.04), and tachypnea resolution rate (RR = 2.20, 95% CI=[1.11, 4.39], P = 0.02). As for safety, there was no significant difference between two groups.ConclusionCMD may bring potential benefit to patients suffered from COVID-19. However, the quality of included trials is not good enough. High quality study with core outcome set are still required.
| S-EPMC7385501 | biostudies-literature
Project description:BackgroundRandomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear.MethodsWe searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsWe identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir-ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir-ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty).InterpretationMolnupiravir and nirmatrelvir-ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir-ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.
| S-EPMC9328465 | biostudies-literature
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:The purpose of this study was to identify miRNAs that were dysregulated after the onset of COVID-19 and thus potentially be used for risk stratification (i.e., mortality). Therefore, we conducted a multi-center, retrospective longitudinal cohort study enrolling 142 patients with laboratory-confirmed SARS-CoV-2 infection who presented to two Canadian hospitals from May 2020 – December 2020 along with a cohort of 27 SARS-CoV-2 patients with mild upper respiratory tract symptoms and 69 SARS-CoV-2-negative patients from the ICU. Blood was biobanked from SARS-CoV-2 positive patients in the emergency department (mild), ward (moderate) or intensive care unit (severe). Assessment of miRNA expression and co-regulatory network generation revealed significant transcriptome dyregulation in pateints with severe COVID-19 that was largely different from SARS-CoV-2 negative patients in the ICU.
2022-04-08 | GSE178246 | GEO