Effect of Anticoagulant Administration on the Mortality of Hospitalized Patients With COVID-19: An Updated Systematic Review and Meta-Analysis.
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ABSTRACT:
SUBMITTER: Jiang L
PROVIDER: S-EPMC8371681 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.
| S-EPMC8509118 | biostudies-literature
Project description:Background and aimsStatin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality.MethodsA systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus non-users.Results22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 ± 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58-100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Meta-analysis of 12 studies (n = 72,881, weighted age 65 ± 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities.ConclusionsThis meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients.
| S-EPMC8233054 | biostudies-literature
Project description:Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (-3.7 g/L, 95% CI, -5.3 to -2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.
| S-EPMC7280666 | biostudies-literature
Project description:ImportanceClinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.ObjectiveTo estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data sourcesTrials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study selectionEligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data extraction and synthesisIn this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main outcomes and measuresThe primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.ResultsA total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).Conclusions and relevanceIn this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.Trial registrationPROSPERO Identifier: CRD42021230155.
| S-EPMC8261689 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) is characterized by coagulopathy and thrombotic events. We examined factors associated with development of venous thromboembolism (VTE) in COVID-19 and to discern if higher dose of anticoagulation was beneficial in these patients.MethodsThis study involves an observational study of prospectively collected data in the setting of a large community hospital in a rural setting in Northeast Georgia with COVID-19 between March 1, 2020 and February 5, 2021. Anticoagulation dose (none, standard, intermediate, and therapeutic dosages) was studied in adult patients (≥ 18 years). We constructed multivariable logistic regression model to examine the association of clinical characteristics with VTE. To examine the effect of dose of anticoagulation in preventing VTE, we used inverse probability weighted regression adjustment.ResultsOf the 4,645 patients with COVID-19, 251 (5.4%) patients were found to have VTE. Of these, 91 had pulmonary embolism, 148 had deep venous thrombosis (DVT) and 12 had both. A total of 129 of VTE cases were diagnosed at admission. Of all admissions, 12.9% did not receive any DVT prophylaxis, 70.4% received prophylactic dose, 1.3% received intermediate dose and 15.5% received therapeutic dose. Male gender (odds ratio (OR): 1.55, 95% confidence interval (CI): 1.0 - 2.4, P = 0.04) and Black race (OR: 2.0, 95% CI: 1.2 - 3.4, P = 0.01), along with higher levels of lactate dehydrogenase (LDH) and D-dimer were associated with higher odds of developing VTE. Patients receiving steroids had lower rates of VTE (3.9% vs. 8.3%, P < 0.001). Use of intermediate or therapeutic anticoagulation was not associated with lower odds of developing VTE. However, patients on therapeutic anticoagulation had lower odds of in hospital mortality when compared to standard dose (OR: 0.47, 95% CI: 0.27 - 0.80, P = 0.006).ConclusionsIn COVID-19, D-dimer and LDH can be useful in predicting VTE. Steroids appear to have some protective role in development of VTE. Therapeutic anticoagulation did not result in lower rates of VTE but was associated with in-hospital mortality.
| S-EPMC8425807 | biostudies-literature
Project description:Tocilizumab has been repurposed against the 'cytokine storm' in the setting of coronavirus disease 2019 (COVID-19). Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID-19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non-ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate-to-critical COVID-19.
| S-EPMC8661720 | biostudies-literature
Project description:IntroductionFamotidine is a competitive histamine H2-receptor antagonist most commonly used for gastric acid suppression but thought to have potential efficacy in treating patients with Coronavirus disease 2019 (COVID-19). The aims of this systematic review and meta-analysis are to summarize the current literature and report clinical outcomes on the use of famotidine for treatment of hospitalized patients with COVID-19.MethodsFive databases were searched through February 12, 2021 to identify observational studies that reported on associations of famotidine use with outcomes in COVID-19. Meta-analysis was conducted for composite primary clinical outcome (e.g. rate of death, intubation, or intensive care unit admissions) and death separately, where either aggregate odds ratio (OR) or hazard ratio (HR) was calculated.ResultsFour studies, reporting on 46,435 total patients and 3,110 patients treated with famotidine, were included in this meta-analysis. There was no significant association between famotidine use and composite outcomes in patients with COVID-19: HR 0.63 (95% CI: 0.35, 1.16). Across the three studies that reported mortality separated from other endpoints, there was no association between famotidine use during hospitalization and risk of death-HR 0.67 (95% CI: 0.26, 1.73) and OR 0.79 (95% CI: 0.19, 3.34). Heterogeneity ranged from 83.69% to 88.07%.ConclusionBased on the existing observational studies, famotidine use is not associated with a reduced risk of mortality or combined outcome of mortality, intubation, and/or intensive care services in hospitalized individuals with COVID-19, though heterogeneity was high, and point estimates suggested a possible protective effect for the composite outcome that may not have been observed due to lack of power. Further randomized controlled trials (RCTs) may help determine the efficacy and safety of famotidine as a treatment for COVID-19 patients in various care settings of the disease.
| S-EPMC8568101 | biostudies-literature
Project description:The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9?±?8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p?<?0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.
| S-EPMC7899074 | biostudies-literature
Project description:BackgroundRandomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids.ObjectivesTo estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids.Data sourcesPubMed, Embase, Cochrane Library, and MedRxiv.Study eligibility criteriaEligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control).MethodsReviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days.ParticipantsTwenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively.ResultsAll but two studies included data with only indirect evidence for the comparison of interest.ConclusionsAmong hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.
| S-EPMC9293401 | biostudies-literature
Project description:There is increasing evidence for oral lesions and manifestations of COVID-19. The aim of this meta-analysis was to investigate the types of oral manifestations of COVID-19 and their prevalence. PubMed/Medline, Scopus, Web of Science, and Google Scholar databases were used to search for publications on oral manifestations in patients with PCR-confirmed COVID-19. A total of 310 records were selected, and 74 were included. Oral lesions in COVID-19 were classified according to their etiologies, including iatrogenic lesions caused by intubation and opportunistic infections. Of the included studies, 35 reported oral lesions probably caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) infection. Meta-analysis of prevalence data on oral manifestations and aphthous lesions indicated high heterogeneity, while meta-analysis of xerostomia prevalence data revealed a pooled prevalence, with considerable heterogeneity. In conclusion, the meta-analysis yielded high heterogeneity between studies: oral lesions yielded a prevalence of 0.33 (95% CI 0.11-0.60), xerostomia lesions a prevalence of 0.44 (95% CI 0.36-0.52) and aphthous lesions 0.10 (95% CI 0.01-0.24). In addition, a gap in the evidence regarding the prevalence of oral lesions in COVID-19 was identified and the need for further observational studies focusing on this issue and on the causal relationships between oral lesions and COVID-19 was highlighted.
| S-EPMC8424005 | biostudies-literature