Project description:The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.
Project description:The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3-9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In-hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81-1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56-1.17, P = 0.26). COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.
Project description:IntroductionColchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients.MethodsIn accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta-analysis was conducted using Review Manager 5.4.ResultsIn total, six studies were included, of which four reported c-reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = -0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = -0.85, p < 0.001). Finally, the D-dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = -0.9, p < 0.001).ConclusionColchicine has efficacy in reducing inflammatory biomarkers observed in moderate-to-severe COVID-19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID-19 treatment.
Project description:The increasing COVID-19 cases in the USA have led to overburdening of healthcare in regard to invasive mechanical ventilation (IMV) utilization as well as mortality. We aim to identify risk factors associated with poor outcomes (IMV and mortality) of COVID-19 hospitalized patients. A meta-analysis of observational studies with epidemiological characteristics of COVID-19 in PubMed, Web of Science, Scopus, and medRxiv from December 1, 2019 to May 31, 2020 following MOOSE guidelines was conducted. Twenty-nine full-text studies detailing epidemiological characteristics, symptoms, comorbidities, complications, and outcomes were included. Meta-regression was performed to evaluate effects of comorbidities, and complications on outcomes using a random-effects model. The pooled correlation coefficient (r), 95% CI, and OR were calculated. Of 29 studies (12,258 confirmed cases), 17 reported IMV and 21 reported deaths. The pooled prevalence of IMV was 23.3% (95% CI: 17.1-30.9%), and mortality was 13% (9.3-18%). The age-adjusted meta-regression models showed significant association of mortality with male (r: 0.14; OR: 1.15; 95% CI: 1.07-1.23; I 2: 95.2%), comorbidities including pre-existing cerebrovascular disease (r: 0.35; 1.42 (1.14-1.77); I 2: 96.1%), and chronic liver disease (r: 0.08; 1.08 (1.01-1.17); I 2: 96.23%), complications like septic shock (r: 0.099; 1.10 (1.02-1.2); I 2: 78.12%) and ARDS (r: 0.04; 1.04 (1.02-1.06); I 2: 90.3%), ICU admissions (r: 0.03; 1.03 (1.03-1.05); I 2: 95.21%), and IMV utilization (r: 0.05; 1.05 (1.03-1.07); I 2: 89.80%). Similarly, male (r: 0.08; 1.08 (1.02-1.15); I 2: 95%), comorbidities like pre-existing cerebrovascular disease (r: 0.29; 1.34 (1.09-1.63); I 2:93.4%), and cardiovascular disease (r: 0.28; 1.32 (1.1-1.58); I 2: 89.7%) had higher odds of IMV utilization. COVID-19 patients with comorbidities including cardiovascular disease, cerebrovascular disease, and chronic liver disease had poor outcomes. Diabetes and hypertension had higher prevalence but no association with mortality and IMV. Our study results will be helpful in right allocation of resources towards patients who need them the most.
Project description:Objective: There exists controversy about the pathophysiology and lung mechanics of COVID-19 associated acute respiratory distress syndrome (ARDS), because some report severe hypoxemia with preserved respiratory system mechanics, contrasting with "classic" ARDS. We performed a detailed hourly analysis of the characteristics and time course of lung mechanics and biochemical analysis of patients requiring invasive mechanical ventilation (IMV) for COVID-19-associated ARDS, comparing survivors and non-survivors. Methods: Retrospective analysis of the data stored in the ICU information system of patients admitted in our hospital ICU that required IMV due to confirmed SARS-CoV-2 pneumonia between March 5th and April 30th, 2020. We compare respiratory system mechanics and gas exchange during the first ten days of IMV, discriminating volume and pressure controlled modes, between ICU survivors and non-survivors. Results: 140 patients were included, analyzing 11 138 respiratory mechanics recordings. Global mortality was 38.6%. Multivariate analysis showed that age (OR 1.092, 95% (CI 1.014-1.176)) and need of renal replacement therapies (OR 10.15, (95% CI 1.58-65.11)) were associated with higher mortality. Previous use of Angiotensin Converting Enzyme inhibitor (ACEI)/angiotensin-receptor blockers (ARBs) also seemed to show an increased mortality (OR 4.612, (95% CI 1.19-17.84)) although this significance was lost when stratifying by age. Respiratory variables start to diverge significantly between survivors and non-survivors after the 96 to 120 hours (hs) from mechanical ventilation initiation, particularly respiratory system compliance. In non survivors, mechanical power at 24 and 96 hs was higher regardless ventilatory mode. Conclusions: In patients admitted for SARS-CoV-2 pneumonia and requiring mechanical ventilation, non survivors have different respiratory system mechanics than survivors in the first 10 days of ICU admission. We propose a checkpoint at 96-120 hs to assess patients improvement or worsening in order to consider escalating to extracorporeal therapies.
Project description:Rationale: Initial reports of case fatality rates (CFRs) among adults with coronavirus disease (COVID-19) receiving invasive mechanical ventilation (IMV) are highly variable.Objectives: To examine the CFR of patients with COVID-19 receiving IMV.Methods: Two authors independently searched PubMed, Embase, medRxiv, bioRxiv, the COVID-19 living systematic review, and national registry databases. The primary outcome was the "reported CFR" for patients with confirmed COVID-19 requiring IMV. "Definitive hospital CFR" for patients with outcomes at hospital discharge was also investigated. Finally, CFR was analyzed by patient age, geographic region, and study quality on the basis of the Newcastle-Ottawa Scale.Measurements and Results: Sixty-nine studies were included, describing 57,420 adult patients with COVID-19 who received IMV. Overall reported CFR was estimated as 45% (95% confidence interval [CI], 39-52%). Fifty-four of 69 studies stated whether hospital outcomes were available but provided a definitive hospital outcome on only 13,120 (22.8%) of the total IMV patient population. Among studies in which age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI, 46.4-49.4%) in younger patients (age ≤40 yr) to 84.4% (95% CI, 83.3-85.4%) in older patients (age >80 yr). CFR was also higher in early COVID-19 epicenters. Overall heterogeneity is high (I2 >90%), with nonsignificant Egger's regression test suggesting no publication bias.Conclusions: Almost half of patients with COVID-19 receiving IMV died based on the reported CFR, but variable CFR reporting methods resulted in a wide range of CFRs between studies. The reported CFR was higher in older patients and in early pandemic epicenters, which may be influenced by limited ICU resources. Reporting of definitive outcomes on all patients would facilitate comparisons between studies.Systematic review registered with PROSPERO (CRD42020186997).
Project description:BackgroundInsight into COVID-19 intensive care unit (ICU) patient characteristics, rates and risks of invasive mechanical ventilation (IMV) and associated outcomes as well as any regional discrepancies is critical in this pandemic for individual case management and overall resource planning.Methods and findingsElectronic searches were performed for reports through May 1 2020 and reports on COVID-19 ICU admissions and outcomes were included using predefined search terms. Relevant data was subsequently extracted and pooled using fixed or random effects meta-analysis depending on heterogeneity. Study quality was assessed by the NIH tool and heterogeneity was assessed by I2 and Q tests. Baseline patient characteristics, ICU and IMV outcomes were pooled and meta-analyzed. Pooled odds ratios (pOR) were calculated for clinical features against ICU, IMV mortality. Subgroup analysis was carried out based on patient regions. A total of twenty-eight studies comprising 12,437 COVID-19 ICU admissions from seven countries were meta-analyzed. Pooled ICU admission rate was 21% [95% CI 0.12-0.34] and 69% of cases needed IMV [95% CI 0.61-0.75]. ICU and IMV mortality were 28.3% [95% CI 0.25-0.32], 43% [95% CI 0.29-0.58] and ICU, IMV duration was 7.78 [95% CI 6.99-8.63] and 10.12 [95% CI 7.08-13.16] days respectively. Besides confirming the significance of comorbidities and clinical findings of COVID-19 previously reported, we found the major correlates with ICU mortality were IMV [pOR 16.46, 95% CI 4.37-61.96], acute kidney injury (AKI) [pOR 12.47, 95% CI 1.52-102.7], and acute respiratory distress syndrome (ARDS) [pOR 6.52, 95% CI 2.66-16.01]. Subgroup analyses confirm significant regional discrepancies in outcomes.ConclusionsThis is a comprehensive systematic review and meta-analysis of COVID-19 ICU and IMV cases and associated outcomes. The significant association of AKI, ARDS and IMV with mortality has implications for ICU resource planning for AKI and ARDS as well as suggesting the need for further research into optimal ventilation strategies for COVID-19 patients in the ICU setting. Regional differences in outcome implies a need to develop region specific protocols for ventilatory support as well as overall treatment.
Project description:BackgroundOveractivation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome can lead to severe illness in patients with coronavirus disease-2019 (COVID-19). The NLRP3 inhibitor, colchicine, therefore, appears to be promising for the treatment of COVID-19.AimsWe aimed to perform a meta-analysis of randomized trials investigating the effect of colchicine in patients with COVID-19.Materials & methodsWe systematically searched electronic databases and clinical trial registries (up to October 17, 2021) for eligible studies. The outcomes of interest were all-cause mortality and duration of hospital stay. Meta-analysis with the random-effects model was used to estimate the pooled odds ratio (OR) of mortality and 95% confidence interval (CI). The pooled standardized mean difference of duration of hospital stay with 95% CI between colchicine users and non-colchicine users was estimated using Cohen's d index.ResultsThe meta-analyses revealed no significant difference in the odds of mortality (pooled OR = 0.76; 95% CI: 0.53-1.07), but a significant reduction in the duration of hospital stay with the use of colchicine (pooled standardized mean difference = -0.59; 95% CI: -1.06 to -0.13).Discussion and conclusionThe ability of colchicine to reduce the length of stay in hospitalized patients with COVID-19 is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. Nevertheless, such beneficial effects of colchicine did not translate into mortality benefits in patients with COVID-19.
Project description:There is mounting evidence that statin use is beneficial for COVID-19 outcomes. We performed a systematic review and meta-analysis to evaluate the association between statin use and mortality, intensive care unit (ICU) admission and mechanical ventilation in COVID-19 patients, on studies which provided covariate adjusted effect estimates, or performed propensity score matching. We searched PubMed, Embase, Web of Science and Scopus for studies and extracted odds or hazard ratios for specified outcome measures. Data synthesis was performed using a random-effects inverse variance method. Risk of bias, heterogeneity and publication bias were analyzed using standard methods. Our results show that statin use was associated with significant reductions in mortality (OR = 0.72, 95% CI: 0.67-0.77; HR = 0.74, 95% CI: 0.69, 0.79), ICU admission (OR = 0.94, 95% CI: 0.89-0.99; HR = 0.76, 95% CI: 0.60-0.96) and mechanical ventilation (OR = 0.84, 95% CI: 0.78-0.92; HR = 0.67, 95% CI: 0.47-0.97). Nevertheless, current retrospective studies are based on the antecedent use of statins prior to infection and/or continued use of statin after hospital admission. The results may not apply to the de novo commencement of statin treatment after developing COVID-19 infection. Prospective studies are lacking and necessary.
Project description:ObjectiveThis systematic review, with meta-analysis and meta-regression aims to evaluate the effect of colchicine administration on mortality in patients with coronavirus disease 2019 (COVID-19) and factors affecting the association.MethodsA systematic literature search using the PubMed, Scopus, and Embase databases were performed from inception of databases up until 3 March 2021. We included studies that fulfill all of the following criteria: 1) observational studies or randomized controlled trials (RCTs) that report COVID-19 patients, 2) reporting colchicine use, and 3) mortality within 30 days. There was no restriction on the age, inpatients or outpatients setting, and severity of diseases. The intervention was colchicine administration during treatment for COVID-19. The control was receiving placebo or standard of care. The outcome was mortality and the pooled effect estimate was reported as odds ratio (OR). Random-effects restricted maximum likelihood meta-regression was performed to evaluate factors affecting the pooled effect estimate.ResultsEight studies comprising of 5530 patients were included in this systematic review and meta-analysis. There were three RCTs and five observational studies. Pooled analysis showed that colchicine was associated with lower mortality in patients with COVID-19 (OR 0.47 [0.31, 0.72], p = 0.001; I2: 30.9, p = 0.181). Meta-regression analysis showed that the association between colchicine and mortality was reduced by increasing age (OR 0.92 [0.85, 1.00], p = 0.05), but not gender (reference: male, p = 0.999), diabetes (p = 0.376), hypertension (p = 0.133), and CAD (p = 0.354).ConclusionThis meta-analysis indicates that colchicine may reduce mortality in patients with COVID-19. Meta-regression analysis showed that the benefit was reduced as age increases.ProsperoCRD42021240609.