Association of Obesity with COVID-19 Severity and Mortality: A Systemic Review and Meta-Regression

ObjectiveTo estimate the association of obesity with severity (defined as use of invasive mechanical ventilation or intensive care unit admission) and all-cause mortality in coronavirus disease 2019 (COVID-19) patients. Patients and MethodsA systematic search was conducted from inception of COVID-19 pandemic through January 31st, 2021 for full-length articles focusing on the association of increased BMI/ Obesity and outcome in COVID-19 patients with help of various databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used for study selection and data extraction. The severity in hospitalized COVID-19 patients, such as requirement of invasive mechanical ventilation and intensive care unit admission with high BMI/ Obesity was the chief outcome. While all-cause mortality in COVID-19 hospitalized patients with high BMI/ Obesity was the secondary outcome. ResultsA total of 576,784 patients from 100 studies were included in this meta-analysis. Being obese was associated with increased risk of severe disease (RR=1.46, 95% CI 1.34-1.60, p<0.001, I2 = 92 %). Similarly, high mortality was observed in obese patients with COVID-19 disease (RR=1.12, 95% CI 1.06-1.19, p<0.001, I2 = 88%). In a multivariate meta-regression on severity outcome, the covariate of female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2= 50% of the between-study heterogeneity for severity. Similarly, for mortality outcome, covariate of female gender, proportion of pulmonary disease, diabetes, hypertension, and cardiovascular diseases were significant, these covariates collectively explained R2=53% of the between-study variability for mortality. ConclusionsOur findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and streamlining the management strategy and treatment guidelines to account for the impact of obesity in patient care management is recommended.

A Meta-analysis of Mortality, Need for ICU admission, Use of Mechanical Ventilation and Adverse Effects with Ivermectin Use in COVID-19 Patients

ImportanceRepurposing Ivermectin, a known anti-parasitic agent, for treating COVID-19 has demonstrated positive results in several studies. We aim to evaluate the benefit and risk of Ivermectin in COVID-19. MethodsWe conducted a systematic search for full-text manuscripts published from February 1, 2020, to August 15th, 2021 focusing on Ivermectin therapy against COVID-19. The primary outcomes were mortality, need for intensive care unit (ICU) admission; secondary outcomes were - adverse effects, need for mechanical ventilation, viral clearance, time to viral clearance, need for hospitalization, and length of hospital stay. Random-effects models were used for all analyses. ResultsWe included a total of 52 studies (n=17561) in the qualitative analysis, out of these, 44 studies (n=14019) were included in the meta-analysis. In the mortality meta-analysis (N=29), odds of death were lower in the Ivermectin-arm compared to control (OR 0.54, p=0.009). Although lower odds of mortality were observed in various subgroup analyses of RCTs, they did not reach statistical significance: therapeutic RCTs: mild-moderate COVID-19 (OR 0.31, p=0.06), therapeutic RCTs: severe/critical COVID-19 (OR 0.86, p=0.56), inpatient RCTs: mild-moderate COVID-19 (OR 0.18, p=0.08), inpatient RCTs: severe/critical COVID-19 (OR 0.86, p=0.56). Ivermectin, mostly as adjuvant therapy, was associated with higher odds of viral clearance (N=22) (OR 3.52, p=0.0002), shorter duration to achieve viral clearance (N=8) (MD - 4.12, p=0.02), reduced need for hospitalization (N=6) (OR 0.34, p=008). ConclusionOur meta-analysis suggests that the mortality benefit of Ivermectin in COVID-19 is uncertain. But as adjuvant therapy, Ivermectin may improve viral clearance and reduce the need for hospitalization. HighlightsO_ST_ABSWhat We Already Know about This TopicC_ST_ABSO_LICOVID-19 is an ongoing global pandemic, for which Ivermectin has been tried on a therapeutic and prophylactic basis. C_LIO_LIResults from several clinical trials and observational studies suggest that Ivermectin may improve survival and clinical outcomes with a good safety profile when compared with other treatments; however, the current evidence is limited.. C_LI What This Article Tells Us That Is NewO_LIThis systematic review and meta-analysis provide a summary of the latest literature on the efficacy and safety of Ivermectin use for COVID-19. C_LIO_LIBased on our analysis of the latest evidence, we found that Ivermectins benefit in reducing mortality cannot be concluded with confidence. However, as an adjuvant therapy it may help reduce the need for hospitalization, duration for viral clearance while increasing the likelihood of achieving viral clearance. C_LIO_LIWe need more high-quality data for conclusive evidence regarding the benefit of Ivermectin in reducing the need for ICU admissions, mechanical ventilation and duration of hospital stay in COVID-19 patients. C_LI

Mortality and Severity in COVID-19 Patients on ACEIs & ARBs - A Meta-Regression Analysis

PurposeThe primary objective of this review is to examine studies reporting association of mortality in COVID-19 patients with whether they were on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin II receptor blockers (ARBs). A secondary objective is to similarly access associations with higher severity of the disease in COVID-19 patients. Materials and MethodsWe searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for randomized trials and longitudinal studies from all over the world reporting mortality and severity published before January 18th, 2021. Meta-analyses were performed using 53 studies for mortality outcome and 43 for the severity outcome. Mantel-Haenszel odds ratios were generated to describe overall effect size using random effect models. To account for between study results variations, multivariate meta-Regression was performed with preselected covariates using maximum likelihood method for both the mortality and severity models. ResultOur findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR=1.16 95% CI 0.94 to 1.44, p= 0.15, I2 = 93.2%) or severity (OR=1.18, 95% CI 0.94 to 1.48 p= 0.15, I2 = 91.1%) in comparison to not being on ACEIs/ARBs in COVID-19 positive patients. Multivariate meta-regression for the mortality model demonstrated that 36% of between study variations could be explained by differences in age, gender, and proportion of heart diseases in the study samples. Multivariate meta-regression for the severity model demonstrated that 8% of between study variations could be explained by differences in age, proportion of diabetes, heart disease and study country in the study samples. ConclusionWe found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.