Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression.

Background: Obesity affects the course of critical illnesses. We aimed to estimate the association of obesity with the severity and mortality in coronavirus disease 2019 (COVID-19) patients. Data Sources: A systematic search was conducted from the inception of the COVID-19 pandemic through to 13 October 2021, on 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. Study Selection and Data Extraction: Full-length articles focusing on the association of obesity and outcome in COVID-19 patients were included. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for study selection and data extraction. Our Population of interest were COVID-19 positive patients, obesity is our Intervention/Exposure point, Comparators are Non-obese vs obese patients The chief outcome of the study was the severity of the confirmed COVID-19 positive hospitalized patients in terms of admission to the intensive care unit (ICU) or the requirement of invasive mechanical ventilation/intubation with obesity. All-cause mortality in COVID-19 positive hospitalized patients with obesity was the secondary outcome of the study. Results: In total, 3,140,413 patients from 167 studies were included in the study. Obesity was associated with an increased risk of severe disease (RR=1.52, 95% CI 1.41-1.63, p<0.001, I2 = 97%). Similarly, high mortality was observed in obese patients (RR=1.09, 95% CI 1.02-1.16, p=0.006, I2 = 97%). In multivariate meta-regression on severity, the covariate of the female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2 = 40% of the between-study heterogeneity for severity. The aforementioned covariates were found to be significant for mortality as well, and these covariates collectively explained R2 = 50% of the between-study variability for mortality. Conclusions: Our 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 improvement of guidelines for patient care management is recommended.

A Case Series of Elizabethkingia meningosepticum Bacteremia in the Cancer Population.

Elizabethkingia meningosepticum (E. meningosepticum) is a ubiquitous microorganism previously known as Chryseobacterium meningosepticum. It is emerging as a pathogen responsible for bacteremia in the immunocompromised population, particularly in cancer patients and those with a history of prolonged hospital stay and frequent instrumentations. A retrospective chart review of all cases over 10 years at the Moffitt Cancer Center showed a total of three patients with E. meningosepticum infection. The first patient (history of multiple myeloma) underwent endoscopy complicated by aspiration pneumonia and positive blood culture for E. meningosepticum infection. The second patient (current acute myelogenous leukemia) had neutropenic fever in the setting of a recent chest port infection. Blood culture from the chest port showed E. meningosepticum. The third patient (history of esophageal adenocarcinoma and acute myelogenous leukemia) had a history of recent pneumonia and cellulitis who presented with recurrent neutropenic fever. Blood culture was positive for E. meningosepticum. E. meningosepticum bacteremia has a high 28-day mortality rate (41%). As these three cases illustrate, early identification of the pathogen along with empiric treatment with a fluoroquinolone and/or minocycline is indicated to reduce morbidity and mortality.

Atypical Thyroid Function Tests and Thyroid Hormone Resistance.

Clinical interpretation of thyroid labs is usually straightforward. However, there are rare instances when the atypical profile of thyroid labs warrants systematic investigation to determine the underlying cause. We report the case of a 90-year-old Caucasian male with a chronic history of atrial fibrillation with chronic pacemaker dependence who presented with significantly elevated free thyroxine level (>7.77 ng/dL) but normal thyroid-stimulating hormone level (2.15 µIU/mL). After ruling out pituitary tumors and artifactual errors due to lab interference, the diagnosis of thyroid hormone resistance was made.

Mortality Benefit of Convalescent Plasma in COVID-19: A Systematic Review and Meta-Analysis.

Importance/Background: With a scarcity of high-grade evidence for COVID-19 treatment, researchers and health care providers across the world have resorted to classical and historical interventions. Immunotherapy with convalescent plasma (CPT) is one such therapeutic option. Methods: A systematized search was conducted for articles published between December 2019 and 18th January 2021 focusing on convalescent plasma efficacy and safety in COVID-19. The primary outcomes were defined as mortality benefit in patients treated with convalescent plasma compared to standard therapy/placebo. The secondary outcome was pooled mortality rate and the adverse event rate in convalescent plasma-treated patients. Results: A total of 27,706 patients were included in the qualitative analysis, and a total of 3,262 (2,127 in convalescent plasma-treated patients and 1,135 in the non-convalescent plasma/control group) patients died. The quantitative synthesis in 23 studies showed that the odds of mortality in patients who received plasma therapy were significantly lower than those in patients who did not receive plasma therapy [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.53-0.80, p < 0.0001, I 2 = 15%). The mortality benefit remains the same even for 14 trials/prospective studies (OR 0.59, 95% CI 0.43-0.81, p = 0.001, I 2 = 22%) as well as for nine case series/retrospective observational studies (OR 0.78, 95% CI 0.65-0.94, p = 0.01, I 2 = 0%). However, in a subgroup analysis for 10 randomized controlled trials (RCTs), there was no statistically significant reduction in mortality between the CPT group compared to the non-CPT group (OR 0.76, 95% CI 0.53-1.08, p = 0.13, I 2 = 7%). Furthermore, the sensitivity analysis of 10 RCTs, excluding the study with the highest statistical weight, displayed a lower mortality rate compared to that of non-CPT COVID-19 patients (OR 0.64, 95% CI 0.42-0.97, p = 0.04, I 2 = 0%). The observed pooled mortality rate was 12.9% (95% CI 9.7-16.9%), and the pooled adverse event rate was 6.1% (95% CI 3.2-11.6), with significant heterogeneity. Conclusions and Relevance: Our systemic review and meta-analysis suggests that CPT could be an effective therapeutic option with promising evidence on the safety and reduced mortality in concomitant treatment for COVID-19 along with antiviral/antimicrobial drugs, steroids, and other supportive care. Future exploratory studies could benefit from more standardized reporting, especially in terms of the timing of interventions and clinically relevant outcomes, like days until discharge from the hospital and improvement of clinical symptoms.

Mortality and Severity in COVID-19 Patients on ACEIs and ARBs-A Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

Purpose: The primary objective of this systematic review is to assess association of mortality in COVID-19 patients on Angiotensin-converting-enzyme inhibitors (ACEIs) and Angiotensin-II receptor blockers (ARBs). A secondary objective is to assess associations with higher severity of the disease in COVID-19 patients. Materials and Methods: We searched multiple COVID-19 databases (WHO, CDC, LIT-COVID) for longitudinal studies globally 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. Result: Our findings showed that the use of ACEIs/ARBs did not significantly influence either mortality (OR = 1.16 95% CI 0.94-1.44, p = 0.15, I 2 = 93.2%) or severity (OR = 1.18, 95% CI 0.94-1.48, p = 0.15, I 2 = 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. Conclusion: We found no association of mortality or severity in COVID-19 patients taking ACEIs/ARBs.

Novel and Controversial Therapies in COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease (COVID-19) pandemic, which has led scientists all over the world to push for the identification of novel therapies for COVID-19. The lack of a vaccine and specific treatment has led to a surge of novel therapies and their publicity in recent times. Under these unprecedented circumstances, a myriad of drugs used for other diseases is being evaluated and repositioned to treat COVID-19 (example- Remdesivir, Baricitinib). While multiple trials for potential drugs and vaccines are ongoing, and there are many unproven remedies with little or no supporting evidence. Presently, discussions are revolving around the use of multivitamins (Vitamin, C, D, A), minerals (selenium, zinc), probiotics, flavonoids, polyphenols, and herbal remedies (curcumin, artemisinin, herbal drinks). Our review delves further into the details of some of these controversial therapies for COVID-19.

Mortality Benefit of Remdesivir in COVID-19: A Systematic Review and Meta-Analysis.

Importance/Background: During current public health emergency of COVID-19 pandemic, repurposing of existing antiviral drugs may be an efficient strategy since there is no proven effective treatment. Published literature shows Remdesivir has broad-spectrum antiviral activity against numerous RNA viruses and has been recently recognized as a promising therapy against SARS-CoV-2. Methods: A systematic search was conducted for full length manuscripts published between inception and July 19th, 2020 focussing on efficacy and safety of Remdesivir in COVID-19. The primary outcomes were defined as mortality rate and median days to recovery based on the available pooled data. The secondary outcome was adverse events rate and drug discontinuation rate. Statistical Analysis: All outcomes were performed using Comprehensive Meta-Analysis software package (Bio stat, Englewood, NJ, USA). Results: A total of 1,895 patients from 9 studies were included in this qualitative synthesis. In patients treated with Remdesivir, the mean recovery time was 15.84 days (95% CI 11.68-20, SE 2.12; I 2 = 97.24) and the pooled mortality rate was 11.3% (95% CI 7.9-16%; I 2 = 74.85). However, treatment with Remdesivir was associated with adverse effects (55.3%, 95% CI 31.5-76.9%; I 2 = 97.66) eventually warranting the discontinuation of the drug (17.8%, 95% CI 8.6-33.1%; I 2 = 95.64). The meta-analysis of three clinical trials indicated that administration of Remdesivir significantly reduces the mortality compared to the placebo (OR 0.70, 95% CI 0.58-0.84, p ≤ 0.001; I 2 = 16.6). Conclusions and Relevance: The result of contemporary meta-analysis suggests mortality benefit with Remdesivir in COVID-19 and median recovery time was over 2 weeks. The pooled mortality with Remdesivir was found to be very low, and this analysis can shed light on this potential treatment for COVID-19 patients.