Outcomes of Heart Failure in COVID-19 Patients: An Appalachian Experience.

Background: The Southeastern rural areas of the USA have a higher prevalence of heart failure (HF). Coronavirus disease 2019 (COVID-19) infection is associated with poor outcomes in patients with HF. Our study aimed to compare the outcomes of hospitalized HF patients with and without COVID-19 infection specifically in rural parts of the USA. Methods: We conducted a retrospective cohort study of HF patients with and without COVID-19 hospitalized in Southeastern rural parts of the USA by using the Appalachian Regional Healthcare System. Analyses were stratified by waves from April 1, 2020 to May 31, 2021, and from June 1, 2021 to October 19, 2021. Results: Of the 14,379 patients hospitalized with HF, 6% had concomitant COVID-19 infection. We found that HF patients with COVID-19 had higher mortality rate compared to those without COVID-19 (21.8% versus 3.8%, respectively, P < 0.01). Additionally, hospital resource utilization was significantly higher in HF patients with COVID-19 compared to HF patients without COVID-19 with intensive care unit (ICU) utilization of 21.6% versus 13.8%, P < 0.01, mechanical ventilation use of 17.3% versus 6.2%, P < 0.01, and vasopressor/inotrope use of 16.8% versus 7.9%, P < 0.01. A lower percentage of those with COVID-19 were discharged home compared to those without a COVID-19 diagnosis (63.4% versus 72.0%, respectively). There was a six-fold greater odds of dying in the first wave and seven-fold greater odds of dying in the second wave. Conclusions: Our study confirms previous findings of poor outcome in HF patients with COVID-19. There is a need for review of healthcare resources in rural hospitals which already face numerous healthcare challenges.

Optimization and validation of RT-LAMP assay for diagnosis of SARS-CoV2 including the globally dominant Delta variant.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 pandemic, has infected more than 179 million people worldwide. Testing of infected individuals is crucial for identification and isolation, thereby preventing further spread of the disease. Presently, Taqman™ Reverse Transcription Real Time PCR is considered gold standard, and is the most common technique used for molecular testing of COVID-19, though it requires sophisticated equipments, expertise and is also relatively expensive. OBJECTIVE: Development and optimization of an alternate molecular testing method for the diagnosis of COVID-19, through a two step Reverse Transcription Loop-mediated isothermal AMPlification (RT-LAMP). RESULTS: Primers for LAMP were carefully designed for discrimination from other closely related human pathogenic coronaviruses. Care was also taken that primer binding sites are present in conserved regions of SARS-CoV2. Our analysis shows that the primer binding sites are well conserved in all the variants of concern (VOC) and variants of interest (VOI), notified by World Health Organization (WHO). These lineages include B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427/B.1.429, P.2, B.1.525, P.3, B.1.526 and B.1.617.1. Various DNA polymerases with strand displacement activity were evaluated and conditions were optimized for LAMP amplification and visualization. Different LAMP primer sets were also evaluated using synthetic templates as well as patient samples. CONCLUSION: In a double blind study, the RT-LAMP assay was validated on more than 150 patient samples at two different sites. The RT-LAMP assay appeared to be 89.2% accurate when compared to the Taqman™ rt-RT-PCR assay.

Regulation of Tissue Inflammation by 12-Lipoxygenases.

Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells-a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role.