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Coronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I-converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.

Introduction:Etomidate is usually preferred in the induction of cardiac compromised patients due to its relative cardiovascular stability. However, the use of this drug has been limited as etomidate induces suppression of cortisol biosynthesis as a result of blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazole radical of etomidate. This study was carried out to observe the effect of Vitamin C on adrenal suppression after etomidate induction in patients undergoing cardiac surgery.Materials and Methods:A total of 78 patients were randomly distributed into two groups. Group-I received oral Vitamin C (500 mg) twice daily and Group-II received antacid tablet as placebo twice daily instead of Vitamin C for 7 consecutive days prior to surgery till morning of surgery. Patients of both the groups induced with etomidate (0.1–0.3 mg/kg). Blood cortisol was estimated at different points of time till 24th postinduction hour/blood lactate, glucose, hemodynamic parameters, and perioperative outcomes were assessed.Results:Data of seventy patients (n = 35 in each group) were finally analyzed. Cortisol level is statistically significantly higher in Group-I (69.51 ± 7.65) as compared to Group-II (27.74 ± 4.72) (P < 0.05) in the 1st postinduction hour. In Group-II, cortisol was consistently lower for 1st 24 postinduction hour. Total adrenaline requirement was statistically significantly high in Group-II. Time of extubation, length of Intensive Care Unit stay arrhythmia was similar in both the groups.Conclusion:Vitamin C effectively inhibits etomidate-induced adrenal suppression in cardiac patients, thereby etomidate can be used as a safe alternative for induction in cardiac surgery under cardiopulmonary bypass when pretreated with Vitamin C.

BackgroundRecent advances in the functional analyses of endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs), have provided a new perspective on the crucial roles of RNA in gene regulation. Consequently, LncRNA deregulation is a key factor in various diseases, including pulmonary disorders like Cystic Fibrosis (CF). CF is the most common life limiting recessive disease in the U.S., and is due to mutations in the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction.MethodsHere we report a distinct LncRNA signature and corresponding mRNAs that distinguishes CF lung (airway and parenchyma) tissues from matched non-CF controls (n = 4 each group), generated by microarray specific for LncRNAs which includes corresponding mRNA expressions. In silico analyses of the cellular processes that are impacted by these LncRNAs was performed using Gene Ontology (GO). A selected subset of LncRNAs were validated by quantitative real-time PCR.ResultsWe have identified 636 LncRNAs differentially expressed in CF airway epithelium and 1974 in CF lung parenchyma compared to matched non-CF controls (fold change ≥2, p < 0.05), majority of which (> 50%) are intergenic. Interestingly, 15 of these differentially expressed LncRNAs and 9 coding mRNAs are common to airway and parenchyma tissues. GO analyses indicates that signaling pathways and cell membrane functions are significantly affected by the alteration in LncRNA expressions in CF lung tissues. Seven of the differentially expressed LncRNAs, exhibit similar expression trends in CFBE41o- compared to control cells.ConclusionUnderstanding the mechanisms by which these LncRNAs regulate CF disease phenotype will help develop novel therapeutic targets for CF and related pulmonary diseases, such as COPD and Asthma.

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