Objective The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. Design In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. Results A total of 120 patients were included in the trial, 60 of which were assigned to Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden was significantly lower in Ammonium Chloride group corresponding to odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively. Conclusion The findings of this advocates the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.

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Background Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients. Methods Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations. Results High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway. Discussion The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.

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Introduction: The rapid worldwide spread of COVID-19 has caused a global health crisis. Unfortunately, no vaccine or special antiviral drug has been developed against COVID-19 to date, symptomatic supportive care has been the most common treatment. Objectives: the purpose of this systematic review aims to provide a timely, rigorous, and continuously updated summary of the available evidence on the role of vitamin C in treating patients with COVID-19. Methods: In this review, we identified studies published in 2020 that describe on the relationship between COVID-19 and vitamin C. We searched PubMed, Google Scholar, Scopus, Magiran, SID and Web of Science for research articles published up to 23 December 2020 using the keywords of vitamin C, COVID-19, SARS-COV-2 and coronavirus 2. Results: At the initial stage of screening, 181articles were excluded after reviewing the title and removing irrelevant and duplicate titles, 52 articles were selected to review the abstract. After reviewing the abstract (or in articles without abstracts after reviewing the original text), nine articles were finally considered suitable for this purpose and were reviewed and finalized. Vitamin C is a pivotal component of the immune system, with proven antioxidant, cytokine storm suppressor and anti-inflammatory properties and has been tested in numerous studies for its role in severe sepsis and ICU care, especially when used as a continuous high-dose intravenous infusion. In addition, some studies indicated high-dose intravenous vitamin C treatment was associated with fewer days on mechanical ventilation, shorter ICU stay, and earlier recovery compared to the average length of mechanical ventilation, disease duration, and ICU stay in critical COVID-19 patients. Conclusion: Vitamin C can significantly improve clinical symptoms, inflammatory response, immune and organ function in COVID-19 patients. In patients affected with COVID-19, high-dose intravenous vitamin C is expected to improve pulmonary function and reduce mortality for patients with COVID-19 and can be beneficial in aspects of inflammatory response, immune and organ function for aggravation of COVID-19 patients, however further clinical trials are necessary.