By Pooja Toshniwal PahariaDec 6 2022Reviewed by Danielle Ellis, B.Sc. In a recent study posted to JAMA Network Open, researchers assessed the effect of remdesivir on inpatient coronavirus disease 2019 -associated mortality among individuals hospitalized with severe acute respiratory syndrome coronavirus 2 infections in an enormous dataset of United States residents beyond clinical trial settings.
About the study In the present retrospective cohort study, researchers investigated whether remdesivir medication could reduce inpatient death rates among hospitalized COVID-19 patients. The dates of initiating remdesivir treatment during the inpatient stay for remdesivir-treated individuals and the concordant hospitalization dates for controls were considered index dates. Individuals prescribed as part of clinical trials, history of SARS-CoV-2 infection-associated inpatient hospitalizations or previous remdesivir use were excluded from the analysis.
The majority of the study participants were male, with an average age of 67 years. The median values for the duration of follow-up in the remdesivir-treated group and control group were six days and five days, respectively. A total of 3,557 deaths and 3,775 deaths were reported in the remdesivir group and control group, respectively.
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Source: NewsMedical - 🏆 19. / 71 Read more »
Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines - Genome MedicineBackground COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about the epigenetic alterations that occur in these cells during hyperinflammatory responses in severe COVID-19 patients. Methods In this study, we obtained the DNA methylome and transcriptome of peripheral blood monocytes from severe COVID-19 patients. DNA samples extracted from CD14 + CD15- monocytes of 48 severe COVID-19 patients and 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. In parallel, single-cell transcriptomics of 10 severe COVID-19 patients were generated. CellPhoneDB was used to infer changes in the crosstalk between monocytes and other immune cell types. Results We observed DNA methylation changes in CpG sites associated with interferon-related genes and genes associated with antigen presentation, concordant with gene expression changes. These changes significantly overlapped with those occurring in bacterial sepsis, although specific DNA methylation alterations in genes specific to viral infection were also identified. We also found these alterations to comprise some of the DNA methylation changes occurring during myeloid differentiation and under the influence of inflammatory cytokines. A progression of DNA methylation alterations in relation to the Sequential Organ Failure Assessment (SOFA) score was found to be related to interferon-related genes and T-helper 1 cell cytokine production. CellPhoneDB analysis of the single-cell transcriptomes of other immune cell types suggested the existence of altered crosstalk between monocytes and other cell types like NK cells and regulatory T cells. Conclusion Our findings show the occurrence of an epigenetic and transcriptional reprogramming of peripheral blood monocytes, which could be associated with the
Source: BioMedCentral - 🏆 22. / 71 Read more »