Institutional Review Board and national radiation protection agency approval Z5-22462/2-2017-021 and Z5–22464/2020-047-G) was obtained prior to this study. Patients gave their written informed consent prior to study participation.illustrates COVID-19 patient selection. Between May 2020 and December 2020, patients of legal age that underwent chest CT at our institution as part of their diagnostic workup and with a clinically suspected COVID-19 infection were screened for study participation.
Exclusion criteria were a negative RT-PCR test within 2 days before the CT scan, pregnancy, lung cancer, and pneumothorax. Sixty patients with suspected COVID-19 infection were included in this study.Between October 2018 and January 2020, patients of legal age that underwent chest CT at our institution as part of their diagnostic workup were screened for study participation. All CT images of potential study participants were analysed for pathologic lung changes by three radiologists .
Attenuation-based images were additionally evaluated by using the winning neural network of the SIIM-FISABIO-RSNA COVID-19 Detection ChallengeThe quantitative dark-field coefficient was calculated according to Gassert et al.The area under the receiver operating characteristic curve was calculated for all three reading modalities, and AUC values were tested for differences with Obuchowski’s method for correlated and clustered ROC data.
As images were acquired in a clinical setting and COVID-19-associated lung changes change over time, reproduction of image acquisition is not feasible. Statistical analysis of acquired images, however, is reproducible.
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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
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