Integrated multiomics implicates dysregulation of ECM and cell adhesion pathways as drivers of severe COVID-associated kidney injury (preprint)

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

An Analysis of Online Foreign Language Syllabi

This qualitative study explored the design and delivery of the online foreign language (FL) syllabus in a teacher education institution in the Philippines during the emergency distance education (EDE) amid the COVID-19 pandemic. The FL syllabi used by the FL instructors in the university were collected by the researchers and analyzed through a modified online syllabus rubric based on the Online SUNY Course Quality Review Rubric (OSCQR) and Quality Online Learning and Teaching (QOLT) Rubric to examine the different teaching and learning facets in their syllabus design. Afterward, twelve students enrolled in the different FL courses and three FL instructors of the university were interviewed to gather data for the implementation of the online FL syllabi. With the thematic method of analysis, data gathered from both the document analysis and the interview conducted were examined. The results showed that FL instructors considered the different learning and teaching features in designing their syllabi during EDE. It also exhibits that FL syllabi design and delivery remained parallel even if there were some modifications and improvisations along with the implementation of the documents to adapt to the current learning environment.