Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19

Sequencing genomes from mixed DNA samples - evaluating the metagenome skimming approach in lichenized fungi

The metagenome skimming approach, i.e. low coverage shotgun sequencing of multi-species assemblages and subsequent reconstruction of individual genomes, is increasingly used for in-depth genomic characterization of ecological communities. This approach is a promising tool for reconstructing genomes of facultative symbionts, such as lichen-forming fungi, from metagenomic reads. However, no study has so far tested accuracy and completeness of assemblies based on metagenomic sequences compared to assemblies based on pure culture strains of lichenized fungi. Here we assembled the genomes of Evernia prunastri and Pseudevernia furfuracea based on metagenomic sequences derived from whole lichen thalli. We extracted fungal contigs using two different taxonomic binning methods, and performed gene prediction on the fungal contig subsets. We then assessed quality and completeness of the metagenome-based assemblies using genome assemblies as reference which are based on pure culture strains of the two fungal species. Our comparison showed that we were able to reconstruct fungal genomes from uncultured lichen thalli, and also cover most of the gene space (86–90%). Metagenome skimming will facilitate genome mining, comparative (phylo)genomics, and population genetics of lichen-forming fungi by circumventing the time-consuming, sometimes unfeasible, step of aposymbiotic cultivation