Longitudinal multi-omics identifies responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories [methylation]

To help characterise the temporal dynamics of host response during COVID-19, we performed a longitudinal DNA methylation analysis in a cohort of 12 patients. DNA was extracted from peripheral blood sampled at up to 5 time points per patient. At each sample point, a patient’s disease trajectory, “pseudotime”, was categorised according to clinical parameters. DNA methylation profiling by Illumina Bead Arrays was performed on each sample. We found CpG sites hypomethylated during COVID-19 were highly enriched in cis of transcripts related to positive regulation of TNF secretion and innate immune signalling, indicating potential long-term regulation of immunological misfiring by epigenetic processes. 6 patients were sampled at days 0, 2, 7, 10, 13 and/or at discharge. 6 healthy donors were sampled at a single time point.