{"doi":"10.1016/j.immuni.2020.11.017","title":"Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19","abstract":"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.","journal":"Immunity","year":2020,"id":2285,"datarank":0.90095297394026,"base_score":6.0063531596017325,"endowment":6.0063531596017325,"self_citation_contribution":0.90095297394026,"citation_network_contribution":0.0,"self_endowment_contribution":0.90095297394026,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":405,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.305,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":28392,"name":"Neha Mishra","orcid":"0000-0002-7436-1066","position":1,"is_corresponding":false},{"id":28393,"name":"Florian Tran","orcid":"0000-0002-3735-9872","position":2,"is_corresponding":false},{"id":28394,"name":"Thomas Bahmer","orcid":"0000-0002-7677-7057","position":3,"is_corresponding":false},{"id":28395,"name":"Lena Best","orcid":"0000-0003-2772-153X","position":4,"is_corresponding":false},{"id":28396,"name":"Johanna I. 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