Dataset Information

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.

SUBMITTER: Bernardes JP

PROVIDER: S-EPMC7689306 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Bernardes Joana P JP Mishra Neha N Tran Florian F Bahmer Thomas T Best Lena L Blase Johanna I JI Bordoni Dora D Franzenburg Jeanette J Geisen Ulf U Josephs-Spaulding Jonathan J Köhler Philipp P Künstner Axel A Rosati Elisa E Aschenbrenner Anna C AC Bacher Petra P Baran Nathan N Boysen Teide T Brandt Burkhard B Bruse Niklas N Dörr Jonathan J Dräger Andreas A Elke Gunnar G Ellinghaus David D Fischer Julia J Forster Michael M Franke Andre A Franzenburg Sören S Frey Norbert N Friedrichs Anette A Fuß Janina J Glück Andreas A Hamm Jacob J Hinrichsen Finn F Hoeppner Marc P MP Imm Simon S Junker Ralf R Kaiser Sina S Kan Ying H YH Knoll Rainer R Lange Christoph C Laue Georg G Lier Clemens C Lindner Matthias M Marinos Georgios G Markewitz Robert R Nattermann Jacob J Noth Rainer R Pickkers Peter P Rabe Klaus F KF Renz Alina A Röcken Christoph C Rupp Jan J Schaffarzyk Annika A Scheffold Alexander A Schulte-Schrepping Jonas J Schunk Domagoj D Skowasch Dirk D Ulas Thomas T Wandinger Klaus-Peter KP Wittig Michael M Zimmermann Johannes J Busch Hauke H Hoyer Bimba F BF Kaleta Christoph C Heyckendorf Jan J Kox Matthijs M Rybniker Jan J Schreiber Stefan S Schultze Joachim L JL Rosenstiel Philip P

Immunity 20201126 6

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 i ...[more]

PMID: 33296687

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Project description:Most adults experience episodes of gingivitis, which can progress to the irreversible, chronic state of periodontitis, yet roles of plaque in gingivitis onset and progression to periodontitis remain elusive. Here, we longitudinally profiled the plaque metagenome, the plaque metabolome, and salivary cytokines in 40 adults who transited from naturally occurring gingivitis (NG) to healthy gingivae (baseline) and then to experimental gingivitis (EG). During EG, rapid and consistent alterations in plaque microbiota, metabolites, and salivary cytokines emerged as early as 24 to 72 h after oral-hygiene pause, defining an asymptomatic suboptimal health (SoH) stage of the gingivae. SoH features a swift, full activation of 11 salivary cytokines but a steep synergetic decrease of plaque-derived betaine and Rothia spp., suggesting an anti-gum inflammation mechanism by health-promoting symbionts. Global, cross-cohort meta-analysis revealed, at SoH, a greatly elevated microbiome-based periodontitis index driven by its convergence of both taxonomical and functional profiles toward the periodontitis microbiome. Finally, post-SoH gingivitis development accelerates oral microbiota aging by over 1 year within 28 days, with Rothia spp. depletion and Porphyromonas gingivalis elevation as hallmarks. Thus, the microbiome-defined, transient gum SoH stage is a crucial link among gingivitis, periodontitis, and aging.IMPORTANCE A significant portion of world population still fails to brush teeth daily. As a result, the majority of the global adult population is afflicted with chronic gingivitis, and if it is left untreated, some of them will eventually suffer from periodontitis. Here, we identified periodontitis-like microbiome dysbiosis in an asymptomatic SoH stage as early as 24 to 72 h after oral-hygiene pause. SoH features a swift, full activation of multiple salivary cytokines but a steep synergetic decrease of plaque-derived betaine and Rothia spp. The microbial ecology during early gingivitis is highly similar to that in periodontitis under both taxonomical and functional contexts. Unexpectedly, exposures to gingivitis can accelerate over 10-fold the normal rate of oral microbiota aging. Our findings underscore the importance of intervening at the SoH stage of gingivitis via proper oral-hygiene practices on a daily basis, so as to maintain a periodontitis-preventive plaque and ensure the healthy aging of the oral ecosystem.

Dataset Information

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

Publications

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

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