Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19

Frishberg A, Kooistra E, Nuesch-Germano M, Pecht T, Milman N, Reusch N, Warnat-Herresthal S, Bruse N, Haendler K, Theis H, Kraut M, Van Rijssen E, Van Cranenbroek B, Koenen HJ, Heesakkers H, Van Den Boogaard M, Zegers M, Pickkers P, Becker M, Aschenbrenner AC, Ulas T, Theis FJ, Shen-Orr SS, Schultze JL, Kox M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Medicine Elsevier

Book Volume: 3

Article Number: 100652

Journal Issue: 6

DOI: 10.1016/j.xcrm.2022.100652

Abstract

Disease recovery dynamics are often difficult to assess, as patients display heterogeneous recovery courses. To model recovery dynamics, exemplified by severe COVID-19, we apply a computational scheme on longitudinally sampled blood transcriptomes, generating recovery states, which we then link to cellular and molecular mechanisms, presenting a framework for studying the kinetics of recovery compared with non-recovery over time and long-term effects of the disease. Specifically, a decrease in mature neutrophils is the strongest cellular effect during recovery, with direct implications on disease outcome. Furthermore, we present strong indications for global regulatory changes in gene programs, decoupled from cell compositional changes, including an early rise in T cell activation and differentiation, resulting in immune rebalancing between interferon and NF-κB activity and restoration of cell homeostasis. Overall, we present a clinically relevant computational framework for modeling disease recovery, paving the way for future studies of the recovery dynamics in other diseases and tissues.

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Radboud University Nijmegen NL Netherlands (NL) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Frishberg, A., Kooistra, E., Nuesch-Germano, M., Pecht, T., Milman, N., Reusch, N.,... Kox, M. (2022). Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19. Cell Reports Medicine, 3(6). https://doi.org/10.1016/j.xcrm.2022.100652

MLA:

Frishberg, Amit, et al. "Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19." Cell Reports Medicine 3.6 (2022).

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