TY  - JOUR
AU  - Frishberg, Amit
AU  - Kooistra, Emma
AU  - Nuesch-Germano, Melanie
AU  - Pecht, Tal
AU  - Milman, Neta
AU  - Reusch, Nico
AU  - Warnat-Herresthal, Stefanie
AU  - Bruse, Niklas
AU  - Händler, Kristian
AU  - Theis, Heidi
AU  - Kraut, Michael
AU  - van Rijssen, Esther
AU  - van Cranenbroek, Bram
AU  - Koenen, Hans JPM.
AU  - Heesakkers, Hidde
AU  - van den Boogaard, Mark
AU  - Zegers, Marieke
AU  - Pickkers, Peter
AU  - Becker, Matthias Kai Holger
AU  - Aschenbrenner, Anna Christin
AU  - Ulas, Thomas
AU  - Theis, Fabian J.
AU  - Shen-Orr, Shai S.
AU  - Schultze, Joachim
AU  - Kox, Matthijs
TI  - Mature neutrophils and a NF-κB-to-IFN transition determine the unifying disease recovery dynamics in COVID-19
JO  - Cell reports
VL  - 3
IS  - 6
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - DZNE-2022-01179
SP  - 100652
PY  - 2022
N1  - (CC BY-NC-ND)
AB  - 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.
KW  - COVID-19
KW  - Cell Differentiation
KW  - Humans
KW  - Interferons: metabolism
KW  - NF-kappa B: genetics
KW  - Neutrophils: metabolism
KW  - Signal Transduction
KW  - COVID-19 (Other)
KW  - cell deconvolution (Other)
KW  - disease modeling (Other)
KW  - disease recovery (Other)
KW  - gene regulation (Other)
KW  - immunology (Other)
KW  - medicine (Other)
KW  - systems biology (Other)
KW  - viral infection (Other)
KW  - NF-kappa B (NLM Chemicals)
KW  - Interferons (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9110324
C6  - pmid:35675822
DO  - DOI:10.1016/j.xcrm.2022.100652
UR  - https://pub.dzne.de/record/164649
ER  -