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Статья
A time-resolved proteomic and diagnostic map characterizes COVID-19 disease progression and predicts outcome
V. Demichev,
P. Tober-Lau,
T. Nazarenko,
C. Thibeault,
H. Whitwell,
O. Lemke,
A. Röhl,
A. Freiwald,
L. Szyrwiel,
D. Ludwig,
C. Correia-Melo,
E. Helbig,
P. Stubbemann,
N. Grüning,
O. Blyuss,
S. Vernardis,
M. White,
C. Messner,
M. Joannidis,
T. Sonnweber,
S. Klein,
A. Pizzini,
Y. Wohlfarter,
S. Sahanic,
R. Hilbe,
B. Schaefer,
S. Wagner,
M. Mittermaier,
F. Machleidt,
C. Garcia,
C. Ruwwe-Glösenkamp,
T. Lingscheid,
L. de Jarcy,
M. Stegemann,
M. Pfeiffer,
L. Jürgens,
S. Denker,
D. Zickler,
P. Enghard,
A. Zelezniak,
A. Campbell,
C. Hayward,
D. Porteous,
R. Marioni,
A. Uhrig,
H. Müller-Redetzky,
H. Zoller,
J. Löffler-Ragg,
M. Keller,
I. Tancevski,
J. Timms,
A. Zaikin,
S. Hippenstiel,
M. Ramharter,
M. Witzenrath,
N. Suttorp,
K. Lilley,
M. Mülleder,
L. Sander,
M. Ralser,
F. Kurth,
2020
Abstract COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There is an urgent need for predictive markers that can guide clinical decision-making, inform about the effect of experimental therapies, and point to novel therapeutic targets. Here, we characterize the time-dependent progression of COVID-19 through different stages of the disease, by measuring 86 accredited diagnostic parameters and plasma proteomes at 687 sampling points, in a cohort of 139 patients during hospitalization. We report that the time-resolved patient molecular phenotypes reflect an initial spike in the systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution and immunomodulation. Further, we show that the early host response is predictive for the disease trajectory and gives rise to proteomic and diagnostic marker signatures that classify the need for supplemental oxygen therapy and mechanical ventilation, and that predict the time to recovery of mildly ill patients. In severely ill patients, the molecular phenotype of the early host response predicts survival, in two independent cohorts and weeks before outcome. We also identify age-specific molecular response to COVID-19, which involves increased inflammation and lipoprotein dysregulation in older patients. Our study provides a deep and time resolved molecular characterization of COVID-19 disease progression, and reports biomarkers for risk-adapted treatment strategies and molecular disease monitoring. Our study demonstrates accurate prognosis of COVID-19 outcome from proteomic signatures recorded weeks earlier.
Цитирование
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Версии
- 1. Version of Record от 2020-11-12
Метаданные
Об авторах
-
V. Demichev
University of Cambridge; Francis Crick Institute; Charité -
P. Tober-Lau
Charité -
T. Nazarenko
University College London -
C. Thibeault
Charité -
H. Whitwell
Imperial College London -
O. Lemke
Charité -
A. Röhl
Charité -
A. Freiwald
Charité -
L. Szyrwiel
Francis Crick Institute -
D. Ludwig
Charité -
C. Correia-Melo
Francis Crick Institute -
E. Helbig
Charité -
P. Stubbemann
Charité -
N. Grüning
Charité -
O. Blyuss
University of Hertfordshire; I.M. Sechenov First Moscow State Medical University -
S. Vernardis
Francis Crick Institute -
M. White
Francis Crick Institute -
C. Messner
Francis Crick Institute; Charité -
M. Joannidis
Innsbruck Medical University -
T. Sonnweber
Innsbruck Medical University -
S. Klein
Innsbruck Medical University -
A. Pizzini
Innsbruck Medical University -
Y. Wohlfarter
Innsbruck Medical University -
S. Sahanic
Innsbruck Medical University -
R. Hilbe
Innsbruck Medical University -
B. Schaefer
Innsbruck Medical University -
S. Wagner
Innsbruck Medical University -
M. Mittermaier
Charité -
F. Machleidt
Charité -
C. Garcia
Charité -
C. Ruwwe-Glösenkamp
Charité -
T. Lingscheid
Charité -
L. de Jarcy
Charité -
M. Stegemann
Charité -
M. Pfeiffer
Charité -
L. Jürgens
Charité -
S. Denker
Charité -
D. Zickler
Charité -
P. Enghard
Charité -
A. Zelezniak
Francis Crick Institute; Chalmers University of Technology -
A. Campbell
University of Edinburgh -
C. Hayward
University of Edinburgh -
D. Porteous
University of Edinburgh -
R. Marioni
University of Edinburgh -
A. Uhrig
Charité -
H. Müller-Redetzky
Charité -
H. Zoller
Innsbruck Medical University -
J. Löffler-Ragg
Innsbruck Medical University -
M. Keller
Innsbruck Medical University -
I. Tancevski
Innsbruck Medical University -
J. Timms
University College London - A. Zaikin
-
S. Hippenstiel
Charité -
M. Ramharter
Bernhard Nocht Institute for Tropical Medicine -
M. Witzenrath
Charité -
N. Suttorp
Charité -
K. Lilley
University of Cambridge -
M. Mülleder
Charité -
L. Sander
Charité -
M. Ralser
Francis Crick Institute; Charité -
F. Kurth
Charité; Bernhard Nocht Institute for Tropical Medicine
Предметная рубрика
- COVID-19
Тип документа
- preprint
Тип лицензии Creative Commons
- CC BY-NC-ND
Правовой статус документа
- Свободная лицензия
Источник
- lens
