Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19
Authors
Yapeng Su, Institute for Systems Biology, Seattle, WA, 98109, USA;
Daniel Chen, Institute for Systems Biology, Seattle, WA, 98109, USA;
Dan Yuan, Institute for Systems BiologyFollow
Christopher Lausted, Institute for Systems Biology, Seattle, WA, 98109, USA;
Jongchan Choi, Institute for Systems Biology, Seattle, WA, 98109, USA;
Chengzhen L Dai, Institute for Systems Biology, Seattle, WAFollow
Valentin Voillet
Venkata R Duvvuri, Institute for Systems BiologyFollow
Kelsey Scherler, Institute for Systems Biology, Seattle, WA 98109, USAFollow
Pamela Troisch, Institute for Systems Biology, Seattle, WA, 98109, USA;
Priyanka Baloni, Institute for Systems Biology, Seattle WA 98109.Follow
Guangrong Qin, Institute for Systems Biology, Seattle, WA, 98109, USA;
Brett Smith, Institute for Systems BiologyFollow
Sergey A Kornilov, Institute for Systems Biology, Seattle, WAFollow
Clifford Rostomily, Institute for Systems BiologyFollow
Alex Xu, Institute for Systems Biology, Seattle, WA, 98109, USA;
Jing Li
Shen Dong
Alissa Rothchild
Jing Zhou
Kim Murray, Institute for Systems Biology, Seattle, WA, 98109, USA;
Rick Edmark, Institute for Systems Biology, Seattle, WA, 98109, USA;
Sunga Hong, Institute for Systems Biology, Seattle, WA, 98109, USA;
John Heath, Institute for Systems Biology, Seattle, WA, 98109, USA;
John Earls, Institute for Systems Biology, Seattle, WA, 98109, USA;
Rongyu Zhang, Institute for Systems Biology, Seattle, WA, 98109, USA;
Jingyi Xie, Institute for Systems Biology, Seattle, WA, 98109, USA;
Sarah Li, Institute for Systems Biology, Seattle, WA, 98109, USA;
Ryan Roper, Institute for Systems BiologyFollow
Lesley Jones, Institute for Systems Biology, Seattle, WA, 98109, USA;
Yong Zhou, Institute for Systems Biology, Seattle, WA, 98109, USAFollow
Lee Rowen, Institute for Systems Biology, Seattle, WA, 98109, USA;
Rachel Liu, Institute for Systems Biology, Seattle, WA, 98109, USA;
Sean Mackay
D Shane O'Mahony, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;Follow
chris dale, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;Follow
Julie A Wallick, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;Follow
Heather A Algren, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;Follow
Zager A. Michael
ISB-Swedish COVID19 Biobanking Unit
Wei Wei, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Nathan D Price, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Sui Huang, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Naeha Subramanian, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Kai Wang, Institute for Systems Biology, Seattle, WA, 98109, USA;
Andrew T Magis, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Jennifer Hadlock, Institute for Systems Biology, Seattle, WA, 98109, USA;
Leroy Hood, Institute for Systems Biology, Seattle, WA, 98109, USA;Follow
Alan Aderem
Jeffrey A. Bluestone
Lewis L. Lanier
Philip D. Greenberg
Raphael Gottardo
Mark M. Davis
Jason D Goldman, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USA;Follow
James R. Heath, Institute for Systems Biology, Seattle, WA, 98109, USA;
Publication Date
10-22-2020
Abstract
Highlights
- • Analysis of serial blood from 139 COVID-19 patients reveals immune coordination
- • A major immunological shift is seen between mild and moderate infection
- • Moderate and severe cases exhibit inflammation and a sharp drop in blood nutrients
- • Novel immune cell subsets emerge in moderate cases and increase with severity
Summary
We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.
Specialty/Research Institute
Infectious Diseases
Specialty/Research Institute
Institute for Systems Biology
