학술논문

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19
Document Type
article
Source
Cell. 183(6)
Subject
Infectious Diseases
Clinical Research
Prevention
Inflammatory and immune system
Good Health and Well Being
Adolescent
Adult
Aged
Aged
80 and over
COVID-19
Female
Genomics
Humans
Male
Middle Aged
RNA-Seq
SARS-CoV-2
Severity of Illness Index
Single-Cell Analysis
ISB-Swedish COVID19 Biobanking Unit
CITE-seq
immune response
infection
metabolomics
multi-omics
proteomics
single-cell RNA-seq
single-cell TCR-seq
single-cell secretome
Biological Sciences
Medical and Health Sciences
Developmental Biology
Language
Abstract
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.