Abstract
SummaryWe 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.
Highlights
The novel coronavirus disease, COVID-19, has rapidly spread to become a global health challenge, with over 38 million cases and over 1 million associated fatalities as reported through midOctober 2020. 20%–31% of symptomatic patients require hospitalization, with intensive care unit (ICU) admission rates ranging from 4.9%–11.5%, and fatality rates ranging from 2%–10%
Studies on peripheral blood mononuclear cells (PBMCs) using single-cell analytics, have revealed phenomena that tracked with disease severity, including robust HLA class II downregulation on monocytes (Wilk et al, 2020), lymphopenia (Cao, 2020), immune cell exhaustion (Zheng et al, 2020), and elevated levels of inflammatory cytokines (Del Valle et al, 2020)
Lucas et al (2020) reported on maladapted cytokine profiles associated with severe COVID-19, including immune dysregulation arising from impaired type I interferon (IFN) response associated with elevated interleukin (IL)-6 (Hadjadj et al, 2020)
Summary
The novel coronavirus disease, COVID-19, has rapidly spread to become a global health challenge, with over 38 million cases and over 1 million associated fatalities as reported through midOctober 2020. 20%–31% of symptomatic patients require hospitalization, with intensive care unit (ICU) admission rates ranging from 4.9%–11.5%, and fatality rates ranging from 2%–10% (Iype1480 Cell 183, 1479–1495, December 10, 2020(legend continued on page)Article ll and Gulati, 2020). Most reports on immune dysfunction in COVID-19 patients have focused on severe disease. Studies on peripheral blood mononuclear cells (PBMCs) using single-cell analytics, have revealed phenomena that tracked with disease severity, including robust HLA class II downregulation on monocytes (Wilk et al, 2020), lymphopenia (Cao, 2020), immune cell exhaustion (Zheng et al, 2020), and elevated levels of inflammatory cytokines (Del Valle et al, 2020). Inflammation and immune activation are expected to accompany a viral infection, but understanding the coupling between elevated inflammation signals, plasma metabolite composition, and immune cell dysfunction requires a full characterization of both plasma and PBMCs in large cohorts of COVID19 patients representing the spectrum of infection severities
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