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COVID-19 Multiomic Immune Response Study Reveals Differences in Disease Progression, Severity

NEW YORK – A team led by researchers at the Institute for Systems Biology has completed a large multiomic study characterizing the immune response in COVID-19.

Detailed in a paper published this week in Cell, the effort used bulk proteome and metabolome measurements along with single-cell transcriptomic and proteomic assays in 265 samples from 139 COVID-19 patients as well as samples from 268 healthy subjects to investigate the immune response to SARS-CoV-2 infection and how it relates to disease progression and severity.

One of the main findings was that patients' immune profiles differed significantly between mild and moderate disease, while the profiles of patients with moderate and severe infections were more similar. The researchers also found that patients with mild disease more closely resembled healthy subjects in many respects than they did patients with moderate or severe disease.

The researchers generated a vast quantity of omics data at both the bulk and single-cell level. Using Olink Proteomics proximity extension assays they measured the levels of 464 proteins in patient plasma. Metabolomics firm Metabolon made mass spec-based measurements of 1,050 metabolites in plasma. At the single-cell level, the researchers used IsoPlexis's cytokine profiling assay to measure cytokine production of peripheral blood mononuclear cells along with 10X Genomics' Chromium Single Cell Kits to collect transcriptomic, surface protein level, and TCR and BCR sequence information.

The researchers ran these analysis on two blood draws from the COVID-19 patients, one collected shortly after the initial diagnosis and the other several days later.

Using this data, the researchers constructed what they called a "severity-dependent cross-omic correlation network" highlighting relationships between different omics data and disease severity. Among the findings was that increasing disease severity appeared to be linked to elevated levels of inflammation along with the depletion of lipid levels in patient plasma and that this shift was particularly pronounced in mild versus moderate cases while moderate and severe cases exhibited more similar multi-omic profiles. This shift from mild to moderate and severe infection was characterized, they wrote, "by the preferential loss of lipids, amino acids and xenobiotic metabolism and significant elevation of inflammatory cytokines."

The researchers similarly found a sharp change in immune cell repertoires between mild and moderate or severe cases, with increasing disease severity linked to an increase in the levels of activated adaptive immune cells and the appearance of new immune cell phenotypes including a proliferative-exhausted phenotype in CD8 and CD4 T cells as well as the appearance of novel innate immune cells.

The authors suggested that their findings could provide insight into tools for treating COVID-19 patients such as anti-inflammatory therapies and added that the shift in immune profile between patients with mild and moderate forms of the disease indicate that therapeutic intervention at the moderate stage could prove most effective.