Profiling systemic inflammation and neutrophil function in hospitalized patients with COVID19: results from PREDICT-COVID19

Abstract

Introduction: COVID19 can cause profound systemic inflammation. Understanding inflammation and immune cell function may allow prediction of outcomes, longer-term effects and identification of further therapeutic targets.

Methods: Prospective observational study of patients with PCR-confirmed SARS-CoV-2 enrolled within 96 hours of admission at two UK hospitals(May2020–March2021), with longitudinal sampling up to 29 days. mRNAseq was performed in peripheral blood cells, 45 serum cytokines were measured with Olink Target48 panel, isolated neutrophils were processed for proteomic and functional analyses. Severe disease was defined as requirement for ventilatory support or death within 28 days of admission.

Results: 176 COVID19 patients were included (mean age 64.9years, SD13.6), 101 were male (57.4%). 56 patients developed severe disease (31.8%), mortality was 16.5%. A subset underwent neutrophil proteomics (n=81). 19 serum cytokines were significantly associated with severity (p<0.05; ROC analysis), CCL7 had the strongest discriminatory value (AUC 0.78, 95%CI 0.70-0.85). There were 317 significant differentially expressed genes (Wald test with Benjanini-Hochberg correction; p<0.05) at baseline comparing those discharged or still hospitalised at 4 weeks; pathways included complement and B cell activation. Neutrophil proteomics showed upregulation of interferon signalling, which decreased over time but was not linked to severity. Cytokine and toll like receptor levels, plus the eosinophil-associated protein PRG2, were associated with disease severity and outcome.

Conclusion: Proteomic and transcriptomic approaches identified changes associated with patient outcomes.