Robust prognostic signatures derived from proteomic panel profiling of plasma from patients with severe COVID-19 complications

Abstract

COVID-19 complications present a huge burden on healthcare systems and warrant a predictive risk model for disease severity of SARS-CoV-2 infection to enable early intervention, prospective decision-making and triaging of patients. We profiled plasma proteins from COVID-19 patients (severe n=50, and mild n=50) and controls (n=50) using function- and pathway-based panels developed with the highly specific proximity extension assays. Several biological pathways were specific for patients with severe complications. Based on these dysregulated profiles, we propose candidate FDA-approved drugs that target multiple upregulated proteins to treat severe complications. In addition, the set of differentially expressed plasma proteins in severe disease contained a robust 46-protein signature, the COVID-19 molecular severity score, which predicts the risk of severe complications. We cross-validated this molecular severity score in an independent cohort and found it useful within three days after hospital admission to predict COVID-19 severity and outcomes. Associated with the molecular severity score, we identified a set of clinical parameters available at admission, that act as a clinical risk score for complications. The molecular and clinical risk scores described in our study may be prognostic tools for severe COVID-19 disease and help alleviate the pressure on healthcare systems during infection peaks.

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus Disease 2019 (COVID- 19), with over 770 million cases and 7 million deaths [1,2]. Severe acute disease is primarily characterised by infection of the respiratory tract and pathological hyper-inflammatory responses, often referred to as a "cytokine storm" that can lead to acute respiratory distress syndrome (ARDS) and ultimately mortality [3][4][5]. Post-acute and chronic sequelae of COVID-19 are now well described, with post-COVID conditions affecting 10-30% of COVID-19 patients [6] and long-COVID at least 10% of patients [7][8][9].…”

“…The inflammatory mediators that are associated with severe COVID-19, as distinct from mild disease, have been the focus of many studies, with such insights having the potential to identify therapeutic anti-disease interventions [3,5,[10][11][12][13][14][15][16][17]. Elevated mRNA or protein levels of a range of cytokines have been identified in peripheral blood of severe COVID-19 patients, these include inter alia IL-6, IL-1, IL-2, IL-17, IL-18, TNF, IFNG and CSF2 (GM-CSF) (ibid).…”