Systematic evaluation of plasma signaling cascades by functional proteomics approaches: SARS-CoV-2 infection as model.

PURPOSE: Acute phase reactants (APRs) play a critical role in inflammation. The difference in their physiological functions or the different dynamic ranges of these proteins in plasma makes it difficult to detect them simultaneously and to use several of these proteins as a tool in clinical practice. EXPERIMENTAL DESIGN: A novel multiplex assay has been designed and optimized to carry out a high-throughput and simultaneous screening of APRs, allowing the detection of each of them at the same time and in their corresponding dynamic range. RESULTS: Using Sars-CoV-2 infection as a model, it has been possible to profile different patterns of acute phase proteins that vary significantly between healthy and infected patients. In addition, severity profiles (acute respiratory distress syndrome and sepsis) have been established. CONCLUSIONS AND CLINICAL RELEVANCE: Differential profiles in acute phase proteins can serve as a diagnostic and prognostic tool, among patient stratification. The design of this new platform for their simultaneous detection paves the way for them to be more extensive use in clinical practice.

SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS.

Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which is one of the major complications in COVID-19 patients. Dysregulation of the immune system and imbalances in cytokine release and immune cell activation are involved in SARS-CoV-2 infection. Here, the inflammatory, antigen, and auto-immune profile of patients presenting COVID-19-associated severe ARDS has been analyzed using functional proteomics approaches. Both, innate and humoral responses have been characterized through acute-phase protein network and auto-antibody signature. Severity and sepsis by SARS-CoV-2 emerged to be correlated with auto-immune profiles of patients and define their clinical progression, which could provide novel perspectives in therapeutics development and biomarkers of COVID-19 patients. Humoral response in COVID-19 patients' profile separates with significant differences patients with or without ARDS. Furthermore, we found that this profile can be correlated with COVID-19 severity and results more common in elderly patients.