Assessment of Humoral Response at SARS-CoV‑2 Infection by Multipronged Functional Proteomics Approaches

In the past decade, a major goal in biomedical research has been to understand why individuals differ in disease susceptibility, disease dynamics, and progression. In many pathologies, this variability stems from evolved immune mechanisms that resist inflammatory stress from various diseases that have been encountered throughout life. These may provide advantages against other diseases, reduce comorbidities, and enhance longevity. This study evaluates prior immunity as a prognostic factor in COVID-19 patients, crucial for understanding plasmatic signaling cascades in different disease stages and their impact on disease progression. COVID-19, caused by SARS-CoV-2, primarily affects the respiratory system and presents a wide range of symptoms, posing significant challenges to medicine. This study systematically analyzed prior immunity and inflammation in two independent cohorts of infected patients. A serological profile is determined by protein microarrays, which identify IgM and IgG responses against 37 prevalent microbial pathogens and provide a comprehensive plasma analysis of 21 acute-phase proteins. Our results reveal distinct serological profiles correlating with disease severity, indicating that immune system dysregulation in COVID-19 patients is linked to existing immunity. These findings highlight the relevance of prior immunity for monitoring disease progression, particularly in infections and vaccine failure, and underscore the importance of functional proteomics in determining prognostic biomarkers.