Humoral Response Profile in SARS-CoV-2 Infection: Differences across Virus Strains and Influenza

The clinical manifestation of COVID-19 after SARS-CoV-2 infection varies greatly, with many patients requiring intensive care due to complications like acute respiratory distress syndrome, reduced respiratory system compliance, and altered iron metabolism, which can be mistaken for worsening Influenza A infection. This highlights the need to study the humoral immune response to better understand the pathophysiology of viral respiratory infections and improve treatments and diagnostics. This study analyzed autoantibody and acute-phase reactant profiles in patients infected with SARS-CoV-2 and Influenza A using customized protein microarrays for sensitive and reproducible results. The findings revealed a significant increase in autoantibodies in SARS-CoV-2 patients, including those targeting calcitonin-related polypeptides, hepatocyte growth factor, or interleukin 8, compared to Influenza A patients, who showed elevated levels of selectin E and surfactant protein D. Additionally, most acute-phase reactants were higher in SARS-CoV-2 patients. The serological profile showed that the wild-type SARS-CoV-2 strain induced both IgM and IgG responses to all viral proteins, while other strains triggered an IgG response only at a later stage. Multiomics factor analysis identified key factors driving variation in COVID-19's heterogeneous disease presentation. These insights offer valuable information for developing vaccines and therapeutic strategies against SARS-CoV-2.