RESUMO
BackgroundEstimating the response of different cohorts (e.g. vaccinated or critically ill) to new SARS-CoV-2 variants is important to customize measures of control. Thus, our goal was to evaluate binding of antibodies from sera of infected and vaccinated people to different antigens expressed by SARS-CoV-2 variants. MethodsWe compared sera from vaccinated donors with sera from four patient/donor cohorts: critically ill patients admitted to an intensive care unit (split in sera collected between 2 and 7 days after admission and more than ten days later), a NIBSC/WHO reference panel of SARS-CoV-2 positive individuals, and ambulatory or hospitalized (but not critically ill) positive donors. Samples were tested with an anti-SARS-CoV-2 IgG serological assay designed with microplates coated with a SARS-CoV-2 RBD recombinant antigen. The same sample sets were also tested with microplates coated with antigens harbouring RBD mutations present in eleven of the most widespread variants. ResultsSera from vaccinated individuals exhibited higher antibody binding (P<0.001) than sera from infected (but not critically ill) individuals when tested against the WT and each of 11 variants RBD. The optical density generated by sera from non-critically ill convalescence individuals upon binding to variants antigens was different (P<0.05) from that of the WT in some variants--noteworthy, Beta, Gamma, Delta, and Delta Plus variants. ConclusionsUnderstanding differences in binding and neutralizing antibody titers against WT vs variant RBD antigens from different donor cohorts can help design variant-specific immunoassays and complement other diagnostic and clinical data to evaluate the epidemiology of new variants.
RESUMO
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has become a global crisis. To gain systems-level insights into its pathogenesis, we compared the blood proteome and phosphoproteome of ICU patients with or without SARS-CoV-2 infection, and healthy control subjects by quantitative mass spectrometry. We find that COVID-19 is marked with hyperactive T cell and B cell signaling, compromised innate immune response, and dysregulated inflammation, coagulation, metabolism, RNA splicing, transcription and translation pathways. SARS-CoV-2 infection causes global reprogramming of the kinome and kinase-substrate network, resulting in defective antiviral defense via the CK2-OPN-IL-12/IFN-/{beta} axis, lymphocyte cell death via aberrant JAK/STAT signaling, and inactivation of innate immune cells via inhibitory SIRPA, SIGLEC and SLAM family receptor signaling. Our work identifies CK2, SYK, JAK3, TYK2 and IL-12 as potential targets for immunomodulatory treatment of severe COVID-19 and provides a valuable approach and resource for deciphering the mechanism of pathogen-host interactions.
