Profiling of the antibody response to viral and bacterial antigens and its correlations with time-to-hospital discharge: Covacta and Mariposa study

Abstract

Abstract In this study the role of the humoral response to viral and bacterial antigens in hospitalised patients with severe COVID-19 and its association with clinical endpoint time-to-hospital discharge (TTHD) was investigated. Here, we analysed the antibody (Ab) response to SARS-CoV-2 structural and non structural proteins, other influenza(s) and bacterial proteins using bead-based protein and peptide arrays comprising different viral epitopes. In total, 459 pre-treatment serum samples from hospitalised COVID-19 patients enrolled in the COVACTA and MARIPOSA clinical trials were analysed to identify Ab reactivity to protein antigens and linear epitopes associated with TTHD. Overall we found that most patients had IgG-Abs to SARS-CoV-2 S protein (89%), N protein (90%) and RBD domain (95%). Three major epitopes of the S protein were identified which map to the C-terminus of the RBD, TMPRSS2 cleavage site and fusion peptide 1, and close to the heptad repeat 2 domain. These epitopes could be further researched to understand the immunity to COVID-19 and how it affects outcomes. Abs binding to several peptides mapping to the RBD C-terminus and N-terminal to heptad repeat 2 were associated with longer TTHD. Abs to an epitope mapping to the intracellular domain of S protein and to the RNA-binding domain of the N protein showed the strongest association with longer TTHD. Abs to seasonal corona viruses and influenza A & B, S. aureus, and rhinovirus were associated with shorter TTHD. To conclude, epitope-specific multiplexed Ab profiling of anti-SARS-CoV-2 response may potentially be used to predict clinical outcome. Pre-existing humoral immunity to seasonal corona viruses and influenza may also confer some protective effects against COVID-19