Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients

Abstract

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host’s innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.

Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study—The COViNEPH Project

“…In a randomized phase 1/2 clinical trial with Valneva, antigen-specific interferon-γ T-cells reactive were observed against the spike, membrane, and nucleocapsid proteins [21]. Of course, take into account the fact that not all viral epitopes of the virus need to be immunogenic [23]. Research in this area is currently underway.…”

Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein

“…There was no corresponding neutralizing effect using antisera that recognized the C terminal region of SARS-CoV-1 ORF3a in two separate studies [61,62] after 2-4 days of infection. Previous studies have also revealed a significant proportion of convalescent sera or plasma of patients with ORF3a antibodies compared to patients who had succumbed to SARS-CoV infection [60,63]. This would support further exploration of the therapeutic potential of ORF3a antibodies.…”

Serological evaluation of patients with coronavirus disease-2019 in Daegu, South Korea

“…In the recent studies about association between prognosis of COVID-19 and anti-SARS-CoV-2 antibody titer, non-structural protein targeted IgM antibodies were associated with a good prognosis and structural protein, including N protein, targeted IgG antibodies were associated with high mortality [ 22 ]. Although the kit we used measured structural protein targeted total antibodies including IgG, there was no significant difference in anti-SARS-CoV-2 antibody between patients who died and those who recovered from COVID-19.…”

“…good prognosis and structural protein, including N protein, targeted IgG antibodies were associated with high mortality [22]. Although the kit we used measured structural protein targeted total antibodies including IgG, there was no significant difference in anti-SARS-CoV-2 antibody between patients who died and those who recovered from COVID-19.…”