Frequency of IgE antibody response to SARS-CoV-2 RBD protein across different disease severity COVID19 groups

Abstract

Background: COVID-19 appears to have a progression of three stages. The latter stage is characterized by a high level of cytokine release, which in turn triggers an uncontrolled reaction known as cytokine storm where mast cells are involved. The presence of anti-IgE antibodies against SARS-CoV-2 in this phase has been previously reported, suggesting an association with the severity of the disease. Our study aims to assess the prognostic significance of IgE antibodies against SARS-CoV-2 across a spectrum of clinical presentations, including individual with mild symptoms, hospitalized patients, and those who presented a critical progression.

Methods: The study included 64 patients distributed into the following groups: 22 critically ill hospitalized individuals (Critical); 21 non-critical hospitalized patients (Severe); 21 mild symptomatic non-hospitalized cases (Mild); and 22 healthy blood donors with samples collected in October 2019. Anti-IgE antibodies against Spike (S) protein were detected using a homemade ELISA, where the plate was sensitized with the RBD of recombinant S protein.

Results: Among 64 SARS-CoV-2 infected patients, 28.1% tested positive for IgE isotype antibodies against S protein RBD, whose prevalence was similar across severity groups: Mild 23.8%, Severe 28.6%, and Critical 31.8% (p = 0.842). Patients with IgE response exhibited higher levels of LDH compared to non-IgE responders, with a 40% increase (p = 0.037), and a non-significantly higher tendency in other inflammatory markers.

Conclusion: In SARS-CoV-2 infection, roughly a fourth of patients presented an IgE isotype response, regardless of disease severity, which is associated with higher levels of LDH.

Keywords: Antibody response; IgE; Prognostic factor; S protein; SARS-CoV-2.

Fig. 1

Anti-RBD IgE antibody titers quantified using an in-house ELISA. Boxplots illustrate the distribution of peptide quantification. Whiskers extend 1.5 times the interquartile range (IQR) from each end of the box. Point-range symbols represent the adjusted group means of protein titers after statistical control for confounders, and their extension represents the 95% confidence intervals. These estimates were derived from a linear model and adjusted for sex, age and days from first clinical symptoms to sample extraction, in which Anti-RBD IgE antibody titer quantifications were transformed using the most suitable Box-Cox transformation with a lambda value of 0.25 in order to fulfill model assumptions. The red dashed line represents the threshold for ELISA positivity set to achieve a 95% assay specificity in the group of healthy controls