Early and Strong Antibody Responses to SARS-CoV-2 Predict Disease Severity in COVID-19 Patients

Abstract

Background Antibody response to SARS-CoV-2 is a valuable biomarker for the assessment of the spread of the virus in a population and evaluation of the vaccine candidates. Recent data suggest that antibody levels also may have a prognostic significance in COVID-19. Most of the serological studies so far rely on testing antibodies against spike (S) or nucleocapsid (N) protein, however antibodies can be directed against other structural and nonstructural proteins of the virus, whereas their frequency, biological and clinical significance is unknown. Methods A novel antigen array comprising 30 SARS-CoV-2 antigens or their fragments was developed and used to examine IgG, IgA, IgE and IgM responses to SARS-CoV-2 in sera from 103 patients with COVID-19 including 34 patients for whom sequential samples were available, and 20 pre-pandemic healthy controls. Results Antibody responses to various antigens are highly correlated and the frequencies and peak levels of antibodies are higher in patients with severe/moderate disease than in those with mild disease. This finding supports the idea that antibodies against SARS-CoV-2 may exacerbate the severity of the disease via antibody-dependent enhancement. Moreover, early IgG and IgA responses to full length S protein may be used as an additional biomarker for the identification of patients who are at risk of developing severe disease. Importantly, this is the first study reporting that SARS-CoV-2 elicits IgE responses and their serum levels positively correlate with the severity of the disease thus suggesting a link between high levels of antibodies and mast cell activation. Conclusions This is the first study assessing the prevalence and dynamics IgG, IgA, IgE and IgM responses to multiple SARS-CoV-2 antigens simultaneously. Results provide important insights into the pathogenesis of COVID-19 and have implications in planning and interpreting antibody-based epidemiological studies.

Impact of vaccination on the presence and severity of symptoms of hospitalised patients with an infection by the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1)

“…Moreover, we included patients from four countries, and our results may have been different if more countries (either European or not) had been represented. In addition, we did not perform anti-Spike serology at admission; anti-Spike antibody level has been shown to be associated with prognosis (Plūme et al 2022; Sanghavi et al 2022), and it might have facilitated understanding of the severity of SARS-CoV-2 infection in some vaccinated subjects, in particular among immunosuppressed subjects who could present lesser response to vaccines. In addition, availability of antiviral treatment was not comparable between the Delta and the Omicron wave, which could have had an impact on mortality.…”

The COVID-19 antibody responses, isotypes and glycosylation: Why SARS-CoV-2 Spike protein complex binding of IgG3 is potentiated in some and immuno-pathologies manifest

“…However, distinguishing and quantitating the various antibody types arising in a patients serum/ plasma sample to a specific antigen by anti-human immunoglobulin chain assays can be expensive in reagent costs, biological sample volumes required and man hours [12].…”

“…prednisolone) showing some benefit [18, 19]. Thus COVID-19 is due to an adverse immune and possibly non-specific response to the SARS-CoV-2 [5,12]. But how and why?…”

“…But how and why? The major features of COVID-19 patients appears to be very high levels of anti-SARS-CoV-2 antibodies in the patients who develop COVID-19 syndrome and not a lack of them [12]. In addition the induction of anti-SARS CoV2 antibodies, by Spike protein mRNA vaccinations is effective in reducing incidence of infection and death from SARS-CoV2 in the global population [20,21].…”