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.

Antibodies against Spike protein correlate with broad autoantigen recognition 8 months post SARS-CoV-2 exposure, and anti-calprotectin autoantibodies associated with better clinical outcomes

“…The magnitude of antibody responses to SARS-CoV-2 have been shown to correlate with COVID-19 disease severity, where higher antibody responses develop during acute disease in more severe cases ( 13 , 15 ). Here, we correlated the anti-SARS-CoV-2 responses with the autoantigen responses and identified a range of degrees of correlation, with the majority showing weak to moderate positive correlations.…”

“…Antibody responses to the Spike, S1, RBD and Nucleoprotein of SARS-CoV-2 have been shown to last up to a year post disease ( 9 – 12 ). In the initial months post infection, studies report the antibody responses to multiple SARS-CoV-2 antigens ( 13 , 14 ), however, less is known about the pattern of persistence to multiple antigens, within the same individuals, post 6 months. During the acute phase of infection, the level of antibody responses has been reported to be associated with disease severity, where those with more severe disease had greater antibody levels ( 13 , 15 ).…”

“…In the initial months post infection, studies report the antibody responses to multiple SARS-CoV-2 antigens ( 13 , 14 ), however, less is known about the pattern of persistence to multiple antigens, within the same individuals, post 6 months. During the acute phase of infection, the level of antibody responses has been reported to be associated with disease severity, where those with more severe disease had greater antibody levels ( 13 , 15 ). Contradictory evidence exists on their persistence, with this association reported by some ( 16 – 18 ), but not all ( 19 , 20 ) studies to continue post-disease.…”

HERV-W ENV antigenemia and correlation of increased anti-SARS-CoV-2 immunoglobulin levels with post-COVID-19 symptoms

“…Both anti-spike and anti-nucleocapsid IgE antibodies were significantly increased when compared to pre-pandemic controls (p<0.01 and p<0.0001, respectively; Figure 2D ). These results highlight that a subgroup of post-COVID-19 condition patients present a sustained immune response against SARS-CoV-2 antigens, with IgG, IgA and IgE levels similar or even increased when compared to those observed during active COVID-19 infections ( 23 , 24 ).…”

“…On another end, the study of antibody response to SARS-CoV-2 by screening virus antigen microarrays revealed that early IgA and IgG responses can constitute markers of acute disease severity ( 23 ). In addition, it was found that SARS-CoV-2 elicits IgE responses with levels positively correlating with severity thus suggesting a link between SARS-CoV-2 infection, degree of severity with mast cell activation ( 23 , 24 ).…”