Serum IgG anti-SARS-CoV-2 Binding Antibody Level Is Strongly Associated With IgA and Functional Antibody Levels in Adults Infected With SARS-CoV-2

Abstract

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China, and then rapidly spread causing an unprecedented pandemic. A robust serological assay is needed to evaluate vaccine candidates and better understand the epidemiology of coronavirus disease (COVID-19).MethodsWe used the full-length spike (S) protein of SARS-CoV-2 for the development of qualitative and quantitative IgG and IgA anti-S enzyme linked immunosorbent assays (ELISA). A total of 320 sera used for assay development were comprised of pandemic sera from SARS-CoV-2 infected adults (n=51) and pre-pandemic sera (n=269) including sera from endemic human coronavirus infected adults. Reverse cumulative curves and diagnostic test statistics were evaluated to define the optimal serum dilution and OD cutoff value for IgG anti-S and IgA anti-S ELISAs. The IgG and IgA anti-S, and three functional antibodies (ACE-2 receptor blocking antibody, lentipseudovirus-S neutralizing antibody, and SARS-CoV-2 neutralizing antibody) were measured using additional SARS-CoV-2 PCR positive sera (n=76) and surveillance sera (n=25). Lastly, the IgG and IgA anti-S levels were compared in different demographic groups.ResultsThe optimal serum dilution for the qualitative IgG anti-S ELISA was at 1:1024 yielding a 99.6% specificity, 92.2% sensitivity, 92.9% positive predictive value (PPV), and 99.6% negative predictive value (NPV) at a SARS-CoV-2 seroprevalence of 5%. The optimal serum dilution for the qualitative IgA anti-S ELISA was at 1:128 yielding a 98.9% specificity, 76.5% sensitivity, 78.3% PPV, and 98.8% NPV at the same seroprevalence. Significant correlations were demonstrated between the IgG and IgA (r=0.833 for concentrations, r=0.840 for titers) as well as between IgG and three functional antibodies (r=0.811-0.924 for concentrations, r=0.795-0.917 for titers). The IgG and IgA anti-S levels were significantly higher in males than females (p<0.05), and in adults with moderate/severe symptoms than in adults with mild/moderate symptoms (p<0.001).ConclusionWe developed a highly specific and sensitive IgG anti-S ELISA assay to SARS-CoV-2 using full length S protein. The IgG anti-S antibody level was strongly associated with IgA and functional antibody levels in adults with SARS-CoV-2 infection. Gender and disease severity, rather than age, play an important role in antibody levels.

Plasma biomarkers for systemic inflammation in COVID‐19 survivors

“…Previous studies reported that the virus‐specific immunoglobulin G (IgG) levels in COVID‐19 patients significantly increased and associated with disease severity during the acute phase of SARS‐CoV‐2 infection [ 22 , 23 ]. It is unclear, however, if the development of PASC correlates with the levels of IgG in COVID‐19 survivors.…”

Development of a colloidal gold-based immunochromatographic assay for rapid detection of nasal mucosal secretory IgA against SARS-CoV-2

“…Antibody assays are valuable tools for determining population seroprevalence, diagnosing past infections, studying antibody responses elicited by virus infections, evaluating vaccine immunogenicity, and establishing immune correlates of protection (Ye et al, 2021). The outcomes of these assays can help assess population vulnerability and identify individuals at risk of reinfection.…”

Role of the humoral immune response during COVID-19: guilty or not guilty?

“…Indeed, many studies have reported that specific antibody titers (even for antibodies directed against non-structural proteins and accessory proteins) are higher in patients with moderate/severe disease than in patients with asymptomatic/mild disease over the course of the infection 7 – 17 . Antibody levels are also higher in men than in women 8 , 18 , 19 , an observation that can be accounted for by the higher levels of ACE2 expression in men than in women 20 , rendering men more susceptible than women to SARS-CoV-2 infection. Similar differences between the sexes have been reported for other viruses, including MERS, SARS-CoV, Epstein Barr virus, HBV, HCV, and West Nile virus 21 .…”