One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses

Abstract

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1-receptor binding domain (RBD) and S1-N-terminal domain. For diagnosis, the combined [IgA 1 IgG 1 IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values $0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients-a possible

RETRACTED: Heterogeneous Longitudinal Antibody Responses to Covid-19 mRNA Vaccination

“…21 These results have been confirmed in several independent human studies 22,23 and suggest that recovered survivors of natural infection should be granted the same social/political status of COVID-19 immunity as people who have been fully vaccinated. Additional noteworthy points are that robust immune responses to either SARS-CoV-2 natural infection 24 or the vaccine 21 can be associated with more severe clinical symptoms. Since infection-or vaccine-induced clinical symptoms are partly mediated by cytokine activation, severity of host responses may reflect immune activation and likelihood of future immune protection.…”

Natural killer cell‐mediated ADCC in SARS‐CoV‐2‐infected individuals and vaccine recipients

“…Interestingly, serum samples of vaccinated individuals exceeded results detected in resolvers at higher dilution levels, indicating that previous studies might have underestimated antibody‐mediated functions. A possible explanation is the prozone effect, a phenomenon also known as hook effect, in which high antibody titers interfere with proper antigen–antibody interactions and thus lead to false negative or inaccurately low results in immunoassays [ 32 , 33 , 34 ]. However, the precise functional correlates by which these antibodies mediate their antiviral functions are insufficiently understood.…”

Silent SARS-CoV-2 Infections, Waning Immunity, Serology Testing, and COVID-19 Vaccination: A Perspective

“…But, since IgM class of antibodies has a shorter persistence in relation to IgG, its detection may be used to indicate a recent event (infection or immunization). In the context of SARS-CoV-2 infection or COVID-19 immunization, determining IgM antibodies early in the event (within 2 weeks that may persist up to nearly 3 weeks following disease onset or immunization) and IgG antibodies (beyond 2 weeks until several months after infection or immunization), have been evidently recognized to be more informative for evaluating antibody-based immunological responses with sufficient sensitivity and specificity (31)(32)(33). Interestingly, the beneficial role of IgA, a potent and early SARS-CoV-2-neutralizing agent (34) has been recently documented for intranasal immunization with a Middle East respiratory syndrome coronavirus (MERS)-derived vaccine (35).…”

“…Accordingly, future research studies involving a meticulous analysis of the results reflecting on both S-IgM and S-IgA values and establishing a neutralizing titer like that of the conservative IgG (S-RBD) could be helpful to obtain critical complimentary information. In this connection, it could be worth to consider a combined pan-Ig serological tests hatsimultaneously measures reactive S-IgM (early antibodies), S-IgA (often detectable early antibodies before IgG), and IgG, like these newly developed assays (33,36). In the hindsight, the bigger picture of 'S-pan Ig:neutralization titer' correlation will perhaps broaden the dataset of serological diagnosis and vaccine assessments regarding our understanding of the early phase of immunological response.…”