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

Journal Article (Journal Article)

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 + IgG + 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 source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19-vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2-specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines.

Full Text

Duke Authors

Cited Authors

  • Haddad, NS; Nguyen, DC; Kuruvilla, ME; Morrison-Porter, A; Anam, F; Cashman, KS; Ramonell, RP; Kyu, S; Saini, AS; Cabrera-Mora, M; Derrico, A; Alter, D; Roback, JD; Horwath, M; O'Keefe, JB; Wu, HM; Wong, A-KI; Dretler, AW; Gripaldo, R; Lane, AN; Wu, H; Chu, HY; Lee, S; Hernandez, M; Engineer, V; Varghese, J; Patel, R; Jalal, A; French, V; Guysenov, I; Lane, CE; Mengistsu, T; Normile, KE; Mnzava, O; Le, S; Sanz, I; Daiss, JL; Lee, FE-H

Published Date

  • May 17, 2021

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • 322 - 335

PubMed ID

  • 34001652

Electronic International Standard Serial Number (EISSN)

  • 2573-7732

Digital Object Identifier (DOI)

  • 10.4049/immunohorizons.2100011


  • eng

Conference Location

  • United States