Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection

Haddad, N. S.; Nguyen, D. C.; Kuruvilla, M. E.; Morrison-Porter, A.; Anam, F.; Cashman, K. S.; Ramonell, R. P.; Kyu, S.; Saini, A. S.; Cabrera-Mora, M.; Derrico, A.; Alter, D.; Roback, J. D.; Horwath, M.; O'Keefe, J. B.; Wu, H. M.; Wong, A.-K. I.; Dretler, A. W.; Gripaldo, R.; Lane, A. N.; Wu, H.; Lee, S.; Hernandez, M.; Engineer, V.; Varghese, J.; Le, S.; Sanz, I.; Daiss, J. L.; Lee, F. E.-H.

doi:10.1101/2020.12.04.410589

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bioRxiv · 10.1101/2020.12.04.410589

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection

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Abstract

BackgroundSARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses. A multi-antigen immunoassay to define the complex serological landscape and clinical associations is essential. MethodsWe developed a multiplex immunoassay and evaluated serum/plasma from adults with RT-PCR-confirmed SARS-CoV-2 infections during acute illness (N=52) and convalescence (N=69); and pre-pandemic (N=106) and post-pandemic (N=137) healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 Nucleocapsid (N), Spike domain 1 (S1), receptor binding domain (S1-RBD) and S1-N-terminal domain (S1-NTD). ResultsTo diagnose infection, the combined [IgA+IgG+IgM] or IgG for N, S1, and S1-RBD yielded AUC values -0.90 by ROC curves. From days 6-30 post-symptom onset, the levels of antigen-specific IgG, IgA or [IgA+IgG+IgM] were higher in patients with severe/critical compared to mild/moderate infections. Consistent with excessive concentrations of antibodies, a strong prozone effect was observed in sera from severe/critical patients. Notably, mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared to severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 months. ConclusionThis SARS-CoV-2 multiplex immunoassay measures the magnitude, complexity and kinetics of the antibody response against multiple viral antigens. The IgG and combined-isotype SARS-CoV-2 multiplex assay is highly diagnostic of acute and convalescent disease and may prognosticate severity early in illness. One Sentence SummaryIn contrast to patients with moderate infections, those with severe COVID-19 develop prominent, early antibody responses to S1 and N proteins.

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Haddad, N. S., Nguyen, D. C., Kuruvilla, M. E., Morrison-Porter, A., Anam, F., Cashman, K. S., Ramonell, R. P., Kyu, S., Saini, A. S., Cabrera-Mora, M., Derrico, A., Alter, D., Roback, J. D., Horwath, M., O'Keefe, J. B., Wu, H. M., Wong, A.-K. I., Dretler, A. W., Gripaldo, R., Lane, A. N., Wu, H., Lee, S., Hernandez, M., Engineer, V., Varghese, J., Le, S., Sanz, I., Daiss, J. L., Lee, F. E.-H.. 2020-12-06. Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection. https://doi.org/10.1101/2020.12.04.410589

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