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[Preprint]. 2021 Mar 8:2020.10.15.341743. Originally published 2020 Oct 16. [Version 3] doi: 10.1101/2020.10.15.341743

Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

Sanjana Sen, Emily C Sanders, Kristin N Gabriel, Brian M Miller, Hariny M Isoda, Gabriela S Salcedo, Jason E Garrido, Rebekah P Dyer, Rie Nakajima, Aarti Jain, Ana-Maria Caldaruse, Alicia M Santos, Keertna Bhuvan, Delia F Tifrea, Joni L Ricks-Oddie, Philip L Felgner, Robert A Edwards, Sudipta Majumdar, Gregory A Weiss
PMCID: PMC7574261  PMID: 33083803

Abstract

Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the ICU, requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within six days post-symptom onset and sometimes within one day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patients comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 Likelihood Ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention.

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