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

Abstract

Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (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 intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 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 patient's 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.IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

• Authors: Sanjana R 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
• Journal: mSphere (mSphere) Vol. 6 Issue 2 (04 28 2021) ISSN: 2379-5042 [Electronic] United States
• PMID: 33910993 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021 Sen et al.

Chemical References

• Antibodies, Viral
• Coronavirus Nucleocapsid Proteins
• Epitopes
• Phosphoproteins
• nucleocapsid phosphoprotein, SARS-CoV-2

Topics

• Antibodies, Viral (blood)
• COVID-19 (diagnosis, pathology)
• Cell Surface Display Techniques
• Coronavirus Nucleocapsid Proteins (immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes (blood, immunology)
• Humans
• Nucleocapsid (immunology)
• Phosphoproteins (immunology)
• Prognosis
• Risk Factors
• SARS-CoV-2 (immunology)
• Severity of Illness Index