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 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.
Significance statement 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.
Competing Interest Statement
The authors declare the following competing financial interest(s): P.L.F., R.N., and A.J. have a financial interest in a company, Nanommune Inc., that is commercializing the COVAM technology. Nanommune partners with Sino Biological Inc. (Beijing, China) for expression and purification of COVAM antigens used in this study. The terms of this arrangement have been reviewed and approved by the University of California, Irvine in accordance with its conflict of interest policies.
Footnotes
Preprint Information: Preprint can be found on bioRxiv with DOI: https://doi.org/10.1101/2020.10.15.341743. Version 1 was made available October 16, 2020. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Abbreviations
- COVID-19
- Coronavirus disease 2019
- ELISA
- enzyme-linked immunosorbent assay
- COVAM
- coronavirus antigen microarray
- Ep9
- epitope 9
- ICU
- intensive care unit
- SARS-CoV-2
- severe acute respiratory syndrome coronavirus
- SARS-CoV-1
- severe acute respiratory syndrome
- MERS
- Middle East respiratory syndrome
- AST
- aspartate aminotransferase
- IL-6
- interleukin 6
- IL-10
- interleukin 10
- Abs
- antibodies
- S protein
- SARS-CoV-2 spike glycoprotein
- N protein
- SARS-CoV-2 nucleocapsid protein
- M protein
- SARS-CoV-2 membrane protein
- E protein
- SARS-CoV-2 envelope protein
- Phage ELISA
- ELISA with phage-displayed epitopes
- PCR
- polymerase chain reaction
- QC ELISA
- quality control ELISA
- PDB
- protein data bank
- HKU-1
- human coronavirus HKU1
- NL63
- human coronavirus NL63
- IgG
- immunoglobulin G
- IgM
- immunoglobulin M
- αEp9 Abs
- anti-Ep9 antibodies
- ANOVA
- analysis of variance
- DRFS
- disease risk factor score