期刊
MSPHERE
卷 6, 期 2, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/mSphere.00203-21
关键词
SARS-CoV-2; coronaviruses; epitope mapping; phage display; prognostic
类别
资金
- UCI COVID-19 Basic, Translational and Clinical Research Fund (CRAFT)
- Allergan Foundation
- UCOP Emergency COVID-19 Research Seed Funding
- Public Impact Fellowship from the UCI Graduate Division
- National Science Foundation Graduate Research Fellowship Program [DGE-1839285]
- NIH [GM-69337]
- National Center for Research Resources
- National Center for Advancing Translational Sciences from the NIH [TR001414]
- ETR - Chao Family NCI-Comprehensive Cancer Center Support Grant from the NCI [P30CA062203]
This study identified antibody epitopes associated with severe COVID-19 outcomes and introduced a disease risk factor score for early identification and triage of high-risk patients, showing a 96.7% specificity in predicting severe disease outcomes. This information could guide more effective therapeutic intervention for COVID-19 patients.
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.
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