tetano
Editor, Senior Moderator
mSphere
. 2021 Apr 28;6(2):e00203-21.
doi: 10.1128/mSphere.00203-21.
Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score
Sanjana R Sen[SUP] #[/SUP][SUP] 1 [/SUP], Emily C Sanders[SUP] #[/SUP][SUP] 2 [/SUP], Kristin N Gabriel[SUP] #[/SUP][SUP] 1 [/SUP], Brian M Miller[SUP] 2 [/SUP], Hariny M Isoda[SUP] 2 [/SUP], Gabriela S Salcedo[SUP] 2 [/SUP], Jason E Garrido[SUP] 1 [/SUP], Rebekah P Dyer[SUP] 1 [/SUP], Rie Nakajima[SUP] 3 [/SUP], Aarti Jain[SUP] 3 [/SUP], Ana-Maria Caldaruse[SUP] 4 [/SUP], Alicia M Santos[SUP] 2 [/SUP], Keertna Bhuvan[SUP] 2 [/SUP], Delia F Tifrea[SUP] 5 [/SUP], Joni L Ricks-Oddie[SUP] 6 7 [/SUP], Philip L Felgner[SUP] 3 [/SUP], Robert A Edwards[SUP] 5 [/SUP], Sudipta Majumdar[SUP] 2 [/SUP], Gregory A Weiss[SUP] 8 2 4 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; coronaviruses; epitope mapping; phage display; prognostic.
. 2021 Apr 28;6(2):e00203-21.
doi: 10.1128/mSphere.00203-21.
Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score
Sanjana R Sen[SUP] #[/SUP][SUP] 1 [/SUP], Emily C Sanders[SUP] #[/SUP][SUP] 2 [/SUP], Kristin N Gabriel[SUP] #[/SUP][SUP] 1 [/SUP], Brian M Miller[SUP] 2 [/SUP], Hariny M Isoda[SUP] 2 [/SUP], Gabriela S Salcedo[SUP] 2 [/SUP], Jason E Garrido[SUP] 1 [/SUP], Rebekah P Dyer[SUP] 1 [/SUP], Rie Nakajima[SUP] 3 [/SUP], Aarti Jain[SUP] 3 [/SUP], Ana-Maria Caldaruse[SUP] 4 [/SUP], Alicia M Santos[SUP] 2 [/SUP], Keertna Bhuvan[SUP] 2 [/SUP], Delia F Tifrea[SUP] 5 [/SUP], Joni L Ricks-Oddie[SUP] 6 7 [/SUP], Philip L Felgner[SUP] 3 [/SUP], Robert A Edwards[SUP] 5 [/SUP], Sudipta Majumdar[SUP] 2 [/SUP], Gregory A Weiss[SUP] 8 2 4 [/SUP]
Affiliations
- PMID: 33910993
- DOI: 10.1128/mSphere.00203-21
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.
Keywords: SARS-CoV-2; coronaviruses; epitope mapping; phage display; prognostic.