Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19
Abstract Background Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Critical Care |
| Online Access: | https://doi.org/10.1186/s13054-022-04153-3 |
| _version_ | 1828110825773072384 |
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| author | Katherine D. Wick Aleksandra Leligdowicz Andrew Willmore Sidney A. Carrillo Rajani Ghale Alejandra Jauregui Suzanna S. Chak Viet Nguyen Deanna Lee Chayse Jones Robin Dewar H. Clifford Lane Kirsten N. Kangelaris Carolyn M. Hendrickson Kathleen D. Liu Pratik Sinha David J. Erle Charles R. Langelier Matthew F. Krummell Prescott G. Woodruff Carolyn S. Calfee Michael A. Matthay the COMET Consortium |
| author_facet | Katherine D. Wick Aleksandra Leligdowicz Andrew Willmore Sidney A. Carrillo Rajani Ghale Alejandra Jauregui Suzanna S. Chak Viet Nguyen Deanna Lee Chayse Jones Robin Dewar H. Clifford Lane Kirsten N. Kangelaris Carolyn M. Hendrickson Kathleen D. Liu Pratik Sinha David J. Erle Charles R. Langelier Matthew F. Krummell Prescott G. Woodruff Carolyn S. Calfee Michael A. Matthay the COMET Consortium |
| author_sort | Katherine D. Wick |
| collection | DOAJ |
| description | Abstract Background Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. Methods SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived “high antigen” cutoff of N-antigen ≥ 1000 pg/mL was also tested. Results N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03–1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. Conclusions Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease. |
| first_indexed | 2024-04-11T11:25:23Z |
| format | Article |
| id | doaj.art-e599ea26c99e4e01a0e78f4b33fff553 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-11T11:25:23Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-e599ea26c99e4e01a0e78f4b33fff5532022-12-22T04:26:20ZengBMCCritical Care1364-85352022-09-0126111110.1186/s13054-022-04153-3Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19Katherine D. Wick0Aleksandra Leligdowicz1Andrew Willmore2Sidney A. Carrillo3Rajani Ghale4Alejandra Jauregui5Suzanna S. Chak6Viet Nguyen7Deanna Lee8Chayse Jones9Robin Dewar10H. Clifford Lane11Kirsten N. Kangelaris12Carolyn M. Hendrickson13Kathleen D. Liu14Pratik Sinha15David J. Erle16Charles R. Langelier17Matthew F. Krummell18Prescott G. Woodruff19Carolyn S. Calfee20Michael A. Matthay21the COMET ConsortiumCardiovascular Research Institute, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San FranciscoVirus Isolation and Serology Laboratory, Applied and Developmental Directorate, Frederick National LaboratoryDivision of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Hospital Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San FranciscoDivision of Nephrology, Department of Medicine, University of California San Francisco School of MedicineDepartment of Anesthesia, Division of Critical Care, Washington UniversityCardiovascular Research Institute, University of California San FranciscoDivision of Infectious Diseases, University of California San FranciscoImmunoX Initiative, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoCardiovascular Research Institute, University of California San FranciscoAbstract Background Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. Methods SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived “high antigen” cutoff of N-antigen ≥ 1000 pg/mL was also tested. Results N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03–1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. Conclusions Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.https://doi.org/10.1186/s13054-022-04153-3 |
| spellingShingle | Katherine D. Wick Aleksandra Leligdowicz Andrew Willmore Sidney A. Carrillo Rajani Ghale Alejandra Jauregui Suzanna S. Chak Viet Nguyen Deanna Lee Chayse Jones Robin Dewar H. Clifford Lane Kirsten N. Kangelaris Carolyn M. Hendrickson Kathleen D. Liu Pratik Sinha David J. Erle Charles R. Langelier Matthew F. Krummell Prescott G. Woodruff Carolyn S. Calfee Michael A. Matthay the COMET Consortium Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 Critical Care |
| title | Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 |
| title_full | Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 |
| title_fullStr | Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 |
| title_full_unstemmed | Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 |
| title_short | Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19 |
| title_sort | plasma sars cov 2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized covid 19 |
| url | https://doi.org/10.1186/s13054-022-04153-3 |
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