Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection
Background and Aims: Apolipoprotein A1 (A1) and haptoglobin (HP) serum levels are associated with the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have constructed and validated a multivariable risk calculator (A1HPV6) integrating A1, HP, alpha2-m...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Gastro Hep Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572322000061 |
| _version_ | 1828780292215668736 |
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| author | Pauline Maisonnasse Thierry Poynard Mehdi Sakka Sepideh Akhavan Romain Marlin Valentina Peta Olivier Deckmyn Nesrine Braham Ghedira Yen Ngo Marika Rudler Sylvie van der Werf Stephane Marot Dominique Thabut Harry Sokol Chantal Housset Alain Combes Roger Le Grand Patrice Cacoub |
| author_facet | Pauline Maisonnasse Thierry Poynard Mehdi Sakka Sepideh Akhavan Romain Marlin Valentina Peta Olivier Deckmyn Nesrine Braham Ghedira Yen Ngo Marika Rudler Sylvie van der Werf Stephane Marot Dominique Thabut Harry Sokol Chantal Housset Alain Combes Roger Le Grand Patrice Cacoub |
| author_sort | Pauline Maisonnasse |
| collection | DOAJ |
| description | Background and Aims: Apolipoprotein A1 (A1) and haptoglobin (HP) serum levels are associated with the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have constructed and validated a multivariable risk calculator (A1HPV6) integrating A1, HP, alpha2-macroglobulin, and gamma glutamyl transferase to improve the performances of virological biomarkers. Methods: In a prospective observational study of hospitalized patients with nonsevere SARS-CoV-2 infection, A1HPV6 was constructed in 127 patients and validated in 116. The specificity was assessed in 7482 controls representing the general population. The primary diagnostic endpoint was the area under the receiver operating characteristic curve in patients with positive SARS-CoV-2 PCR. The primary prognostic endpoint was the age-and-sex adjusted risk of A1HPV6 to predict patients with WHO-stage > 4 (W > 4) severity. We assessed the kinetics of the A1HPV6 components in a nonhuman primate model (NHP), from baseline to 7 days (D7) after SARS-CoV-2 infection. Results: The area under the receiver operating characteristic curve for A1HPV6 was 0.99 (95% CI 0.97–0.99) in the validation subset, which was not significantly different from that in the construction subset, 0.99 (0.99–0.99; P = .80), like for sensitivity 92% (85–96) vs 94% (88–97; P = .29). A1HPV6 was associated with W > 4, with a significant odds ratio of 1.3 (1.1–1.5; 0.002). In NHP, A1 levels decreased (P < .01) at D2 and normalized at D4; HP levels increased at D2 and peaked at D4. In patients, A1 concentration was very low at D2 vs controls (P < .01) and increased at D14 (P < .01) but was still lower than controls; HP increased at D2 and remained elevated at D14. Conclusion: These results validate the diagnostic and prognostic performances of A1HPV6. Similar kinetics of apolipoprotein A1, HP, and alpha-2-macroglobulin were observed in the NHP model. ClinicalTrials.gov number, NCT01927133. |
| first_indexed | 2024-12-11T17:15:50Z |
| format | Article |
| id | doaj.art-d512ccbd6fe74ee2be66d77c0226a4b7 |
| institution | Directory Open Access Journal |
| issn | 2772-5723 |
| language | English |
| last_indexed | 2024-12-11T17:15:50Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj.art-d512ccbd6fe74ee2be66d77c0226a4b72022-12-22T00:57:21ZengElsevierGastro Hep Advances2772-57232022-01-0113393402Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 InfectionPauline Maisonnasse0Thierry Poynard1Mehdi Sakka2Sepideh Akhavan3Romain Marlin4Valentina Peta5Olivier Deckmyn6Nesrine Braham Ghedira7Yen Ngo8Marika Rudler9Sylvie van der Werf10Stephane Marot11Dominique Thabut12Harry Sokol13Chantal Housset14Alain Combes15Roger Le Grand16Patrice Cacoub17Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France; Correspondence: Address correspondence to: Thierry Poynard, MD, PhD, Hepatology Groupe Hospitalier Pitie-Salpêtrière, 57 Bd Hôpital, Paris 75013, France.Department of Metabolic Biochemistry, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceDepartment of Virology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France; BioPredictive, Research, Paris, FranceBioPredictive, Research, Paris, FranceDepartment of Metabolic Biochemistry, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceBioPredictive, Research, Paris, FranceDepartment of Hepatology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceDepartment of Virology, CNRS UMR 3569, Institut Pasteur, Paris, France; National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, FranceDepartment of Virology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceDepartment of Hepatology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceGastroenterology Department, INSERM, Centre de Recherche Saint Antoine, Sorbonne Université, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, FranceDepartment of Intensive Care Unit, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceCenter for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, FranceDepartment of Internal Medicine and Clinical Immunology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, FranceBackground and Aims: Apolipoprotein A1 (A1) and haptoglobin (HP) serum levels are associated with the spread and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We have constructed and validated a multivariable risk calculator (A1HPV6) integrating A1, HP, alpha2-macroglobulin, and gamma glutamyl transferase to improve the performances of virological biomarkers. Methods: In a prospective observational study of hospitalized patients with nonsevere SARS-CoV-2 infection, A1HPV6 was constructed in 127 patients and validated in 116. The specificity was assessed in 7482 controls representing the general population. The primary diagnostic endpoint was the area under the receiver operating characteristic curve in patients with positive SARS-CoV-2 PCR. The primary prognostic endpoint was the age-and-sex adjusted risk of A1HPV6 to predict patients with WHO-stage > 4 (W > 4) severity. We assessed the kinetics of the A1HPV6 components in a nonhuman primate model (NHP), from baseline to 7 days (D7) after SARS-CoV-2 infection. Results: The area under the receiver operating characteristic curve for A1HPV6 was 0.99 (95% CI 0.97–0.99) in the validation subset, which was not significantly different from that in the construction subset, 0.99 (0.99–0.99; P = .80), like for sensitivity 92% (85–96) vs 94% (88–97; P = .29). A1HPV6 was associated with W > 4, with a significant odds ratio of 1.3 (1.1–1.5; 0.002). In NHP, A1 levels decreased (P < .01) at D2 and normalized at D4; HP levels increased at D2 and peaked at D4. In patients, A1 concentration was very low at D2 vs controls (P < .01) and increased at D14 (P < .01) but was still lower than controls; HP increased at D2 and remained elevated at D14. Conclusion: These results validate the diagnostic and prognostic performances of A1HPV6. Similar kinetics of apolipoprotein A1, HP, and alpha-2-macroglobulin were observed in the NHP model. ClinicalTrials.gov number, NCT01927133.http://www.sciencedirect.com/science/article/pii/S2772572322000061COVID-19Nonhuman Primate ModelApolipoprotein A1Haptoglobin |
| spellingShingle | Pauline Maisonnasse Thierry Poynard Mehdi Sakka Sepideh Akhavan Romain Marlin Valentina Peta Olivier Deckmyn Nesrine Braham Ghedira Yen Ngo Marika Rudler Sylvie van der Werf Stephane Marot Dominique Thabut Harry Sokol Chantal Housset Alain Combes Roger Le Grand Patrice Cacoub Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection Gastro Hep Advances COVID-19 Nonhuman Primate Model Apolipoprotein A1 Haptoglobin |
| title | Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection |
| title_full | Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection |
| title_fullStr | Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection |
| title_full_unstemmed | Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection |
| title_short | Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection |
| title_sort | validation of the performance of a1hpv6 a triage blood test for the early diagnosis and prognosis of sars cov 2 infection |
| topic | COVID-19 Nonhuman Primate Model Apolipoprotein A1 Haptoglobin |
| url | http://www.sciencedirect.com/science/article/pii/S2772572322000061 |
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