Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection

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

doi:10.1016/j.gastha.2021.12.009

Validation of the Performance of A1HPV6, a Triage Blood Test for the Early Diagnosis and Prognosis of SARS-CoV-2 Infection

Gastro Hep Adv. 2022;1(3):393-402. doi: 10.1016/j.gastha.2021.12.009. Epub 2022 Feb 7.

Authors

Pauline Maisonnasse¹, Thierry Poynard², Mehdi Sakka³, Sepideh Akhavan⁴, Romain Marlin¹, Valentina Peta^{2

5}, Olivier Deckmyn⁵, Nesrine Braham Ghedira³, Yen Ngo⁵, Marika Rudler⁶, Sylvie van der Werf^{7

8}, Stephane Marot⁴, Dominique Thabut⁶, Harry Sokol⁹, Chantal Housset², Alain Combes¹⁰, Roger Le Grand¹, Patrice Cacoub¹¹

Affiliations

¹ Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
² Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France.
³ Department of Metabolic Biochemistry, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, France.
⁴ Department of Virology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, France.
⁵ BioPredictive, Research, Paris, France.
⁶ Department of Hepatology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, France.
⁷ Department of Virology, CNRS UMR 3569, Institut Pasteur, Paris, France.
⁸ National Reference Center for Respiratory Viruses, Institut Pasteur, Paris, France.
⁹ Gastroenterology Department, INSERM, Centre de Recherche Saint Antoine, Sorbonne Université, Paris, France.
¹⁰ Department of Intensive Care Unit, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, France.
¹¹ Department of Internal Medicine and Clinical Immunology, AP-HP Pitié-Salpêtrière, Sorbonne Université, Paris, France.

Abstract

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.

Keywords: A1, Apolipoprotein A1; A2M, alpha2-macroglobulin; ALT, alanine aminotransferase; Apolipoprotein A1; COVID-19; Dpi, days after infection; GGT, gamma glutamyl transpeptidase; HDL-C, high-density lipoprotein cholesterol; HP, haptoglobin; Haptoglobin; ICU, intensive care unit; NHP, non-human primate model; Nonhuman Primate Model; SAA, serum amyloid A.

Associated data

ClinicalTrials.gov/NCT01927133