Maisonnasse Pauline, Poynard Thierry, Sakka Mehdi, Akhavan Sepideh, Marlin Romain, Peta Valentina, Deckmyn Olivier, Ghedira Nesrine Braham, Ngo Yen, Rudler Marika, van der Werf Sylvie, Marot Stephane, Thabut Dominique, Sokol Harry, Housset Chantal, Combes Alain, Le Grand Roger, Cacoub Patrice
Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.
Assistance Publique-Hôpitaux de Paris (AP-HP), INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Sorbonne Université, Paris, France.
Gastro Hep Adv. 2022;1(3):393-402. doi: 10.1016/j.gastha.2021.12.009. Epub 2022 Feb 7.
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.
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.
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; = .80), like for sensitivity 92% (85-96) vs 94% (88-97; = .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 ( < .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 ( < .01) and increased at D14 ( < .01) but was still lower than controls; HP increased at D2 and remained elevated at D14.
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.
载脂蛋白A1（A1）和触珠蛋白（HP）的血清水平与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的传播及严重程度相关。我们构建并验证了一个整合A1、HP、α2-巨球蛋白和γ-谷氨酰转移酶的多变量风险计算器（A1HPV6），以提高病毒学生物标志物的性能。
在一项对非重症SARS-CoV-2感染住院患者的前瞻性观察研究中，在127例患者中构建了A1HPV6，并在116例患者中进行了验证。在代表普通人群的7482名对照中评估了其特异性。主要诊断终点是SARS-CoV-2 PCR检测呈阳性患者的受试者操作特征曲线下面积。主要预后终点是A1HPV6经年龄和性别调整后预测世界卫生组织（WHO）分期>4期（W>4）严重程度患者的风险。我们在非人灵长类动物模型（NHP）中评估了从基线到SARS-CoV-2感染后7天（D7）A1HPV6各成分的动力学变化。
在验证亚组中，A1HPV6的受试者操作特征曲线下面积为0.99（95%CI 0.97-0.99），与构建亚组中的0.99（0.99-0.99；P = 0.80）无显著差异，敏感性分别为92%（85-96）和94%（88-97；P = 0.29）。A1HPV6与W>4相关，优势比为1.3（1.1-1.5；P = 0.002）。在NHP中，A1水平在D2时下降（P<0.01），并在D4时恢复正常；HP水平在D2时升高，并在D4时达到峰值。在患者中与对照相比，A1浓度在D2时非常低（P<0.01），并在D14时升高（P<0.01），但仍低于对照；HP在D2时升高，并在D14时仍保持升高。
这些结果验证了A1HPV6的诊断和预后性能。在NHP模型中观察到了载脂蛋白A1、HP和α2-巨球蛋白相似的动力学变化。ClinicalTrials.gov编号，NCT01927133。
