Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, Madrid, Spain.
Instituto Sanitario Princesa, Madrid, Spain.
Front Immunol. 2022 Mar 23;13:836516. doi: 10.3389/fimmu.2022.836516. eCollection 2022.
COVID-19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.
We analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein.
We found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms.
These findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.
COVID-19 可引起广泛的严重程度和症状。许多研究分析了严重程度的决定因素,但没有分析某些类型的症状。更重要的是,很少有研究分析了接触大量病毒但仍未感染的患者。
我们分析了两个高病毒暴露风险队列中的 ACE2、血管紧张素 II 和抗刺突抗体的血清水平,分别是高风险的卫生保健工作者或与感染密切亲属共同生活的高暴露但未感染的人群,以及有症状的血清阳性患者。我们测试了这些个体血清中和带有刺突蛋白的慢病毒假型的能力。
我们发现,高暴露但未感染的个体的 ACE2 血清水平显著升高。此外,来自这些血清阴性个体的血清可以在细胞检测中更强烈地中和 SARS-CoV-2 感染,尽管它们没有抗-CoV-2 IgG 抗体,这表明血清中高水平的 ACE2 可能在不产生常规抗体反应的情况下在一定程度上防止了主动感染。最后,我们发现,在有症状的患者中,与呼吸道症状相比,发生皮肤症状的感染患者的 ACE2 水平显著升高,并且 ACE2 在症状较轻的患者中也较高。
这些发现表明,可溶性 ACE2 可用作预测 SARS-CoV-2 感染风险和区分 COVID-19 疾病亚型的潜在生物标志物。