Université de Paris, Inserm, Paris-Centre de Recherche Cardiovasculaire (PARCC), Paris, France.
Centre d'investigation clinique (CIC1)418 and Département médico-universitaire Cardiologie Rein Transplantation Neurovasculaire (DMU CARTE), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Paris, France.
Clin Infect Dis. 2021 Sep 15;73(6):e1337-e1344. doi: 10.1093/cid/ciab308.
Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized.
In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG).
Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant.
Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.
体液针对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的反应发生在感染 2019 年冠状病毒病(COVID-19)后的第一周内。这些抗体对 SARS-CoV-2 具有中和活性,但其在 COVID-19 后的随时间演变以及对新型变体的效率特征较差。
在这项前瞻性研究中,我们在感染后 3 个月和 6 个月收集了 107 名因 COVID-19 住院患者的血清。我们在评估抗刺突(S)和抗核衣壳(NP)免疫球蛋白 G(IgG)的高通量血清学检测之上进行了定量中和实验。
血清中和抗体效价和 IgG 率随时间推移显著下降。6 个月后,2.8%的患者对 S 和 NP IgG 均呈阴性血清学状态。然而,所有血清对 SARS-CoV-2 均具有持续有效的中和作用。IgG 水平与血清中和相关,且与抗 S 抗体的相关性强于抗 NP 抗体。6 个月时量化的血清中和抗体效价与初始严重程度的标志物相关,尤其是入住重症监护病房和需要机械性有创通气的需求。此外,我们还使用 6 个月采集的血清对多种 SARS-CoV-2 变体进行了检测,发现其对 D614G、B.1.1.7 和 P.1 变体具有有效的中和作用,但对 B.1.351 变体的活性明显减弱。
IgG 率降低和血清学检测结果转为阴性并不意味着中和能力丧失。我们的研究结果表明,至少在 COVID-19 住院患者中,针对原始株以及 D614G、B.1.1.7 和 P.1 变体的体液反应至少在 6 个月内保持持续。然而,针对 B.1.351 变体的保护作用较弱。