Viral Evolution and Transmission Unit, IRCCS Ospedale San Raffaele, Milan, Italy.
Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
Nat Commun. 2021 May 11;12(1):2670. doi: 10.1038/s41467-021-22958-8.
Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.
了解感染过程中针对 SARS-CoV-2 的抗体反应如何演变,可能为 COVID-19 的治疗方法和疫苗接种提供重要的见解。在这里,我们对 COVID-BioB 队列中 162 名有症状的 COVID-19 患者的抗体反应进行了分析,这些患者从症状出现开始进行了长达 8 个月的纵向随访,以发现针对 SARS-CoV-2 的中和抗体,以及识别 SARS-CoV-2 刺突抗原和核蛋白的抗体,或针对季节性β冠状病毒 S2 抗原和 H1N1 流感病毒血凝素的抗体。症状出现后第一周内存在中和抗体与拭子转阴时间相关(p=0.002),而缺乏中和能力与致命结局的风险增加相关(p=0.008)。中和抗体滴度在 5-8 周后逐渐下降,但在大多数康复患者中仍可检测到 8 个月,无论年龄或合并症如何,针对刺突抗原的 IgG 提供了中和的最佳相关性。针对季节性冠状病毒的抗体反应暂时增强,并与针对 SARS-CoV-2 的反应平行,而不会抑制特异性反应或加重疾病进展。因此,我们的结果表明,对 SARS-CoV-2 刺突的免疫反应受损是重症 COVID-19 患者的主要特征,并为 COVID-19 患者的护理和治疗优先级规划提供了信息。