Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand.
Int J Infect Dis. 2021 Nov;112:227-234. doi: 10.1016/j.ijid.2021.09.021. Epub 2021 Sep 15.
As coronavirus disease 2019 (COVID-19) rages on worldwide, there is an urgent need to characterize immune correlates of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify immune determinants of COVID-19 severity.
This study examined the longitudinal profiles of neutralizing antibody (NAb) titers in hospitalized COVID-19 patients clinically diagnosed with mild symptoms, pneumonia, or severe pneumonia, up to 12 months after illness onset, using live-virus neutralization. Multiplex, correlation, and network analyses were used to characterize serum-derived inflammatory cytokine profiles in all severity groups.
Peak NAb titers correlated with disease severity, and NAb titers declined over the course of 12 months regardless of severity. Multiplex analyses revealed that IP-10, IL-6, IL-7, and VEGF-α were significantly elevated in severe pneumonia cases compared to those with mild symptoms and pneumonia cases. Correlation and network analyses further suggested that cytokine network formation was distinct in different COVID-19 severity groups.
The study findings inform on the long-term kinetics of naturally acquired serological immunity against SARS-CoV-2 and highlight the importance of identifying key cytokine networks for potential therapeutic immunomodulation.
随着 2019 年冠状病毒病(COVID-19)在全球肆虐,人们迫切需要描述严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染的保护免疫相关性,并确定 COVID-19 严重程度的免疫决定因素。
本研究使用活病毒中和试验,检测了临床诊断为轻症、肺炎或重症肺炎的住院 COVID-19 患者在发病后 12 个月内中和抗体(NAb)滴度的纵向特征。采用多重、相关和网络分析方法,对所有严重程度组的血清衍生炎症细胞因子谱进行了特征描述。
峰值 NAb 滴度与疾病严重程度相关,无论严重程度如何,NAb 滴度在 12 个月内均呈下降趋势。多重分析显示,与轻症和肺炎患者相比,重症肺炎患者的 IP-10、IL-6、IL-7 和 VEGF-α 显著升高。相关和网络分析进一步表明,不同 COVID-19 严重程度组的细胞因子网络形成存在明显差异。
该研究结果阐明了针对 SARS-CoV-2 的自然获得性血清免疫的长期动力学,并强调了确定潜在治疗性免疫调节关键细胞因子网络的重要性。