Jing Xixi, Xu Min, Song Deye, Yue Tingting, Wang Yali, Zhang Pan, Zhong Yanjun, Zhang Min, Lam Tommy Tsan-Yuk, Faria Nuno Rodrigues, De Clercq Erik, Li Guangdi
Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, 410078, China.
Department of Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Immun Ageing. 2022 Mar 5;19(1):12. doi: 10.1186/s12979-022-00271-2.
COVID-19 patients may experience "cytokine storm" when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies.
This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization.
At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients.
Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.
当人体免疫系统产生过量细胞因子/趋化因子时，新型冠状病毒肺炎（COVID-19）患者可能会经历“细胞因子风暴”。然而，尚不清楚炎性细胞因子的早期反应是否会导致抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗体的高滴度或低滴度。
这项回顾性研究纳入了一组272例实验室确诊的SARS-CoV-2住院患者。在住院期间对血清细胞因子（白细胞介素-2受体（IL-2R）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α））、抗SARS-CoV-2 IgG/IgM抗体和外周血生物标志物进行实验室评估。
入院时，36.4%的患者病情严重，51.5%的患者年龄≥65岁，60.3%的患者有合并症。在老年患者（≥65岁）中观察到较高水平的IL-2R和IL-6。在中度和重度患者之间观察到IL-2R（症状出现后第2周与≥第5周）、IL-6（第1周与≥第5周）、IL-8（第2周与≥第5周）和IL-10（第1周与第3周）存在显著差异。重度患者的抗SARS-CoV-2 IgG滴度显著高于中度患者，但IgM未观察到这种差异。早期IL-6、IL-8和TNF-α（症状出现后≤2周）的高滴度与晚期IgG（症状出现后≥5周）的高滴度呈正相关。死亡大多发生在老年重症患者（45.9%）中。生存分析显示，患者年龄、基线COVID-19严重程度和基线IL-6是影响生存时间的危险因素，尤其是在老年重症患者中。
IL-6等细胞因子升高的早期反应反映了活跃的免疫反应，导致针对COVID-19的IgG抗体高滴度。
