Beijing You'an Hospital, Capital Medical University, China.
Wellcome Centre for Human Genetics.
JCI Insight. 2020 Jul 9;5(13):139834. doi: 10.1172/jci.insight.139834.
Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks.
A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay.
We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases.
Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.
确定 COVID-19 疾病严重程度的免疫相关性是临床管理、疫苗评估和药物开发的迫切需要。在这里，我们展示了对来自住院 COVID-19 患者的血液中关键免疫介质、细胞因子和趋化因子的时间分析，这些患者在 4 周的时间内进行了连续采样和随访。
共有 71 名在中国北京佑安医院确诊的 COVID-19 住院患者（轻度 53 例，重度 18 例）和 18 名健康志愿者入组，每例患者每月每 4-7 天通过生物素化多重免疫分析测量外周血中的 34 种免疫介质、细胞因子和趋化因子。
我们发现趋化因子 RANTES（CCL5）在轻症患者中从感染的早期开始就显著升高，但在重症患者中则不然。我们还发现早期产生的抑制性介质，包括 IL-10 和 IL-1RA，与疾病严重程度显著相关，并且在第 1 周时 CCL5、IL-1 受体拮抗剂（IL-1RA）和 IL-10 的组合可能预测患者的预后。大多数与病毒感染中的细胞因子风暴相关的细胞因子，如 IL-6 和 IFN-γ，仅在重症 COVID-19 疾病的晚期才显著升高。TNF-α和 GM-CSF 在重症和轻症病例之间没有显著差异。
综上所述，我们的数据表明，早期增加 CCL5 的表达可能有助于预防患者发展为重症疾病。我们的数据还表明，单独和组合测量血液中 CCL5 以及 IL-1RA 和 IL-10 的水平可能是有用的预后生物标志物，可指导治疗策略。
