Istituto Auxologico Italiano, IRCCS, Experimental Laboratory of Immuno-rheumatologic Researches, Cusano Milanino, Milan, Italy.
Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.
Autoimmun Rev. 2023 Jan;22(1):103232. doi: 10.1016/j.autrev.2022.103232. Epub 2022 Nov 19.
Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome.
新型冠状病毒病 19（COVID-19）可能表现为一种多器官疾病，除了上呼吸道和下呼吸道受累外，还伴有高度炎症和促血栓形成反应（免疫血栓形成）。先前的数据表明，补体激活在严重形式的免疫血栓形成中起作用。本研究旨在探讨补体是否在疾病的早期阶段参与，并可预测不良结局。我们招募了 97 名因 SARS-CoV-2 阳性 RT-PCR 而出现症状的患者，这些患者因出现呼吸道症状而到急诊室就诊。CT 扫描显示肺部受累轻微的患者出院，其余患者住院治疗。所有患者在 4 周的随访后进行评估，并分为轻症（n=54）、中度（n=17）或重症 COVID-19（n=26）。在开始任何抗炎/免疫抑制治疗之前采集的血液样本，通过 ELISA 检测可溶性 C5b-9（sC5b-9）和 C5a 血浆水平，通过 ELLA 检测以下血清介质：IL-1β、IL-6、IL-8、TNFα、IL-4、IL-10、IL-12p70、IFNγ、IFNα、VEGF-A、VEGF-B、GM-CSF、IL-2、IL-17A、VEGFR2、BLyS。还测量了其他常规实验室参数（纤维蛋白片段 D-二聚体、C 反应蛋白、铁蛋白、白细胞、中性粒细胞、淋巴细胞、单核细胞、血小板、凝血酶原时间、活化部分凝血活酶时间和纤维蛋白原）。还评估了 50 名年龄和性别匹配的健康对照者。与非住院轻症组相比，住院中度和重度患者的 sC5b-9 和 C5a 血浆水平显著升高。sC5b9 和 C5a 血浆水平可预测一个月后疾病的严重程度。IL-6、IL-8、TNFα、IL-10 和补体裂解产物在中度/重度与非住院轻症 COVID-19 患者和健康对照组中均升高，但异质性较大。sC5b-9 和 C5a 血浆水平与 CRP、铁蛋白值和中性粒细胞/淋巴细胞比值呈正相关。补体可在疾病的早期阶段激活，即使在轻度非住院患者中也是如此。即使促炎细胞因子没有增加，也可以观察到补体激活，并且可以预测不良结局。
