In order to study the mechanisms of COVID-19 damage following the complement activation phase occurring during the innate immune response to SARS-CoV-2, CR1 (the regulating complement activation factor, CD35, the C3b/C4b receptor), C4d deposits on Erythrocytes (E), and the products of complement activation C3b/C3bi, were assessed in 52 COVID-19 patients undergoing O₂ therapy or assisted ventilation in ICU units in Rheims France. An acquired decrease of CR1 density on E from COVID-19 patients was observed (Mean = 418, SD = 162, N = 52) versus healthy individuals (Mean = 592, SD = 287, N = 400), Student’s t-test p < 10⁻⁶, particularly among fatal cases, and in parallel with several parameters of clinical severity. Large deposits of C4d on E in patients were well above values observed in normal individuals, mostly without concomitant C3 deposits, in more than 80% of the patients. This finding is reminiscent of the increased C4d deposits on E previously observed to correlate with sub endothelial pericapillary deposits in organ transplant rejection, and with clinical SLE flares. Conversely, significant C3 deposits on E were only observed among ¼ of the patients. The decrease of CR1/E density, deposits of C4 fragments on E and previously reported detection of virus spikes or C3 on E among COVID-19 patients, suggest that the handling and clearance of immune complex or complement fragment coated cell debris may play an important role in the pathophysiology of SARS-CoV-2. Measurement of C4d deposits on E might represent a surrogate marker for assessing inflammation and complement activation occurring in organ capillaries and CR1/E decrease might represent a cumulative index of complement activation in COVID-19 patients.

Taken together, these original findings highlight the participation of complement regulatory proteins and indicate that E are important in immune pathophysiology of COVID-19 patients. Besides a potential role for monitoring the course of disease, these observations suggest that novel therapies such as the use of CR1, or CR1-like molecules, in order to down regulate complement activation and inflammation, should be considered.

为了研究在对 SARS-CoV-2、CR1（调节补体激活因子，CD35，C3b/C4b 受体）的先天免疫反应期间发生的补体激活阶段后 COVID-19 损伤的机制，C4d 沉积在红细胞上(E) 以及补体激活产物 C3b/C3bi，在法国兰斯的 ICU 病房接受 O ₂治疗或辅助通气的 52 名 COVID-19 患者中进行了评估。与健康个体（平均值 = 592，SD = 287，N = 400）相比，观察到 COVID-19 患者 E 上 CR1 密度的获得性降低（平均值 = 418，SD = 162，N = 52），学生t检验 p < 10 ^-6，特别是在致命病例中，并与临床严重程度的几个参数平行。患者 E 上的大量 C4d 沉积远高于在正常个体中观察到的值，在超过 80% 的患者中，大多数没有伴随的 C3 沉积。这一发现让人想起之前观察到的 E 上增加的 C4d 沉积物与器官移植排斥中的内皮下毛细血管周围沉积物以及临床 SLE 发作相关。相反，仅在 1/4 的患者中观察到 E 上显着的 C3 沉积。CR1/E 密度的降低、E 上 C4 片段的沉积以及先前报告的在 COVID-19 患者中检测到 E 上的病毒尖峰或 C3，表明免疫复合物或补体片段包被的细胞碎片的处理和清除可能在 SARS-CoV-2 的病理生理学中发挥重要作用。E 上 C4d 沉积物的测量可能代表了评估器官毛细血管中发生的炎症和补体激活的替代标志物，而 CR1/E 的降低可能代表了 COVID-19 患者补体激活的累积指数。

总而言之，这些原始发现突出了补体调节蛋白的参与，并表明 E 在 COVID-19 患者的免疫病理生理学中很重要。除了监测疾病进程的潜在作用外，这些观察结果表明，应考虑使用新疗法，例如使用 CR1 或 CR1 样分子，以下调补体激活和炎症。