Background: Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at tissue level. The mechanisms and pathways of local complement activation remain unclear. Methods: We performed immunofluorescence analyses of autopsy specimens of lungs, kidney and liver from nine COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG and spike protein of SARS-CoV-2. Findings: Lung deposits of C1q, C4, C3 and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. Factor B deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on hepatic artery and portal vein of the liver. Interpretation. Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease.

中文翻译：

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COVID-19 患者的多器官补体沉积

背景：据报道，COVID-19 患者的循环补体激活产物水平升高，但关于组织水平补体受累的信息有限。局部补体激活的机制和途径仍不清楚。方法：我们对 9 名死于急性呼吸衰竭的 COVID-19 患者的肺、肾和肝的尸检标本进行了免疫荧光分析。嵌入 OCT 的速冻样品用针对补体成分和激活产物、IgG 和 SARS-CoV-2 刺突蛋白的抗体染色。结果：C1q、C4、C3 和 C5b-9 的肺沉积物位于肺泡间隔的毛细血管和肺泡细胞上。IgG 表现出类似的均匀分布，表明经典途径激活。刺突蛋白是 IgG 的潜在靶点，但其分布不均表明其他病毒和组织分子可能是 IgG 的靶点。在 COVID-19 肺部也发现了因子 B 沉积物，这与替代途径的激活一致，而 MBL 和 MASP-2 几乎无法检测到。对肾脏和肝脏标本的分析反映了在肺中观察到的发现。在肾小管和血管上观察到补体沉积，在肾小球和肝动脉和门静脉中只有轻微的 C5b-9 染色。解释。由激活经典和替代途径引起的已故 COVID-19 患者不同器官中的补体沉积支持该疾病的多器官性质。在 COVID-19 肺部也发现了因子 B 沉积物，这与替代途径的激活一致，而 MBL 和 MASP-2 几乎无法检测到。对肾脏和肝脏标本的分析反映了在肺中观察到的发现。在肾小管和血管上观察到补体沉积，在肾小球和肝动脉和门静脉中只有轻微的 C5b-9 染色。解释。由激活经典和替代途径引起的已故 COVID-19 患者不同器官中的补体沉积支持该疾病的多器官性质。在 COVID-19 肺部也发现了因子 B 沉积物，这与替代途径的激活一致，而 MBL 和 MASP-2 几乎无法检测到。对肾脏和肝脏标本的分析反映了在肺中观察到的发现。在肾小管和血管上观察到补体沉积，在肾小球和肝动脉和门静脉中只有轻微的 C5b-9 染色。解释。由激活经典和替代途径引起的已故 COVID-19 患者不同器官中的补体沉积支持该疾病的多器官性质。在肾小管和血管上观察到补体沉积，在肾小球和肝动脉和门静脉中只有轻微的 C5b-9 染色。解释。由激活经典和替代途径引起的已故 COVID-19 患者不同器官中的补体沉积支持该疾病的多器官性质。在肾小管和血管上观察到补体沉积，在肾小球和肝动脉和门静脉中只有轻微的 C5b-9 染色。解释。由激活经典和替代途径引起的已故 COVID-19 患者不同器官中的补体沉积支持该疾病的多器官性质。