SARS-CoV-2 Protein Deposition Enhances Renal Complement Activation and Aggravates Kidney Injury in Membranous Nephropathy After COVID-19

SARS-CoV-2 蛋白沉积增强肾脏补体活化并加重 COVID-19 后膜性肾病的肾脏损伤

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作者:Guoqin Wang, Lei Yang, Xiaoyi Xu, Weiyi Guo, Lijun Sun, Yanyan Wang, Wenrong Cheng, Nan Ye, Lingqiang Kong, Xiaoyi Zhao, Hong Cheng

Conclusion

Excessive activation of the complement system aggravated symptoms in MN after COVID-19. Therapeutic strategy targeting the complement system may need to be considered.

Methods

A total of 38 patients with biopsy-proven MN who developed new-onset proteinuria after COVID-19 were enrolled in this study. One hundred patients with primary MN diagnosed before the COVID-19 pandemic were the control. Renal immunohistochemical staining for SARS-CoV-2 nucleocapsid protein was performed in 38 patients with MN after COVID-19. Serum membrane attack complex (MAC) was detected by enzyme-linked immunosorbent assay. Glomerular staining for the complement proteins in different pathways were detected by immunohistochemistry.

Results

Thirteen of 38 patients had positive staining for SARS-CoV-2 nucleocapsid protein. Compared with the control patients, the clinical manifestations were more severe in patients after COVID-19. Patients with positive SARS-CoV-2 staining had a higher proportion of nephrotic syndrome, lower level of serum albumin, and greater severity of renal interstitial fibrosis than those of patients with negative SARS-CoV-2 staining. Serum MAC level and renal MAC staining intensity of MN after COVID-19 were significantly higher than those of the control patients. MAC expression in MN patients with positive SARS-CoV-2 staining was stronger than that in both control patients and MN after COVID-19 with negative SARS-CoV-2 staining. The expression trend of factor H was consistent with that of MAC.

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