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

Introduction: COVID-19 has been reported to be associated with the occurrence and recurrence of membranous nephropathy (MN). The clinicopathological characteristics and complement system activation of MN after COVID-19 are unclear.

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.

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.