Molecular Analysis of the Kidney From a Patient With COVID-19–Associated Collapsing Glomerulopathy

Meliambro, Kristin; Li, Xuezhu; Salem, Fadi; Yi, Zhengzi; Sun, Zeguo; Chan, Lili; Chung, Miriam; Chancay, Jorge; Vy, Ha My T.; Nadkarni, Girish; Wong, Jenny S.; Fu, Jia; Lee, Kyung; Zhang, Weijia; He, John C.; Campbell, Kirk N.

Recent Case reports suggest COVID-19 is associated with collapsing glomerulopathy in African Americans with APOL1 risk alleles, however, it is unclear if disease pathogenesis is similar to HIVAN. Here RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19-associated collapsing glomerulopathy and APOL1 risk alleles (G1/G1) revealed similar levels of APOL1 and ACE2 mRNA transcripts as compared to 12 control kidney samples downloaded from the GTEx Portal. Whole genome sequencing of the COVID-19-associated collapsing glomerulopathy kidney sample identified four indel gene variants, three of which are of unknown significance with respect to chronic kidney disease and/or FSGS. Molecular profiling of the kidney demonstrated activation of COVID-19-associated cell injury pathways such as inflammation and coagulation. Evidence for direct SARS-CoV-2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 in both COVID-19-associated collapsing glomerulopathy and HIVAN as compared to control kidney tissue. Importantly, IL-6-induced activation of STAT3 may be a targetable mechanism driving COVID-19-associated acute kidney injury.