A specific molecular signature in SARS-CoV-2–infected kidney biopsies

International audience; Acute kidney injury (AKI) is one of the most important complications in COVID-19 patients and is considered a negativeprognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and itscontribution to the renal deterioration process, remains a controversial issue. By studying 32 renal biopsies from COVID-19 patients we confirmed that the major pathological feature of COVID-19 is acute tubular injury (ATI). Using smFISH, weshowed that the SARS-CoV-2 infects living renal cells and that infection, which parallels renal ACE2 expression levels, isassociated to increase death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures inSARS-CoV-2 infected kidneys as compared to healthy kidneys and non-COVID-19 ATI kidneys. On the other hand, wedemonstrated that SARS-CoV-2 and Hantavirus, two RNA viruses, activated different genetic networks despite theytriggered the same pathological lesions. Finally, we identified XAF1 as a critical target of SARS-CoV-2 infection. Inconclusion, this study demonstrates that SARS-CoV2 can directly infect living renal cells and identified specific druggablemolecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function inseverely affected COVID-19 patients.