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

Pierre Isnard (1, 2) , Paul Vergnaud (1) , Serge Garbay (1) , Matthieu Jamme (3) , Maeva Eloudzeri (1) , Alexandre Karras (4) , Dany Anglicheau (5) , Valerie Galantine (6) , Arwa Jalal Eddine (7) , Clément Gosset (8) , Franck Pourcine (9) , Mohammed Zarhrate (10) , Jean-Baptiste Gibier (11) , Elena Rensen (12) , Stefano Pietropaoli (13) , Giovanna Barba-Spaeth (13) , Jean-Paul Duong-Van-Huyen (5) , Thierry Molina (5) , Florian Mueller (12) , Christophe Zimmer (12) , Marco Pontoglio (1) , Fabiola Terzi (1) , Marion Rabant (1, 5)

1 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
2 Département de Pathologie [CHU Necker]
3 CHI Poissy-Saint-Germain
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 Hôpital Necker - Enfants Malades [AP-HP]
6 CHU Pointe-à-Pitre/Abymes [Guadeloupe]
7 Hôpital Foch [Suresnes]
8 CHU La Réunion - Centre Hospitalier Universitaire de La Réunion
9 CHM - Centre Hospitalier de Melun
10 UAR 3633 / US24 - Structure Fédérative de Recherche Necker
11 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
12 Imagerie et Modélisation - Imaging and Modeling
13 Virologie Structurale - Structural Virology

Acute kidney injury (AKI) is one of the most important complications in COVID-19 patients and is considered a negative prognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and its contribution 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, we showed that the SARS-CoV-2 infects living renal cells and that infection, which parallels renal ACE2 expression levels, is associated to increase death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures in SARS-CoV-2 infected kidneys as compared to healthy kidneys and non-COVID-19 ATI kidneys. On the other hand, we demonstrated that SARS-CoV-2 and Hantavirus, two RNA viruses, activated different genetic networks despite they triggered the same pathological lesions. Finally, we identified XAF1 as a critical target of SARS-CoV-2 infection. In conclusion, this study demonstrates that SARS-CoV2 can directly infect living renal cells and identified specific druggable molecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function in severely affected COVID-19 patients.

Domaines: Sciences du Vivant [q-bio]

Pierre Isnard, Paul Vergnaud, Serge Garbay, Matthieu Jamme, Maeva Eloudzeri, et al.. A specific molecular signature in SARS-CoV-2 infected kidney biopsies. JCI Insight, In press, pp.e165192. ⟨10.1172/jci.insight.165192⟩. ⟨pasteur-04004769⟩