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

Abstract

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.

Potential Alternative Receptors for SARS-CoV-2-Induced Kidney Damage: TLR-4, KIM-1/TIM-1, and CD147

“…Transcriptome analysis has identified common pathways and molecular biomarkers for COVID-19, AKI, and CKD [ 125 ]. These findings were echoed in a larger study on renal biopsies from patients with COVID-19, which showed that a major pathological renal feature from COVID-19 resonated as an acute tubular injury [ 126 ]. However, whether the SARS-CoV-2 virus does in fact infect kidney cells in order to replicate remains controversial.…”

Disfunções Orgânicas pela Covid-19

“…Outras condições pró-trombóticas hereditárias ou adquiridas, como púrpura trombocitopênica trombótica e síndrome hemolítico-urêmica atípica, também podem contribuir para a disfunção endotelial e coagulopatia em pacientes com Covid-19, assim como a ativação viral direta do sistema complemento. Estudos apontam para a importância do controle da ativação do complemento e da microangiopatia trombótica, que são mecanismos evidentes da lesão renal (Isnard, et al, 2023).…”

“…Afetou a população mundial com mais de 760 milhões de casos confirmados. Desde então, a Covid-19 se alastrou rapidamente pelo mundo, se tornou uma pandemia global afetando mais de 200 países, com um efeito sem precedentes não apenas na saúde pública, mas também nas atividades sociais e econômicas (Isnard, et al, 2023).…”