Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection

TLDR

It remains unclear whether SARS‑CoV‑2 can directly infect human kidney and cause acute kidney injury. The study retrospectively analyzed clinical data from 85 COVID‑19 patients and performed kidney histopathology on six post‑mortem cases. Twenty‑seven percent of patients developed AKI, with older age and comorbidities increasing risk; autopsy kidneys showed moderate‑to‑severe tubular damage, viral RNA and spike/nucleocapsid proteins localized to ACE2‑positive tubules, upregulation of hypoxia‑related molecules, macrophage infiltration, and complement deposition, indicating direct viral infection drives tubular injury and AKI.

Abstract

Abstract It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.