Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Bo Diao; Chenhui Wang; Rongshuai Wang; Zeqing Feng; Yingjun Tan; Huiming Wang; Changsong Wang; Liang Liu; Ying Liu; Yueping Liu; Gang Wang; Zilin Yuan; Liang Ren; Yuzhang Wu; Yongwen Chen

While SARS-CoV-2 is a cytopathic virus which can also directly induce renal tubular injury during infection and replication, the occurrence of such injury may also initiate complex immune responses. After all, although host immune cells can infiltrate into infected tissue to counteract viral replication, hyperactivation of immune cells may instead promote fibrosis, induce epithelial cell apoptosis, and cause microvasculature changes. [19] [20] [21] We report here that SARS-CoV-2 virus recruits high levels of CD68 + macrophages to infiltrate into the tubulointerstitium (Figure 4A) , suggesting that proinflammatory cytokines derived from macrophages would induce tubular damage. Both clinical and experimental models suggest that the abnormal presence of serum-derived complement components in the tubular lumen leads to the assembly of the complement C5b-9 (via the alternative pathway) on the apical brush border of tubular epithelial cells (TECs), and that this is an important factor in the pathogenesis of tubulointerstitial damage. [22] [23] [24] We here observed that SARS-CoV-2 initiates complement C5b-9 assembly and deposition on tubules ( Figure 4B) . We therefore demonstrate that SARS-CoV-2 causes tubular damage through direct cytotoxicity, but also initiates immune-mediates tubule pathogenesis.