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

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

BACKGROUND The outbreak of a novel coronavirus (SARS-CoV-2, previously provisionally named 2019 novel coronavirus or 2019-nCoV) since December 2019 in Wuhan, China, has become an emergency of major international concern. Apart from the respiratory system, it is unclear whether SARS-CoV-2 can also directly infect other tissues such as the kidney or induce acute renal failure. METHODS We conducted a retrospective analysis of estimated glomerular filtration rate (eGFR) along with other clinical parameters from 85 patients with laboratory-confirmed COVID-19 admitted to a hospital in Wuhan from January 17, 2020 to March 3, 2020. Kidney tissues from six patients with postmortem examinations were analyzed by Hematoxylin and Eosin (H&E) and in situ expression of viral nucleocaspid protein (NP) antigen, immune cell markers (CD8, CD68 and CD56) and the complement C5b-9 was detected by immunohistochemistry. Moreover, the viral particles in kidneys were also investigated by transmission electronic microscope (EM). RESULTS 27.06% (23/85) patients exhibited acute renal failure (ARF). The eldery patients and cases with comorbidities such as hypertension and heart failure more easily developed ARF (65.22% vs 24.19%, p< 0.001; 69.57% vs 11.29%, p< 0.001, respectively). H&E staining demonstrated kidney tissues from postmortems have severe acute tubular necrosis and lymphocyte infiltration. Immunohistochemistry showed that SARS-CoV-2 NP antigen was accumulated in kidney tubules. EM observation also demonstrated that viruses- like particles are visible in the kidneys. Viral infection not only induces CD68+ macrophages infiltrated into tubulointerstitium, but also enhances complement C5b-9 deposition on tubules. CONCLUSIONS SARS-CoV-2 induces ARF in COVID-19 patients. Viruses directly infect human kidney tubules to induce acute tubular damage. The viruses not only have direct cytotoxicity, but also initiate CD68+ macrophage together with complement C5b-9 deposition to mediate tubular pathogenesis.