Expression profiles revealed potential kidney injury caused by SARS-CoV-2: a systematic analysis of ACE2 and clinical lessons learned from this discovery.

ABSTRACT

BACKGROUND: Novel Coronavirus disease 2019 (COVID-19) was first detected in pneumonia patients in Wuhan, China in December 2019. Based on the current understanding, COVID-19 has become a global issue. Presumably, numerous studies have found that SARS-CoV-2 also transpires in kidney tissue with permanent viral loads. However, it is elusive as to whether SARS-CoV-2 can directly damage the kidney or induce acute renal failure. Hence, to comprehensively understand the impact of COVID-19 on kidney damage, we conducted a retrospective series of case studies to assess kidney functions. Additionally, ACE2 distribution in kidney tissue was analyzed through RNAseq data in open-access databases. RESULTS: According to the findings from transcriptome analysis, we revealed higher ACE2 expression levels in females than males. Similar results were more noticeable in the elderly than in young adults. Furthermore, single-cell RNA sequencing data analysis showed high ACE2 expression in kidney tubule and collecting duct principal cells as well as glomerular parietal epithelial cells. On their admission, the patient's serum creatinine and blood urea nitrogen (BUN) were elevated to between 36.13% and 16.80%, respectively. The estimated glomerular filtration rate (EGFR) of < 60 ml/min per 1.73 m2 was reported in 10.92 % of the patients. Notably, at admission, increased BUN time varied linearly following the generalized additive mixed model. Thus, the hourly-increase of BUN in patients was 0.495 (95%CI 0.263, 0.726). CONCLUSION: Based on clinical findings, it was ascertained that COVID-19 can damage renal function, but it seldom causes acute renal failure. Coronavirus may directly bind to ACE2-positive cells and damage kidney tissue in the analysis of scRNA-seq data in kidney tissue. Therefore, this evidence suggests that kidney tissue act as the SARS-CoV-2 infection site and the findings could provide insight into the pathophysiology of kidney damage. METHODS: We systematically analyzed ACE2 expression profiles in organs based on open-access datasets for healthy individuals. Meanwhile, single-cell sequencing data for kidney samples were collected and analyzed. Assessments on kidney functions were conducted on 119 selected COVID-19 positive patients admitted from 10th February - 18th March 2020, in hospital in Wuhan City, Hubei Province. Consequently, their clinical records and laboratory findings, such as the estimated glomerular filtration rate (eGFR), Blood Urea Nitrogen (BUN), Creatinine, and Comorbidities, were collected.