Abstract
Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient’s condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.
Highlights
The outbreak of coronavirus disease 2019 (COVID-19) has evolved into a global pandemic
In order to investigate the localization of both the ACE2 and transmembrane protease serine 2 (TMPRSS2) in the human kidney, we firstly performed bioinformatic analysis on public single-cell RNA sequencing datasets based on two different platforms (10X Genomics and Microwell-seq)
Intense signals were observed mainly in the distal tubular cells and seldom in the proximal tubular cells of COVID-19 patient’s kidney tissues (Figure 1D). These results indicated that the renal distal tubule is a direct target for SARS-CoV-2 infection; SARS-CoV-2 may enter the distal tubular cells in an ACE2-independent manner, and which protein served as the receptor for SARS-CoV-2 on TMPRSS2+ cells is unknown
Summary
The outbreak of coronavirus disease 2019 (COVID-19) has evolved into a global pandemic. Until October 10, 2020, there were over 36 million confirmed cases, and 1,056,186 deaths have been reported (WHO, 2019). Among COVID-19 patients, acute kidney injury (AKI) is one of the most prevalent complications (36.6%) and is associated with a poor prognosis (Cheng et al, 2020b; Hirsch et al, 2020). It is still not clear that AKI caused by COVID-19 was either directly a damage of infection or a manifestation of systemic inflammatory response. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the pathogen of the COVID-19 pandemic. Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Previous studies (Hoffmann et al, 2020; Zheng et al, 2020)
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