Identification of common molecular signatures of SARS-CoV-2 infection and its influence on acute kidney injury and chronic kidney disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the main cause of COVID-19, causing hundreds of millions of confirmed cases and more than 18.2 million deaths worldwide. Acute kidney injury (AKI) is a common complication of COVID-19 that leads to an increase in mortality, especially in intensive care unit (ICU) settings, and chronic kidney disease (CKD) is a high risk factor for COVID-19 and its related mortality. However, the underlying molecular mechanisms among AKI, CKD, and COVID-19 are unclear. Therefore, transcriptome analysis was performed to examine common pathways and molecular biomarkers for AKI, CKD, and COVID-19 in an attempt to understand the association of SARS-CoV-2 infection with AKI and CKD. Three RNA-seq datasets (GSE147507, GSE1563, and GSE66494) from the GEO database were used to detect differentially expressed genes (DEGs) for COVID-19 with AKI and CKD to search for shared pathways and candidate targets. A total of 17 common DEGs were confirmed, and their biological functions and signaling pathways were characterized by enrichment analysis. MAPK signaling, the structural pathway of interleukin 1 (IL-1), and the Toll-like receptor pathway appear to be involved in the occurrence of these diseases. Hub genes identified from the protein-protein interaction (PPI) network, including DUSP6, BHLHE40, RASGRP1, and TAB2, are potential therapeutic targets in COVID-19 with AKI and CKD. Common genes and pathways may play pathogenic roles in these three diseases mainly through the activation of immune inflammation. Networks of transcription factor (TF)-gene, miRNA-gene, and gene-disease interactions from the datasets were also constructed, and key gene regulators influencing the progression of these three diseases were further identified among the DEGs. Moreover, new drug targets were predicted based on these common DEGs, and molecular docking and molecular dynamics (MD) simulations were performed. Finally, a diagnostic model of COVID-19 was established based on these common DEGs. Taken together, the molecular and signaling pathways identified in this study may be related to the mechanisms by which SARS-CoV-2 infection affects renal function. These findings are significant for the effective treatment of COVID-19 in patients with kidney diseases.

A survey on acute kidney injury in severely and critically ill COVID-19 patients without chronic kidney disease.

BACKGROUND: Research has shown that acute kidney injury (AKI) has a noticeable incidence in critically ill patients with coronavirus disease 2019 (COVID-19). Patients with prior renal insufficiency are particularly susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), due to their immune dysfunction. However, most patients with COVID-19 do not have a history of kidney dysfunction, and few studies have focused on the incidence of AKI among COVID-19 patients without chronic kidney disease (CKD). In this study, we aimed to investigate the occurrence of AKI in severely and critically ill COVID-19 patients, with a particular focus on those without a CKD history. METHODS: A single-center retrospective study of 96 patients with COVID-19 in China between February 7 and March 3, 2020 was conducted. All patients were diagnosed by nucleic acid test (NAT) for SARS-CoV-2. Enrolled patients were divided into the severely or critically ill group according to the defined criteria. Patients' epidemiological, clinical, and laboratory characteristics, along with their treatment information, were collected from the medical history system. The occurrence of AKI was compared between the severe and critical patients, and between patients with or without a history of CKD. The diagnostic criteria for AKI included an increase in the serum creatinine level to ≥1.5-fold the level at baseline within 7 days according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Renal outcomes were defined as AKI or non-AKI. RESULTS: Four patients (4.2%) developed AKI, all of whom were in the critically ill group, and 3 (75%) of whom died. Out of the 90 severely and critically ill COVID-19 patients without CKD, 3 (3.3%) patients developed AKI; out of the 6 patients with CKD, 1 (16.7%) patient developed AKI. Age, disease severity, procalcitonin, C-reactive protein, and interleukin-6 were correlated with AKI onset in severely and critically ill COVID-19 patients, while lymphocyte count and estimated glomerular filtration rate at admission were inversely related to the development of AKI. CONCLUSIONS: Only 3.3% of severely and critically ill COVID-19 patients without CKD in our research cohort developed AKI. Critically ill patients may be more susceptible to AKI than severely ill patients.

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.

BACKGROUND: Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system. METHODS: We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2. RESULTS: Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression. CONCLUSION: This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

The epidemiology and clinical information about COVID-19.

In December 2019, pneumonia of unknown cause occurred in Wuhan, Hubei Province, China. On 7 January 2020, a novel coronavirus, named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was identified in the throat swab sample of one patient. The World Health Organization (WHO) announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). Currently, COVID-19 has spread widely around the world, affecting more than seventy countries. China, with a huge burden of this disease, has taken strong measures to control the spread and improve the curative rate of COVID-19. In this review, we summarized the epidemiological characteristics, clinical features, diagnosis, treatment, and prognosis of COVID-19. A comprehensive understanding will help to control the disease.