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      Single‐cell RNA sequencing analysis of human kidney reveals the presence of ACE2 receptor: A potential pathway of COVID‐19 infection

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          Abstract

          Background

          A novel coronavirus called SARS‐Cov‐2, which shared 82% similarity of genome sequence with SARS‐CoV, was found in Wuhan in late December of 2019, causing an epidemic outbreak of novel coronavirus‐induced pneumonia with dramatically increasing number of cases. Several organs are vulnerable to COVID‐19 infection. Acute kidney injury (AKI) was reported in parts of case‐studies reporting characteristics of COVID‐19 patients. This study aimed at analyzing the potential route of SARS‐Cov‐2 entry and mechanism at cellular level.

          Method

          Single‐cell RNA sequencing (scRNA‐seq) technology was used to obtain evidence of potential route and ACE2 expressing cell in renal system for underlying pathogenesis of kidney injury caused by COVID‐19. The whole process was performed under R with Seurat packages. Canonical marker genes were used to annotate different types of cells.

          Results

          Ten different clusters were identified and ACE2 was mainly expressed in proximal tubule and glomerular parietal epithelial cells. From Gene Ontology (GO) & KEGG enrichment analysis, imbalance of ACE2 expression, renin‐angiotensin system (RAS) activation, and neutrophil‐related processes were the main issue of COVID‐19 leading kidney injury.

          Conclusion

          Our study provided the cellular evidence that SARS‐Cov‐2 invaded human kidney tissue via proximal convoluted tubule, proximal tubule, proximal straight tubule cells, and glomerular parietal cells by means of ACE2‐related pathway and used their cellular protease TMPRSS2 for priming.

          Abstract

          Several organs are vulnerable to potential infection of COVID‐19 except lung, such as liver, digestive system, reproductive system and urinary system, and SARS‐CoV‐2 was separated from patients’ urine. Consequently, we hypothesized that COVID‐19 might invade human kidney causing renal injury, and this is the first study investigating the potential route of COVID‐19 leading kidney injury.

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          Most cited references34

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

            Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
            In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Nanshan Chen, Min Zhou, Xuan Dong … (2022)
              Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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                Author and article information

                Contributors
                Jieruo Li: ilorugaie@163.com
                Jinghua Pan:
                ORCID: https://orcid.org/0000-0003-3741-3397
                huajanve@foxmail.com
                Journal
                Journal ID (nlm-ta): Mol Genet Genomic Med
                Journal ID (iso-abbrev): Mol Genet Genomic Med
                Journal ID (doi): 10.1002/(ISSN)2324-9269
                Journal ID (publisher-id): MGG3
                Title: Molecular Genetics & Genomic Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2324-9269
                Publication date (Electronic): 03 August 2020
                Electronic Location Identifier: e1442
                Affiliations
                [ 1 ] First Affiliated Hospital of Jinan University Guangzhou Guangdong China
                [ 2 ] Pediatric Cardiac Surgery Center National Center for Cardiovascular Disease and Fuwai Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China
                [ 3 ] First Medical College of Southern Medical University Guangzhou Guangdong China
                [ 4 ] Heyu Health Technology Co Ltd. Guangzhou Guangdong China
                Author notes
                [*] [* ] Correspondence

                Jieruo Li, Department of Joint and Sport Medicine, First Affiliated Hospital of Jinan University, 613 Huangpu West Avenue, Guangzhou, Guangdong, China.

                Email: ilorugaie@ 123456163.com

                Jinghua Pan, Department of General Surgery, First Affiliated Hospital of Jinan University, 613 Huangpu West Avenue, Guangzhou, Guangdong, China.

                Email: huajanve@ 123456foxmail.com

                Author information
                https://orcid.org/0000-0003-3741-3397
                Article
                Publisher ID: MGG31442
                DOI: 10.1002/mgg3.1442
                PMC ID: 7435545
                PubMed ID: 32744436
                SO-VID: 73ea99f9-692f-49f3-bf4d-53ec928842c5
                Copyright © © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 June 2020
                Date revision received : 28 June 2020
                Date accepted : 14 July 2020
                Page count
                Figures: 6, Tables: 1, Pages: 11, Words: 12617
                Funding
                Funded by: Chair Professor Foundation of the First Affiliated Hospital of JinanUniversity
                Award ID: 702023
                Funded by: Guangdong Basic and Applied Basic Research Fund Project
                Award ID: 2019A1515110543
                Funded by: Fundamental Research Business Expenses of Central Universities
                Award ID: 11620306
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                edited-state corrected-proof
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.7 mode:remove_FC converted:19.08.2020

                Keywords: ace2,covid‐19,kidney,sars‐cov‐2,scrna‐seq
                Data availability:
                Keywords: ace2, covid‐19, kidney, sars‐cov‐2, scrna‐seq

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