Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

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Abstract

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.

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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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A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Contributors

Ezequiel Álvarez: Role: Academic Editor

Alexander E. Kalyuzhny: Role: Academic Editor

Journal

Journal ID (nlm-ta): Cells

Journal ID (iso-abbrev): Cells

Journal ID (publisher-id): cells

Title: Cells

Publisher: MDPI

ISSN (Electronic): 2073-4409

Publication date (Electronic): 11 July 2021

Publication date Collection: July 2021

Volume: 10

Issue: 7

Electronic Location Identifier: 1752

Affiliations

[1 ]Department of Emergency Medicine, Foundation of Policlinico Agostino Gemelli-IRCCS, Catholic University of Sacred Heart, 00168 Rome, Italy; francesco.franceschi@ 123456unicatt.it (F.F.); andrea.piccioni@ 123456policlinicogemelli.it (A.P.); veronica.ojetti@ 123456unicatt.it (V.O.); saviange@ 123456libero.it (A.S.)

[2 ]Department of Anesthesia and Critical Care, AON SS Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; tatsiana_romenskaya@ 123456yahoo.it (T.R.); fpiccolella@ 123456ospedale.al.it (F.P.); fracca@ 123456ospedale.al.it (F.R.); lon.yaro@ 123456gmail.com (Y.L.)

[3 ]Foundation Ospedale Alba-Bra and Department of Anesthesia, Critical Care and Emergency Medicine, Pietro and Michele Ferrero Hospital, 12051 Verduno, Italy

[4 ]Department of Emergency Medicine, AON SS Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; michelefidel.tassi@ 123456gmail.com

[5 ]Department of Health Sciences, University Magna Graecia, 88100 Catanzaro, Italy; l.abenavoli@ 123456unicz.it

[6 ]Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy; barbara.canonico@ 123456uniurb.it (B.C.); mariele.montanari@ 123456uniurb.it (M.M.); loris.zamai@ 123456uniurb.it (L.Z.)

[7 ]National Institute for Nuclear Physics (INFN)-Gran Sasso National Laboratory (LNGS), 67100 Assergi L’Aquila, Italy

[8 ]Department of Sensory Organs, Sapienza University of Rome, 00185 Rome, Italy; marco.artico@ 123456uniroma1.it

[9 ]Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy; kiarobba@ 123456gmail.com

Author notes

[* ]Correspondence: christian.zanza@ 123456live.it

Author information

Ludovico Abenavoli https://orcid.org/0000-0002-5922-1524

Andrea Piccioni https://orcid.org/0000-0001-5703-8737

Angela Saviano https://orcid.org/0000-0002-2820-7180

Barbara Canonico https://orcid.org/0000-0003-3383-715X

Mariele Montanari https://orcid.org/0000-0003-4848-3390

Loris Zamai https://orcid.org/0000-0002-4361-1026

Marco Artico https://orcid.org/0000-0002-8786-7007

Yaroslava Longhitano https://orcid.org/0000-0001-8831-1361

Article

Publisher ID: cells-10-01752

DOI: 10.3390/cells10071752

PMC ID: 8306543

SO-VID: 417ba792-25c9-4e46-b2a2-a9b840db82f9

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

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Novel Coronavirus Disease COVID-19

Most cited references 156

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

A pneumonia outbreak associated with a new coronavirus of probable bat origin

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

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