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      Genetic susceptibility of COVID-19: a systematic review of current evidence

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          Abstract

          Introduction

          While COVID-19 pandemic continues to spread worldwide, researchers have linked patterns of traits to poor disease outcomes. Risk factors for COVID-19 include asthma, elderly age, being pregnant, having any underlying diseases such as cardiovascular disease, diabetes, obesity, and experiencing lifelong systemic racism. Recently, connections to certain genes have also been found, although the susceptibility has not yet been established. We aimed to investigate the available evidence for the genetic susceptibility to COVID-19.

          Methods

          This study was a systematic review of current evidence to investigate the genetic susceptibility of COVID-19. By systematic search and utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct, we retrieved all the related papers and reports published in English from December 2019 to September 2020.

          Results

          According to the findings, COVID-19 uses the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. Previous studies have shown that people with ACE2 polymorphism who have type 2 transmembrane serine proteases (TMPRSS2) are at high risk of SARS-CoV-2 infection. Also, two studies have shown that males are more likely to become infected with SARS-CoV-2 than females. Besides, research has also shown that patients possessing HLA-B*15:03 genotype may become immune to the infection.

          Conclusion

          Combing through the genome, several genes related to immune system’s response were related to the severity and susceptibility to the COVID-19. In conclusion, a correlation was found between the ACE2 levels and the susceptibility to SARS-CoV-2 infection.

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          Most cited references59

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

          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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            Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

            Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells 1,2 . Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2) 3,4 , isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. Supplementary information The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.
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              Cell entry mechanisms of SARS-CoV-2

              Significance A key to curbing SARS-CoV-2 is to understand how it enters cells. SARS-CoV-2 and SARS-CoV both use human ACE2 as entry receptor and human proteases as entry activators. Using biochemical and pseudovirus entry assays and SARS-CoV as a comparison, we have identified key cell entry mechanisms of SARS-CoV-2 that potentially contribute to the immune evasion, cell infectivity, and wide spread of the virus. This study also clarifies conflicting reports from recent studies on cell entry of SARS-CoV-2. Finally, by highlighting the potency and the evasiveness of SARS-CoV-2, the study provides insight into intervention strategies that target its cell entry mechanisms.
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                Author and article information

                Contributors
                s_a_alinaghi@yahoo.com
                m.mehrtak@arums.ac.ir
                mohsenipour_mehrzad@yahoo.com
                pegah.mirzapour@yahoo.com
                barzegaryalireza@gmail.com
                pedramhabibi98@gmail.com
                b.moradmand_badie@blackdog.org.au
                amir.masoud.afsahi@gmail.com
                aa-karimi@student.tums.ac.ir
                heydari.mohammad12@yahoo.com
                es.mehraeen@gmail.com
                omiddadras@yahoo.com
                sabatier.jm1@gmail.com
                voltarellifa@gmail.com
                Journal
                Eur J Med Res
                Eur J Med Res
                European Journal of Medical Research
                BioMed Central (London )
                0949-2321
                2047-783X
                20 May 2021
                20 May 2021
                2021
                : 26
                : 46
                Affiliations
                [1 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Iranian Research Center for HIV/AIDS, , Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, ; Tehran, Iran
                [2 ]GRID grid.411426.4, ISNI 0000 0004 0611 7226, Healthcare Services Management, School of Medicine and Allied Medical Sciences, , Ardabil University of Medical Sciences, ; Ardabil, Iran
                [3 ]GRID grid.411463.5, ISNI 0000 0001 0706 2472, School of Medicine, , Islamic Azad University, ; Tehran, Iran
                [4 ]GRID grid.1005.4, ISNI 0000 0004 4902 0432, Black Dog Institute, University of New South Wales, ; Sydney, Australia
                [5 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Radiology, School of Medicine, , University of California, San Diego (UCSD), ; San Diego, CA USA
                [6 ]GRID grid.411705.6, ISNI 0000 0001 0166 0922, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
                [7 ]Department of Health Information Technology, Khalkhal University of Medical Sciences, 1419733141 Khalkhal, Iran
                [8 ]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Department of Global Health and Socioepidemiology, Graduate School of Medicine, , Kyoto University, ; Kyoto, Japan
                [9 ]GRID grid.5399.6, ISNI 0000 0001 2176 4817, Institut deNeuro-Physiopathologie (INP), UMR 7051, Faculté de Pharmacie, , Université Aix-Marseille, ; 27 Bd Jean Moulin, 13385 Marseille Cedex, France
                [10 ]GRID grid.411206.0, ISNI 0000 0001 2322 4953, Graduation Program of Health Sciences, Faculty of Medicine, , Federal University of Mato Grosso, ; Cuiabá, Brazil
                Author information
                http://orcid.org/0000-0003-4108-2973
                Article
                516
                10.1186/s40001-021-00516-8
                8135169
                34016183
                ee14fc5b-ddfa-4070-83a0-b744ea10568a
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 22 February 2021
                : 6 May 2021
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Medicine
                genetic susceptibility,genetic vulnerability,genetic probability,covid-19,sars-cov-2
                Medicine
                genetic susceptibility, genetic vulnerability, genetic probability, covid-19, sars-cov-2

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