ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman's and Bartter's Syndromes.
Identifieur interne : 000000 ( Main/Corpus ); suivant : 000001ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman's and Bartter's Syndromes.
Auteurs : Lorenzo A. Cal ; Matteo Rigato ; Luca Sgarabotto ; Lisa Gianesello ; Giovanni Bertoldi ; Verdiana Ravarotto ; Paul A. DavisSource :
- Frontiers in medicine [ 2296-858X ] ; 2021.
Abstract
COVID-19 is spreading globally with the angiotensin converting enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This raised concerns how ACE2 and the Renin-Angiotensin (Ang)-System (RAS) are to be dealt with given their roles in hypertension and their involvement in COVID-19's morbidity and mortality. Specifically, increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by increasing SARS-CoV-2 binding sites. However, ACE2 is part of the protective counter-regulatory ACE2-Ang1-7-MasR axis, which opposes the classical ACE-AngII-AT1R regulatory axis. We used Gitelman's and Bartter's syndromes (GS/BS) patients, rare genetic tubulopathies that have endogenously increased levels of ACE2, to explore these issues. Specifically, 128 genetically confirmed GS/BS patients, living in Lombardia, Emilia Romagna and Veneto, the Northern Italy hot spots for COVID-19, were surveyed via telephone survey regarding COVID-19. The survey found no COVID-19 infection and absence of COVID-19 symptoms in any patient. Comparison analysis with the prevalence of COVID-19 in those regions showed statistical significance (p < 0.01). The results of the study strongly suggest that increased ACE2 does not increase risk of COVID-19 and that ACEi and ARBs by blocking excessive AT1R-mediated Ang II activation might favor the increase of ACE2-derived Ang 1-7. GS/BS patients' increased ACE2 and Ang 1-7 levels and their characteristic chronic metabolic alkalosis suggest a mechanism similar to that of chloroquine/hydroxychloroquine effect on ACE2 glycosylation alteration with resulting SARS-COV-2 binding inhibition and blockage/inhibition of viral entry. Studies from our laboratory are ongoing to explore GS/BS ACE2 glycosylation and other potential beneficial effects of BS/GS. Importantly, the absence of frank COVID-19 or of COVID-19 symptoms in the BS/GS patients cohort, given no direct ascertainment of COVID-19 status, suggest that elevated ACE2 levels as found in GS/BS patients at a minimum render COVID-19 infection asymptomatic and thus that COVID-19 symptoms are driven by ACE2 levels.
DOI: 10.3389/fmed.2021.647319
PubMed: 34017843
PubMed Central: PMC8129173
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman's and Bartter's Syndromes.</title><author><name sortKey="Cal, Lorenzo A" sort="Cal, Lorenzo A" uniqKey="Cal L" first="Lorenzo A" last="Cal">Lorenzo A. Cal</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Rigato, Matteo" sort="Rigato, Matteo" uniqKey="Rigato M" first="Matteo" last="Rigato">Matteo Rigato</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Sgarabotto, Luca" sort="Sgarabotto, Luca" uniqKey="Sgarabotto L" first="Luca" last="Sgarabotto">Luca Sgarabotto</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gianesello, Lisa" sort="Gianesello, Lisa" uniqKey="Gianesello L" first="Lisa" last="Gianesello">Lisa Gianesello</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Bertoldi, Giovanni" sort="Bertoldi, Giovanni" uniqKey="Bertoldi G" first="Giovanni" last="Bertoldi">Giovanni Bertoldi</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Ravarotto, Verdiana" sort="Ravarotto, Verdiana" uniqKey="Ravarotto V" first="Verdiana" last="Ravarotto">Verdiana Ravarotto</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Davis, Paul A" sort="Davis, Paul A" uniqKey="Davis P" first="Paul A" last="Davis">Paul A. Davis</name><affiliation><nlm:affiliation>Department of Nutrition, University of California, Davis, Davis, CA, United States.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:34017843</idno><idno type="pmid">34017843</idno><idno type="doi">10.3389/fmed.2021.647319</idno><idno type="pmc">PMC8129173</idno><idno type="wicri:Area/Main/Corpus">000000</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000000</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman's and Bartter's Syndromes.</title><author><name sortKey="Cal, Lorenzo A" sort="Cal, Lorenzo A" uniqKey="Cal L" first="Lorenzo A" last="Cal">Lorenzo A. Cal</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Rigato, Matteo" sort="Rigato, Matteo" uniqKey="Rigato M" first="Matteo" last="Rigato">Matteo Rigato</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Sgarabotto, Luca" sort="Sgarabotto, Luca" uniqKey="Sgarabotto L" first="Luca" last="Sgarabotto">Luca Sgarabotto</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gianesello, Lisa" sort="Gianesello, Lisa" uniqKey="Gianesello L" first="Lisa" last="Gianesello">Lisa Gianesello</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Bertoldi, Giovanni" sort="Bertoldi, Giovanni" uniqKey="Bertoldi G" first="Giovanni" last="Bertoldi">Giovanni Bertoldi</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Ravarotto, Verdiana" sort="Ravarotto, Verdiana" uniqKey="Ravarotto V" first="Verdiana" last="Ravarotto">Verdiana Ravarotto</name><affiliation><nlm:affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Davis, Paul A" sort="Davis, Paul A" uniqKey="Davis P" first="Paul A" last="Davis">Paul A. Davis</name><affiliation><nlm:affiliation>Department of Nutrition, University of California, Davis, Davis, CA, United States.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Frontiers in medicine</title><idno type="ISSN">2296-858X</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">COVID-19 is spreading globally with the angiotensin converting enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This raised concerns how ACE2 and the Renin-Angiotensin (Ang)-System (RAS) are to be dealt with given their roles in hypertension and their involvement in COVID-19's morbidity and mortality. Specifically, increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by increasing SARS-CoV-2 binding sites. However, ACE2 is part of the protective counter-regulatory ACE2-Ang1-7-MasR axis, which opposes the classical ACE-AngII-AT1R regulatory axis. We used Gitelman's and Bartter's syndromes (GS/BS) patients, rare genetic tubulopathies that have endogenously increased levels of ACE2, to explore these issues. Specifically, 128 genetically confirmed GS/BS patients, living in Lombardia, Emilia Romagna and Veneto, the Northern Italy hot spots for COVID-19, were surveyed <i>via</i> telephone survey regarding COVID-19. The survey found no COVID-19 infection and absence of COVID-19 symptoms in any patient. Comparison analysis with the prevalence of COVID-19 in those regions showed statistical significance (<i>p</i> < 0.01). The results of the study strongly suggest that increased ACE2 does not increase risk of COVID-19 and that ACEi and ARBs by blocking excessive AT1R-mediated Ang II activation might favor the increase of ACE2-derived Ang 1-7. GS/BS patients' increased ACE2 and Ang 1-7 levels and their characteristic chronic metabolic alkalosis suggest a mechanism similar to that of chloroquine/hydroxychloroquine effect on ACE2 glycosylation alteration with resulting SARS-COV-2 binding inhibition and blockage/inhibition of viral entry. Studies from our laboratory are ongoing to explore GS/BS ACE2 glycosylation and other potential beneficial effects of BS/GS. Importantly, the absence of frank COVID-19 or of COVID-19 symptoms in the BS/GS patients cohort, given no direct ascertainment of COVID-19 status, suggest that elevated ACE2 levels as found in GS/BS patients at a minimum render COVID-19 infection asymptomatic and thus that COVID-19 symptoms are driven by ACE2 levels.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">34017843</PMID><DateRevised><Year>2021</Year><Month>05</Month><Day>21</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2296-858X</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><PubDate><Year>2021</Year></PubDate></JournalIssue><Title>Frontiers in medicine</Title><ISOAbbreviation>Front Med (Lausanne)</ISOAbbreviation></Journal><ArticleTitle>ACE2 and SARS-CoV-2 Infection Risk: Insights From Patients With Two Rare Genetic Tubulopathies, Gitelman's and Bartter's Syndromes.</ArticleTitle><Pagination><MedlinePgn>647319</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fmed.2021.647319</ELocationID><Abstract><AbstractText>COVID-19 is spreading globally with the angiotensin converting enzyme (ACE)-2 serving as the entry point of SARS-CoV-2 virus. This raised concerns how ACE2 and the Renin-Angiotensin (Ang)-System (RAS) are to be dealt with given their roles in hypertension and their involvement in COVID-19's morbidity and mortality. Specifically, increased ACE2 expression in response to treatment with ACE inhibitors (ACEi) and Ang II receptor blockers (ARBs) might theoretically increase COVID-19 risk by increasing SARS-CoV-2 binding sites. However, ACE2 is part of the protective counter-regulatory ACE2-Ang1-7-MasR axis, which opposes the classical ACE-AngII-AT1R regulatory axis. We used Gitelman's and Bartter's syndromes (GS/BS) patients, rare genetic tubulopathies that have endogenously increased levels of ACE2, to explore these issues. Specifically, 128 genetically confirmed GS/BS patients, living in Lombardia, Emilia Romagna and Veneto, the Northern Italy hot spots for COVID-19, were surveyed <i>via</i> telephone survey regarding COVID-19. The survey found no COVID-19 infection and absence of COVID-19 symptoms in any patient. Comparison analysis with the prevalence of COVID-19 in those regions showed statistical significance (<i>p</i> < 0.01). The results of the study strongly suggest that increased ACE2 does not increase risk of COVID-19 and that ACEi and ARBs by blocking excessive AT1R-mediated Ang II activation might favor the increase of ACE2-derived Ang 1-7. GS/BS patients' increased ACE2 and Ang 1-7 levels and their characteristic chronic metabolic alkalosis suggest a mechanism similar to that of chloroquine/hydroxychloroquine effect on ACE2 glycosylation alteration with resulting SARS-COV-2 binding inhibition and blockage/inhibition of viral entry. Studies from our laboratory are ongoing to explore GS/BS ACE2 glycosylation and other potential beneficial effects of BS/GS. Importantly, the absence of frank COVID-19 or of COVID-19 symptoms in the BS/GS patients cohort, given no direct ascertainment of COVID-19 status, suggest that elevated ACE2 levels as found in GS/BS patients at a minimum render COVID-19 infection asymptomatic and thus that COVID-19 symptoms are driven by ACE2 levels.</AbstractText><CopyrightInformation>Copyright © 2021 Calò, Rigato, Sgarabotto, Gianesello, Bertoldi, Ravarotto and Davis.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Calò</LastName><ForeName>Lorenzo A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rigato</LastName><ForeName>Matteo</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sgarabotto</LastName><ForeName>Luca</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gianesello</LastName><ForeName>Lisa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bertoldi</LastName><ForeName>Giovanni</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ravarotto</LastName><ForeName>Verdiana</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Dialysis and Transplantation Unit, Department of Medicine, Nephrology, University of Padova, Padua, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davis</LastName><ForeName>Paul A</ForeName><Initials>PA</Initials><AffiliationInfo><Affiliation>Department of Nutrition, University of California, Davis, Davis, CA, United States.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>05</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Med (Lausanne)</MedlineTA><NlmUniqueID>101648047</NlmUniqueID><ISSNLinking>2296-858X</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ACE2</Keyword><Keyword MajorTopicYN="N">Bartter syndrome</Keyword><Keyword MajorTopicYN="N">Gitelman syndrome</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">angiotensin II receptor blockers</Keyword><Keyword MajorTopicYN="N">angiotensin conversing enzyme inhibitor</Keyword></KeywordList><CoiStatement>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>12</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>03</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>5</Month><Day>21</Day><Hour>6</Hour><Minute>34</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>5</Month><Day>22</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34017843</ArticleId><ArticleId IdType="doi">10.3389/fmed.2021.647319</ArticleId><ArticleId IdType="pmc">PMC8129173</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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