COVID-19infection:ACE2,pregnancyand preeclampsia
RecentstudiessuggestthatCOVID-19infectionhasamild to moderatecourseinpregnantwomen[1,2].Thiscouldberelatedto theiryoungerage.DatafromtheItalianSurveillanceSystemshow thatinwomenofreproductiveage(20–39years)thelethalityrate islow (median 0.1 %;range 0.05–0.16) and lowerthan in men (median0.4%;range0.30 0.47).Afterwarditincreasessteadily from0.5%at40–49yearstoover20%at80–89years,butthe imbalancebetweenwomenandmenremains[2].
Pre-clinical models suggest that angiotensin-converting en-zyme2(ACE2)upregulationconfersprotectiveeffectsinacutelung injury. ACE2,overexpressed in women, is the enzyme through which coronaviruses bind to their target cells. In women of reproductiveageoestrogenscouldbeprotectivebyincreasingthe expressionof ACE2. The overexpression of ACE2 could alsobe explainedbytheobservationthatintheinactivatedXchromosome therearesomeactiveregionsencodingforACE2thusprotecting alsopostmenopausalwomen.COVID-19enterstargetcellsbyACE2 mediation: virus-ACE2 complex formation could lead to ACE2 inactivation.Extra copiesofACE2in womenwould continue to carryonprotection[2].Couldtherebeotherreasonsbesideage andbeingwomentoexplainthemildtomoderatecourseofthe diseaseinpregnancy?Animalstudieshavedemonstratedthatin normalpregnancythereisanoverproductionofACE2,beingthe placentaandtheuterusimportantsourcesoftheenzyme.ACE2 exhibitshighcatalyticefficiencytogenerateAngiotensin1–7 (Ang-1–7)thathasavasodilatoryactionandatthesametimeinactivates the vasoconstrictor Angiotensin II. Ang-1–7 plasma levels are significantly increased in third trimester pregnant women compared to non pregnant [3]. This would contribute to the systemicvasodilationanddecreaseinbloodpressureandtoother physiologicaladaptationsthatoccurinnormalpregnancy.
Interestingly,Ang-1–7plasmalevelsarelowerinpregnancies complicatedbypre-eclampsiathaninphysiologicalpregnancies [4].Pre-eclampsiaisapregnancyrelatedsyndromecharacterized bytheappearanceofhypertensionandproteinuriaafter20weeks ofgestationalage.Itsaetiologyisnotcompletelyunderstood,but there is agreement as far as its pathogenesis is concerned: an exaggeratedinflammatoryresponseleadingtoendothelialdamage
[5].AlsothemostsevereformsofCOVID-19areexplainedbyan excessiveinflammatoryresponse,withhighlevelsofproin flam-matorycytokines(IL-6, TNF-alfa,IFN-gamma, etc)that are also overexpressed in mesenchymal stromal cells of pre-eclamptic placentas [6,7]. Investigation in this direction could help to developnewstrategiesforthepreventionandtreatmentofboth pre-eclampsiaandCOVID-19.
DeclarationofCompetingInterest
Theauthorsreportednodeclarationsofinterest.
References
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TulliaTodros UniversityofTurin,Italy BiancaMasturzo*
CittàdellaSaluteedellaScienza,Turin,Italy SilviaDeFrancia UniversityofTurin,Italy
* Correspondingauthor. E-mailaddress:[email protected](B.Masturzo).
Received1June2020
https://doi.org/10.1016/j.ejogrb.2020.08.007
0301-2115/©2020ElsevierB.V.Allrightsreserved.
EuropeanJournalofObstetrics&GynecologyandReproductiveBiology253(2020)330
ContentslistsavailableatScienceDirect
