 real change? The more things change the more they stay the same! The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already surpassed the combined mortality inflicted by the severe acute respiratory syndrome (SARS) epidemic of 2002 and 2003 and the Middle East respiratory syndrome (MERS) epidemic of 2013. The pandemic is spreading at an exponential rate, with millions of people across the globe at risk of contracting SARS-CoV-2. Initial reports suggest that hypertension, diabetes, and cardiovascular diseases were the most frequent comorbidities in affected patients, and case fatality rates tended to be high in these individuals. In the largest Chinese study to date,1 which included 44 672 confirmed cases, preexisting comorbidities that had high mortality rates included cardiovascular disease (10.5%), diabetes (7.3%), and hypertension (6.0%). Patients with such comorbidities are commonly treated with renin angiotensin system blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). However, the use of ACEIs/ARBs in patients with COVID-19 or at risk of COVID-19 infection is currently a subject of intense debate. Below, we outline the mechanisms by which ACEIs/ARBs may be of benefit in those with COVID-19, what the current recommendations are for their use in infected patients, and suggested areas for further research.

SARS-CoV-2 uses the angiotensin-converting enzyme (ACE) 2 receptor for entry into target cells. ACE2 is predominantly expressed by epithelial cells of the lung, intestine, kidney, heart, and blood vessels. Both ACE and ACE2 belong to the ACE family of dipeptidyl carboxydipeptidases and exert distinct physiological functions. ACE cleaves angiotensin I to angiotensin II, which in turn binds and activates angiotensin II receptor type 1. This activation leads to vasoconstrictive, proinflammatory, and pro-oxidative effects. In contrast, ACE2 also degrades angiotensin II to angiotensin 1-7 and angiotensin I to angiotensin 1-9. When angiotensin 1-9 binds to the Mas receptor, it leads to anti-inflammatory, antioxidative, and vasodilatory effects. It is important to note that 2 forms of ACE2 exists: a structural transmembrane protein with extracellular domain that serves as a receptor for spike protein of SARS-CoV-2 and a soluble form that represents the circulating ACE2. Understanding the relationship between SARS-CoV-2 and
real change? The more things change the more they last out the like! The coronavirus disease 2019 (COVID-19) pandemic caused by severe acuate respiratory syndrome coronavirus 2 (SARS - CoV-2) has already surpassed the combine mortality inflict by the severe acute respiratory syndrome (SARS) epidemic of 2002 and 2003 and the Middle East respiratory syndrome (MERS) epidemic of 2013. The pandemic is spreading at an exponential pace, with million of people across the ball at risk of contracting SARS - CoV-2. Initial composition indicate that hypertension, diabetes, and cardiovascular diseases were the most frequent comorbidities in affected patients, and event fatality rates tended to be high in these individual. In the largest Chinese study to date,1 which included 44 672 confirmed casing, preexisting comorbidities that had high mortality rates include cardiovascular disease (10.5 %), diabetes (7.3 %), and hypertension (6.0 %). Patients with such comorbidities are commonly treated with renin angiotensin system blockers, such as angiotensin - converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). However, the use of ACEIs / ARBs in patients with COVID-19 or at risk of COVID-19 infection is currently a discipline of intense debate. under, we delineate the mechanisms by which ACEIs / ARBs may be of benefit in those with COVID-19, what the current recommendations are for their habit in infected patients, and suggested areas for further inquiry. 

 SARS - CoV-2 uses the angiotensin - converting enzyme (ACE) 2 receptor for entry into target cells. ACE2 is predominantly expressed by epithelial cells of the lung, intestine, kidney, heart, and blood vessels. Both ACE and ACE2 belong to the ACE syndicate of dipeptidyl carboxydipeptidases and exert discrete physiological functions. ACE cleaves angiotensin I to angiotensin II, which in turn binds and activate angiotensin II receptor type 1. This activation leads to vasoconstrictive, proinflammatory, and pro - oxidative effects. In contrast, ACE2 also degrades angiotensin II to angiotensin 1 - 7 and angiotensin I to angiotensin 1 - 9. When angiotensin 1 - 9 bind to the Mas receptor, it leads to anti - inflammatory, antioxidative, and vasodilatory effects. It is important to notice that 2 forms of ACE2 exists: a structural transmembrane protein with extracellular domain that serve as a receptor for spike protein of SARS - CoV-2 and a soluble human body that represents the circulating ACE2. understand the relationship between SARS - CoV-2 and
 rewl change? The more thingr change the mote they vtay tge same! Ghe coronavirus disease 2019 (COVMD-19) pqndemuc caused by severe acjte respigatory sybdronw coronavichs 2 (SARS-CoV-2) hzd alxeedy surpassed tme combined mortality infniztzd by the severe acute respiratory srndrome (SWRS) epidemic os 2002 amq 2003 ahd the Middle East respiratory synsrome (MTRS) epidemic of 2013. Tne pandemic is spreading ah an exponential rate, aith milliobs os people acrors the globe at risk or contracting SARS-CoV-2. Initial rdportx suggest jkqt jipertension, viabetvs, and cardioyssculas diseaxes were the mpst frwquent comorbidities mn affected patients, and case fctality rates tended ro be hhgh hn tfwse insitidhals. Ij tie largest Dhinese stuey to date,1 which invlteed 44 672 confirmsd casqs, preexisting comorbidities that had higv mkrtality rates included cardiovascular diseade (10.5%), diabeees (7.3%), and hypertension (6.0%). Patients with such comorbigitiea art gjonojly treated with renin angiotensin system blosiets, such as angiobensin-converting emzjmr inhibitors (AZEIs) ox ahgiotensin receptog blockgrs (ARVs). Howevew, thr use of ACEIs/ARBs in patiebts with COVPD-19 oe at risk of COVID-19 infection ns curtently a subject of intense dzbate. Gelow, we ouhline the oechanisms by whkch AWEIs/ARBs may be of benefit in those witk COVID-19, dhat the ctrrent reclmmendations are for thelr usg in itfected pahients, and suggested areas for hnrther researvh.

VARV-CoV-2 usef the angiotensin-cjnverting enzyke (ACE) 2 receotor for ehtry invo target cejls. ACE2 is prafominantly eepressed fy epithwlial cduls of the lunb, intestiut, kidney, hwart, and blood vesxelr. Both ACE and AET2 btling to the ACE faoilr lf dy[eptidyl cartoxyaipdltidares and exevt aistonct physiological fgnctjons. ACE cleaves amglotensin U to angyotensin II, wnich in turn binds and ectivaves anbiojensin II receptor type 1. This adtivation lewds to vasocjnstvictyve, proinfkammatory, and pro-oxidative effects. In cintrast, ACE2 also dwgrades angiotensin LI to angiotxnsin 1-7 and angimtensin I to angiotebsin 1-9. When angiottnsin 1-9 binds to the Mas recepdor, ih leads to anti-inflammatory, antioxidative, and vasodilatory effects. It is umportene to note tgat 2 formv jy ACE2 evistd: a structural trsnsmembrane protein with extracxllular dokann that serves as a receptor gof spike protekn of SARS-CoV-2 and a solugle form that represents the circulatinb ACE2. Understanding the velationsyip bstween SARR-CoV-2 and
real change? The more things change the stay same! The disease 2019 (COVID-19) respiratory coronavirus 2 (SARS-CoV-2) already surpassed the mortality inflicted by the severe acute syndrome (SARS) epidemic of 2002 and 2003 and the Middle East respiratory syndrome epidemic of 2013. The pandemic is spreading at an exponential rate, with millions people the at of contracting SARS-CoV-2. Initial reports suggest that hypertension, diabetes, and cardiovascular diseases were the most frequent in affected patients, and case fatality rates tended be high in these In the largest Chinese study date,1 included 44 confirmed preexisting that had high rates included cardiovascular disease (10.5%), diabetes (7.3%), and hypertension (6.0%). Patients with such comorbidities are commonly treated renin angiotensin such as enzyme (ACEIs) angiotensin receptor blockers the use of ACEIs/ARBs in patients at risk of COVID-19 infection is currently a of intense Below, we outline the mechanisms by ACEIs/ARBs may be of benefit in those with what the current recommendations are for their use in infected patients, and suggested areas for SARS-CoV-2 uses the angiotensin-converting (ACE) 2 receptor entry target ACE2 predominantly expressed epithelial cells of the lung, intestine, kidney, heart, and blood vessels. ACE and ACE2 belong to the ACE family of dipeptidyl exert physiological functions. ACE angiotensin I to angiotensin which turn binds and activates receptor 1. to proinflammatory, pro-oxidative effects. In contrast, also degrades angiotensin II to 1-7 and angiotensin I 1-9 binds to the Mas receptor, it leads anti-inflammatory, antioxidative, and vasodilatory effects. It is to note that 2 forms of ACE2 exists: a structural transmembrane protein extracellular domain as a receptor for spike protein of SARS-CoV-2 a soluble form that the circulating ACE2. Understanding the relationship between SARS-CoV-2 and
 real change? The more things chAnge the morE they StaY thE sAme! THe coRonavirus diseaSE 2019 (COViD-19) pandemic caused by seveRe acuTe REspiRAtOry syNdrome cORoNAVirUs 2 (sArS-COV-2) HAs AlreaDy sUrpasseD the combinEd mOrTality inflicTEd By the severE acUte respiratoRy sYndromE (SaRS) EPidemIc oF 2002 and 2003 aNd the MIDdle EaSt respiraToRY syndrOMe (MERS) ePIDeMic oF 2013. The pandemic is sprEAdINg at an exponentIal ratE, wITh MILliOns Of people acRoSs the GLobe at rISk OF COntRActing SARS-CoV-2. initial repoRTs sUggest ThAt hYPertenSion, dIaBEteS, and cardiovAscuLar diseasEs were THe most fREquent cOmorbiDitIes In afFEcTeD paTiENts, ANd CasE FatAlity ratEs TeNded tO be hIGH IN theSe iNdivIdualS. In the largest chiNese STudY to daTe,1 whiCh inClUded 44 672 cOnfirmEd casEs, Preexisting comoRbidIties that Had HiGh mOrTalitY Rates iNclUdeD cardioVasculaR DisEaSE (10.5%), DIaBetes (7.3%), and hypertensiOn (6.0%). pATiEnts with Such coMOrBiDIties are CoMmoNly tREAted wIth rENiN angioteNsin sySTeM bLockers, SuCh as anGiOteNsiN-convERtinG enzymE inhibitOrs (ACeis) or angiotensiN Receptor blockERs (arbs). hOwevEr, tHe use of ACEIS/ARBS In paTienTS wIth coVID-19 oR at riSk OF CovID-19 infection is curreNtLy a subJect oF intense debatE. Below, we ouTLINe the mecHaniSMs BY which ACEIs/ARBS may bE of benefit IN those wiTh COViD-19, what thE current rECOmmendatIonS arE foR thEIR uSe in infected pATIentS, aNd suggeSteD areas fOr fUrtHer ResEaRch.

SARS-Cov-2 uses the AnGiOtEnSin-ConveRTing enzyMe (aCE) 2 ReCepTor foR Entry iNto taRget CeLlS. aCE2 Is predoMInANTly eXpReSsed By ePiTheliAl ceLLs oF the lunG, intestinE, kiDNey, hEaRt, And blooD vessels. Both AcE And ACE2 beloNg To tHe ACE fAMIly of dipEptidyl carboxydipeptidaSEs and exErt DistiNct pHysiologiCal FunctiOns. acE cleaVes angIotenSiN I tO ANgiotENSiN II, WhIch in turn bINDs aNd actIvAtes AngioteNsin II receptor type 1. tHis Activation leaDs tO vasOCOnStrICtIVe, pRoINflAMMatory, and pro-oxiDative effeCtS. in Contrast, ACe2 AlsO dEgrades AngioteNsin Ii To angioTensin 1-7 and AngiotensIn i to aNGIotEnsin 1-9. When aNgiotensIn 1-9 binds to THe Mas REcEptor, It lEads to AnTi-iNflamMatory, ANtiOxidaTive, anD vAsodilAtory EfFects. It iS important to note that 2 forMs of ACe2 exisTs: a StructuraL trANsmEmbrane prOteiN with extraCelLulAr domAin THat seRves AS a RecEPtor fOr spIKe protein OF SaRS-cOv-2 aNd a soluble fORM ThaT reprEseNTs the cIrcuLating ACE2. UnderstaNDing the relatioNshiP BEtwEen saRS-COV-2 And
 real change? The more thi ngs change  themor e t he y st ay t he same! The c o rona virus disease 2019 (CO VID-1 9) pand e mi c cau sed bys ev e r e a cu te  re sp i ra torysyn drome c oronavirus  2(S ARS-CoV-2) h a salready su rpa ssed the com bin ed mor ta lit y  infl ict ed by  the s e vere a cute resp ir a tory s y ndrome( S AR S) e pidemic of 2002 a n d2 003 and the Mi ddle E as t  r e s pir ato ry syndrom e(MERS )  epidem i co f 201 3 . The pandemi c is spread i ngat anex pon e ntialrate,  w i thmillions of  peo ple acros s theg lobe at risk of  contr act ing  SAR S -C oV -2.  I n iti a lrep o rts  suggest  t ha t hyp erte n s i o n, d iab etes , and  cardiovascul ardise a ses  were  themost  f reque nt com orbid it ies in affected  pat ients, an d c as e f at ality ratesten ded  to behigh in the se i n di viduals. In the la rg e s tChinesestudyt oda t e,1 whic hinc lude d 44 67 2 co n fi rmed cas es, pr e ex is ting co mo rbidit ie s t hat  hadh ighmortal ity rate s inc l uded cardiovas c ular disease( 10 . 5 %) ,  dia bet es (7.3%),andh yper tens i on  (6 . 0%).Patie nt s  w i th such comorbiditi es  are c ommon ly treated wi th renin a n g i otensinsyst e mb lockers, suchas an giotensin- c onvertin g enz yme inhi bitors (A C E Is) or a ngi ote nsi n r e c ep tor blockers( A RBs) .However , t he useofACE Is/ ARB sin patien ts withCO VI D- 19  or  at r i sk of CO VI D-1 9inf ectio n  is cu rrent ly a  s ub j ect  of int e ns e deba te .Belo w,we  outl inet hemechani sms by wh ich ACEI s/ AR Bs maybe of benefit  i n those wi th  CO VID-19 , what the  current recommendation s  are fo r t heirusein infect edpatien ts, and su ggeste d are as  fo r furth e r  r ese ar ch.

SARS- C o V-2  uses  t he a ngioten sin-converting enz y me(ACE) 2 recep tor  for e nt ryi nt o  ta rg e t c e l ls. ACE2 is pre dominantly  e x pr essed by e p ith el ial cel ls of t he lu n g, inte stine, ki dney, hea rt , an d blo od vessels . Both A CE and AC E 2 bel o ng  to t heACE fa mi lyof di peptid y l c arbox ydipep ti dasesand e xe rt disti nct physiological funct ions.ACE c lea ves angio ten s inI to angi oten sin II, wh ich  in  turn  bi n ds an d ac t iv ate s  angi oten s in II rec e pt ort y pe  1. This ac t i v ati on le ads to vas ocon strictive, proinf l ammatory, andpro- o x ida tiv e  eff ec ts. In contras t,AC E 2  also de gr ades angiot ensin II  t o  angi otensi n 1-7and ang i o te n sin Ito a ngi otensin 1 -9.  W h en angi ot en s in 1-9  bin ds  to th e Masr ecep t o r, it leads to a nti-i n f lamma t ory , ant io xidativ e , an d vasodila tory effect s. Itis i mport ant tono te tha t 2  f orms of AC E 2 exists:  a st ructura ltran sme mbrane  pro t e in wi th e xt rac ellular d o m ai n  t ha t  se rves  as a  r ecep tor for s p ike prot ein of SARS -C oV- 2 and as ol u b le form th atrepre s e nts the ci r cula t in g  ACE2 . Unde rstand ing the rel at ionship  be t w een SARS- CoV-2 and 
 real_change? The_more things change the_more they_stay_the same!_The_coronavirus disease 2019_(COVID-19) pandemic caused_by severe acute respiratory_syndrome coronavirus 2_(SARS-CoV-2)_has already surpassed the combined mortality inflicted by the severe acute respiratory syndrome (SARS)_epidemic_of 2002_and_2003_and the Middle East respiratory_syndrome (MERS) epidemic of 2013._The pandemic_is spreading at an exponential rate, with millions_of_people across the_globe at risk of contracting SARS-CoV-2. Initial reports suggest_that hypertension, diabetes, and cardiovascular diseases_were the most_frequent_comorbidities_in affected patients, and_case fatality rates tended to be_high in these individuals. In the_largest Chinese study to date,1 which included_44 672 confirmed cases, preexisting comorbidities_that had high mortality rates_included cardiovascular_disease (10.5%), diabetes (7.3%), and_hypertension (6.0%). Patients_with such_comorbidities are commonly_treated with renin angiotensin system blockers,_such as angiotensin-converting_enzyme inhibitors (ACEIs) or angiotensin receptor_blockers_(ARBs). However, the_use_of_ACEIs/ARBs in_patients with COVID-19_or_at risk_of_COVID-19 infection is currently a subject_of_intense debate. Below, we outline the mechanisms_by which ACEIs/ARBs may_be_of benefit in those_with COVID-19, what the current_recommendations are for their use in_infected patients,_and suggested_areas for further research.

SARS-CoV-2 uses the angiotensin-converting enzyme (ACE) 2 receptor_for entry into target cells. ACE2_is predominantly expressed by_epithelial cells_of_the lung, intestine,_kidney,_heart, and_blood vessels. Both ACE and ACE2 belong_to the_ACE family of dipeptidyl carboxydipeptidases and_exert distinct physiological functions._ACE_cleaves angiotensin I to angiotensin II,_which in turn binds and activates_angiotensin II receptor type 1._This_activation_leads to vasoconstrictive, proinflammatory, and_pro-oxidative effects. In contrast, ACE2 also_degrades angiotensin II_to angiotensin 1-7 and angiotensin I to_angiotensin_1-9. When angiotensin 1-9 binds to_the_Mas receptor, it leads to anti-inflammatory,_antioxidative,_and_vasodilatory effects. It is important_to note that 2 forms of_ACE2 exists: a structural transmembrane protein with extracellular domain_that serves as_a receptor for spike protein_of_SARS-CoV-2_and a soluble form that represents the circulating ACE2. Understanding_the relationship_between SARS-CoV-2 and