Angiotensin-Hloov Enzyme Inhibitor Thiab Angiotensin Receptor Blocker Siv Koom Tes Nrog Txo Cov Neeg Tuag Thiab Lwm Yam Kab Mob tshwm sim hauv Asmeskas cov qub tub rog nrog COVID-19

Yog xav paub ntxiv, hu rau:tina.xiang@wecistanche.com

Abstract

Lub hom phiajTxhawm rau txiav txim siab txog kev sib raug zoo ntawmangiotensin-hloov pauv enzymeinhibitors(ACEIs) lossis angiotensin I receptor blockers (ARBs) siv thiab kab mob coronavirus 2019 (COVID-19) qhov hnyav thiab qhov tshwm sim hauv Asmeskas cov qub tub rog.

Cov neeg mob thiab cov txheej txheemPeb rov qab tshuaj xyuas 27,556 tus neeg laus Asmeskas cov qub tub rog uas tau kuaj pom qhov zooCOVID-19Thaum Lub Peb Hlis Ntuj txog Lub Kaum Ib Hlis 2020. Logistic regression thiab Cox cov qauv kev phom sij uas siv cov qhab nia zoo (PS) rau qhov hnyav, kev hloov kho, thiab kev sib txuam tau siv los tshuaj xyuas qhov txawv ntawm ib qho xwm txheej hauv 60 hnub tom qab COVID-19- hnub tim rooj plaub thiab lub sij hawm rau kev tuag, raws li ACEI thiab/los yog ARB tshuaj nyob rau hauv 6 lub hlis ua ntej tus kab mob COVID-19-hnub raug mob.

Cov txiaj ntsigQhov sib tshooj PS hnyav logistic regression qauv qhia qis dua ntawm chav saib xyuas mob hnyav (ICU) nkag (qhov sib txawv piv txwv [OR]95 feem pua ​​​​CI 0.77,0.61-0.98) thiab tuag hauv 60 hnub (0.87,0.{{10}}.97) nrog rau ACEI lossis ARB tshuaj. Cov qub tub rog uas muaj cov tshuaj ARB nkaus xwb kuj muaj qis dua ntawm kev nkag mus rau ICU ({{20}}.64,{25}}44-0.92). Tus qauv sib tshooj PS hnyav zoo ib yam tau pom tias muaj kev pheej hmoo tsawg ntawm lub sijhawm rau tag nrho cov neeg tuag hauv cov qub tub rog nrog ACEI lossis ARB tshuaj (HR [95 feem pua ​​CI]:0.87,0.79-0.97 ) thiab ARB nkaus xwb (0.78,0.{28}}.91). Cov qub tub rog uas muaj daim ntawv tshuaj ACEI muaj qhov sib txawv ntau dua ntawm kev muaj kab mob septic nyob rau hauv 60 hnub tom qab COVID-19- hnub kis tus kab mob zoo (1.22,1.02-1.46).

XausHauv qhov kev tshawb fawb no ntawm ib lub teb chaws pab pawg neeg ntawm Asmeskas cov qub tub rog, peb pom tias kev siv ACEI/ARB hauv cov neeg mob nrog COVID-19 tsis cuam tshuam nrog kev tuag ntau ntxiv thiab lwm yam tshwm sim tsis zoo. Cov kev tshawb fawb yav tom ntej yuav tsum tshuaj xyuas cov hauv paus ntsiab lus thiab paub meej ntxiv txog kev sib raug zoo ntawm ACEI tshuaj nrog sepsis.

Nyem qhov no kom paub ntau ntxiv

1 Kev Taw Qhia

Tus kab mob coronavirus 2019 (COVID-19) kis thoob qhov txhia chaw, tshwm sim los ntawm tus mob hnyav ua pa nyuaj siab corona-virus 2(SARS-CoV-2), tau ua rau muaj kev tsis txaus ntseeg thoob ntiaj teb kev noj qab haus huv thiab nyiaj txiag teeb meem[1,2]. Angiotensin-hloov enzyme inhibitors (ACEIs) thiab angiotensin II receptor blockers (ARBs) yog cov tshuaj siv dav dav uas feem ntau siv los tswj lub plawv tsis ua haujlwm, mob plawv ischemic, kub siab, thiab proteinuria hauv ntshav qab zib thiab mob ntev.mob raum(CKD). Tsis ntev los no, tau muaj kev sib cav ntau txog kev siv ACEIs thiab ARBs hauv cov neeg mob nrog COVID-19, stem-ming los ntawm cov kev tshawb fawb hauv vitro qhia tias ACEIs thiab ARBs txhawb kev qhia ntawm ACE-2[{{3 }}], tus receptor uas SARS-CoV-2 nkag mus rau hauv cov cell [10] hauv qee cov ntaub so ntswg xws li lub plawv thiab lub siab thiab hauv lub raum vasculature [3-8]. Raws li cov kev tshawb fawb no, nws tuaj yeem txiav txim siab tias cov neeg siv ACEI/ARB tuaj yeem muaj kev pheej hmoo ntau ntxiv ntawm SARS-CoV-2 tus kab mob thiab/lossis COVID-19 qhov hnyav [3,5, 11,12]. Txawm li cas los xij, kev tshawb fawb tsis ntev los no hauv nas thiab tib neeg tsis tau lees paub ACE-2 kev tswj hwm los ntawm ACEI/ARB[13-15]. Tsis tas li ntawd, nws tsis paub meej tias kev siv ACEI/ARB puas cuam tshuam nrog kev pheej hmoo ntawm COVID{17}}. Thaum txoj kev tshawb fawb ntawm cov neeg mob ntshav siab los ntawm kev kho mob sib koom ua ke hauv Asmeskas pom tias tsis muaj kev sib koom ua ke ntawm ACEI lossis ARB thiab muaj feem yuav kis tau tus kab mob COVID{18}} [16], lwm txoj kev tshawb nrhiav pom ACEI / ARB siv los cuam tshuam nrog kev nce COVID{ {20}} Kev muaj txiaj ntsig zoo lossis kab mob hnyav hauv cov neeg mob los ntawm cov tsev kho mob pej xeem lossis chaw kho mob sab nraud hauv Hong Kong, txawm tias tom qab hloov kho qhov hloov pauv tsis meej[17].

Kev soj ntsuam thiab kev sim tshuaj tsis ntev los no tau pom cov ntaub ntawv tsis sib haum xeeb ntawm lub luag haujlwm ntawm ACEI/ARB hauv SARS-CoV-2 kev kis tus kab mob lossis qhov hnyav thiab qhov tshwm sim ntawm COVID-19, tab sis feem ntau tsis tau pom qhov tshwm sim tsis zoo [{{3} }].ACE-2, cov enzyme uas hloov angiotensin I mus rau angiotensin II, yog qhia nyob ze ntawm lub ntsej muag ntawm tib neeg epithelial hlwb thoob plaws hauv lub cev, suav nrog lub ntsws [24].ACE-2 kuj tuaj yeem ua rau cov kev hloov pauv ntawm angiotensin II rau angiotensin 1-7 [25], ua rau vasodilation thiabanti-inflammatory, anti-oxidant, thiab anti-apoptotic teebmeem [26].ACEIs thaiv kev tsim ntawm angiotensin I, thaum ARBs inhibit qhov kev txiav txim ntawm angiotensin II ntawm nws cov receptor [5,27,28].

Tsis muaj cov pov thawj muaj zog hauv chav kawm 1 uas txhawb nqa kev txuas ntxiv lossis tsis siv cov tshuaj no, txawm hais tias muaj ntau lub koom haum ua haujlwm nrog rau American Heart Association (AHA), American College of Cardiology (ACC), Heart Failure Society of America (HFSA), thiab European Society ntawm Cardiology (ESC) tau txhawb nqa kev txuas ntxiv ntawm cov neeg ua haujlwm no hauv cov neeg mob uas twb tau muab tso rau ntawm cov neeg ua haujlwm no [29]. Ib yam li ntawd, NIH COVID-19 Pawg Neeg Saib Xyuas Kev Kho Mob tau hais tias cov neeg mob ntawm ACEI lossis ARB rau cov kab mob plawv (lossis lwm yam tsis yog-COVID-19 cov lus qhia) yuav tsum txuas ntxiv cov tshuaj no thaum lub sijhawm tswj hwm tus mob COVID{{5} } tshwj tsis yog kev kho mob qhia (xws li hemodynamic instability)[30]. Qhov kev txiav txim siab no yog los ntawm cov kev tshawb fawb me me los yog hauv kev tshawb fawb ntawm cov pab pawg neeg subpopulation.

Kev koom tes ntawm ACEI/ARB thiab cov txiaj ntsig kev kho mob hauv COVID-19 cov neeg mob tsis tau raug tshuaj xyuas hauv ib pawg loj nrog ntau haiv neeg keeb kwm thiab kev sib txawv. Nyob rau hauv txoj kev tshawb no, siv ib tug loj pawg ntawm cov qub tub rog nyob rau hauv lub Department of Veterans Affairs (VA)COVID-19 Shared Data Resource, uas ubiquitously siv ACEI/ARBs raws li ib feem ntawm lawv kev tswj kab mob, peb nrhiav kev tshuaj xyuas cov teebmeem ntawm ACEI thiab ARB ntawm COVID-19 qhov hnyav thiab qhov tshwm sim.

2 Txoj kev

Txoj kev tshawb no tau tshuaj xyuas los ntawm VA Long Beach Healthcare System's Institutional Review Boards (IRB) thiab pom tau tias raug zam los ntawm kev sau ntawv tso cai vim tias txhua qhov kev ntsuam xyuas tau ua los ntawm kev siv cov ntaub ntawv ua ntej, de-identified. Txoj haujlwm no tau txais kev txhawb nqa los ntawm kev siv cov peev txheej thiab cov chaw ntawm Lub Tsev Haujlwm Saib Xyuas Kev Ua Haujlwm qub tub rog (VA) Kev Tshawb Fawb thiab Kev Sib Txuas Lus (VINCI), VA HSR RES 13-457. Qhov kev tshawb nrhiav no ua raws li cov hauv paus ntsiab lus uas tau teev tseg hauv kev tshaj tawm ntawm Helsinki.

2.1 Kev Tshawb Fawb Cov Neeg thiab Cov Ntaub Ntawv

Peb rov qab tshuaj xyuas cov pab pawg muaj xws li 27,556 tus neeg laus qub tub rog, hnub nyoog siab dua lossis sib npaug li 18 xyoo, nrog rau kev kuaj pom zoo rauCOVID-19nruab nrab Lub Peb Hlis 1st, thiab Kaum Ib Hlis 3rd, 2020. A SARS-CoV-2 quantitative RT-PCR test, ua tau zoo ib yam ntawm txhua qhov chaw VA, tau siv los txiav txim qhov txiaj ntsig zoo COVID-19 kuaj. Hnub tim ntawm qhov ntsuas yog hnub uas SARS-CoV-2 RT-PCR cov txiaj ntsig tau zoo. Cov qub tub rog tau stratified raws li kev siv tshuaj ACEI lossis ARB tsis pub dhau 6 lub hlis ua ntej lawv cov ntaub ntawv COVID{11}} hnub tim. Cov ntaub ntawv hais txog kev siv tshuaj ACEI thiab ARB tau txais los ntawm VA cov lej hauv chav kawm, cov lus piav qhia txog tshuaj, thiab cov npe khoom lag luam los ntawm VA cov ntaub ntawv chaw muag tshuaj. Tag nrho ntawm 7207 tus neeg mob tau pom tias muaj ACEI lossis ARB tshuaj (2678 tus neeg mob ntawm ACE nkaus xwb thiab 4473 tus neeg mob ntawm ARB nkaus xwb, thiab 56 ntawm ob qho tib si) thiab 20,349 tus qub tub rog tsis muaj ACEI lossis ARB tshuaj hauv 6 lub hlis ua ntej lawv rooj plaub. hnub. Cov pab pawg tsis tau tshaj tawm tom kawg no tau siv los ua qhov siv rau txhua qhov kev tshuaj xyuas. Cov ntaub ntawv ntawm lub cev qhov Performance index (BMI), sau tseg hauv 2 xyoo ua ntej hnub ntsuas, cov txiaj ntsig tau tshwm sim hauv 60 hnub ntawm qhov zoo ntawm COVID-19 hnub tim, thiab cov tshuaj tau sau tseg tom qab COVID-19- cov ntaub ntawv zoo yog tau los ntawm VA COVID-19 Cov Ntaub Ntawv Sib Koom. Cov ntaub ntawv ntawm hnub tuag thiab censoring mus txog rau thaum lub Kaum Ib Hlis 30th, 2020, tau txais los ntawm VA mini tseem ceeb cov xwm txheej dataset rau lub sij hawm rau kev tuag qauv.

2.2 Cov Txheej Txheem Txheej Txheem

Cov yam ntxwv hauv paus tau stratified raws li ACEI lossis ARB siv. Cov yam ntxwv tau tshaj tawm raws li qhov txhais tau tias ± tus qauv sib txawv (SD) rau qhov sib txawv tsis tu ncua lossis feem N (feem pua) rau qhov sib txawv categorical. Ob pawg tau muab piv nrog kev xeem ntawm qhov kev xeem los yog chi-squared qhov tsim nyog rau hom sib txawv thiab kev faib tawm.

Tus qauv logistic regression tau siv los tshuaj xyuas kev sib raug zoo ntawm ACEI lossis ARB, ACEI nkaus xwb, thiab ARB tsuas yog siv tsis tau ACEI / ARB siv nrog cov txiaj ntsig ntawm kev siv tshuab ua pa, mus pw hauv tsev kho mob, chav saib xyuas mob hnyav (ICU), mob ua pa tsis ua haujlwm, mob hnyav. myocardial infarction (MD), mob raum mob (AKD), mob ntsws, mob sepsis, thiab tuag nyob rau hauv 60 hnub tom qab tus kab mob COVID-19-cov ntaub ntawv zoo (ACEI nkaus xwb thiab ARB nkaus xwb tsom xam txhua tus tsis suav nrog 56 tus neeg mob uas tau noj tshuaj ob leeg. ). Ib qho Kaplan-Meier nrog kev ntsuas ntsuas ntsuas thiab Cox cov qauv kev pheej hmoo ntawm kev pheej hmoo rov qab tau siv los tshuaj xyuas kev sib raug zoo ntawm ACEI lossis ARB, ACEI nkaus xwb, thiab ARB tsuas yog tsis muaj ACE lossis ARB siv nrog cov txiaj ntsig ntawm lub sijhawm tuag. Lub sijhawm taug qab tau suav los ntawm COVID-19- hnub kis tus kabmob zoo mus txog rau hnub tuag, ploj mus tom qab, lossis hnub kawg ntawm lub sijhawm kawm ntawm lub Kaum Ib Hlis 30, 2020. Cov kev xav zoo sib xws rau Cox feem cuam tshuam regression raug soj ntsuam siv Kaplan-Meier ciaj sia taus nkhaus (Ntxiv Fig. 1) thiab tsis zoo log-log plots. Rau ob qho tib si logistic thiab Cox qhov kev pheej hmoo ntawm kev pheej hmoo rov qab, tus qauv tsis hloov kho tau tsim nrog rau cov qauv hloov kho uas suav nrog cov kev hloov pauv ntawm lub lim tiam thiab VA chaw nres tsheb ntawm COVID-19 hnub, hnub nyoog, poj niam txiv neej, haiv neeg, haiv neeg, Kev haus luam yeeb, comorbid MI, congestive heart failure (CHF), peripheral arterial dis-ease (PAD), kab mob plawv, cerebrovascular dis-ease, chronic obstructive pulmonary disease (COPD), AKI, CKD, kab mob siab, ntshav qab zib, kub siab, mob cancer. , AIDS, thiab Charlson Comorbidity Index (CCD)[31]. Lwm yam tseem ceeb suav nrog BMI ntawm hnub tim; Cov tshuaj tau sau tseg hauv 2 xyoos ua ntej hnub kawg, suav nrog metformin, calcium channel blockers (CCB), statins, beta-blockers; thiab kawg cov tshuaj tau sau tseg tom qab hnub rooj plaub, suav nrog azithromycin, remdesivir, hydroxychloroquine, thiab dexamethasone.

Txhawm rau hais txog qhov muaj peev xwm ntawm kev tsis ncaj ncees thiab kev tsis sib haum xeeb los ntawm kev qhia, qhov kev txheeb xyuas qhov zoo (PS) tau ua. Qhov xwm txheej yuav tshwm sim ntawm kev noj ACEI lossis ARB, ACEI nkaus xwb, lossis ARB nkaus xwb tau kwv yees siv cov qauv sib txawv ntawm cov logistic regression, uas suav nrog txhua qhov hloov pauv siv rau kev hloov kho tus qauv raws li tau hais dhau los thiab PS tau suav. Qhov kev txheeb xyuas PS suav nrog peb tus qauv: thawj qhov uas cov qub tub rog tau sib tw {{{0}}} rau-1 ntawm lawv qhov kwv yees PS, qhov thib ob uas PS tau suav nrog qhov sib txawv hauv cov qauv hloov kho, thiab thib peb txoj kev sib tshooj PS qhov hnyav qhov twg txhua tus qub tub rog hnyav sib npaug rau qhov tshwm sim ntawm qhov sib txawv ntawm pawg [32,33]. Cov qub tub rog tau sib koom ua ke siv txoj kev sib tw ib-rau-ib-ib-rau-ib-ib-rau-ib greedy txuam nrog lub caliper dav ntawm 0.2 SDs yam tsis hloov. Ntawm PS-matched cohort, tus qauv sib txawv rau qhov sib tw ACEI lossis ARB siv thiab cov pab pawg tsis siv tau raug xam rau txhua qhov sib txawv los sib piv qhov ua tiav ntawm kev sib tw. Peb tau txiav txim siab qhov sib txawv ntawm tus qauv ntau dua 0.2 los ua qhov tseem ceeb. Peb qhov sib txawv logistic regression qauv thiab Cox proportional hazards regression qauv tau rov qab ua dua nyob rau hauv PS-matched cohort, nrog PS raws li kev hloov pauv, thiab hnyav los ntawm kev sib tshooj PS.

Ib pab pawg neeg tsom xam kuj tau ua nyob rau hauv uas cov qub tub rog tau muab faib ua pawg raws li seb lawv puas muaj comorbid ntshav siab. Los ntawm pawg neeg mob ntshav siab, ib pab pawg thib peb tau tsim rau cov neeg mob ntshav siab tab sis tsis muaj ntshav qab zib, CKD, lossis mob plawv tsis ua haujlwm. Ntawm peb pawg neeg no, ib qho kev sib tshooj PS hnyav logistic regression qauv tau ua piv txwv qhov txawv ntawm ntau qhov tshwm sim hauv 60 hnub tom qab hnub sib piv ACEI lossis ARB siv piv tsis siv ACEI / ARB. Kev hloov pauv ntawm kev kub siab ntawm kev sib koom ua ke ntawm ACEI lossis ARB siv nrog qhov sib txawv ntawm ib qho kev tshwm sim tau raug tshuaj xyuas hauv pawg pab pawg thiab siv Wald's test rau kev sib cuam tshuam.

Ib qho kev soj ntsuam pab pawg ntxiv kuj tau ua piv txwv Dub piv rau cov qub tub rog uas tsis yog Dub. Qhov sib tshooj PS hnyav logistic regression qauv tau rov ua dua ntawm ob pawg sub. Kev hloov pauv ntawm haiv neeg ntawm kev sib raug zoo ntawm ACEI lossis ARB siv nrog qhov sib txawv ntawm qhov kev tshwm sim tau raug tshuaj xyuas siv Wald qhov kev sim rau kev sib cuam tshuam. Cov ntaub ntawv ntawm BMI tau ploj lawm nyob rau hauv kwv yees li 3 feem pua ​​​​ntawm cov qub tub rog thiab tau ua haujlwm siv imputation los ntawm txhais tau tias. Cov ntaub ntawv rau tag nrho lwm yam hloov pauv tau ua tiav. Txhua qhov kev ntsuam xyuas tau ua nrog SAS Enterprise Guide, version7.1 (SAS Institute Inc., Cary, NC).

3 Kev tshwm sim

3.1 Demographics thiab Comorbidities

Ntawm 27,556 COVID-19- cov qub tub rog zoo, qhov nruab nrab ± SD hnub nyoog ntawm tag nrho cov qub tub rog yog 63 ± 16 xyoo, 12 feem pua ​​​​yog poj niam, 62 feem pua ​​​​yog Dawb, 26 feem pua ​​​​ Dub, thiab 10 feem pua ​​​​hais lus Mev. Ntawm tag nrho cov COVID-19- cov qub tub rog zoo, cov comorbidities uas muaj ntau tshaj plaws yog kub siab (62 feem pua), ntshav qab zib (37 feem pua), thiab kab mob plawv (33 feem pua). Ntawm 20,349 tus qub tub rog uas tsis muaj ACEI lossis ARB tshuaj, qhov nruab nrab ± SD hnub nyoog yog 61 ± 18 xyoo, 14 feem pua ​​​​yog poj niam, 61 feem pua ​​​​yog Dawb, 25 feem pua ​​​​yog Dub, thiab 10 feem pua ​​​​hais lus Mev, 51 feem pua ​​​​hnyav, 28 feem pua. mob ntshav qab zib, thiab 28 feem pua ​​​​tau mob plawv tsis yooj yim. Piv nrog rau cov qub tub rog uas tsis muaj ACEI / ARB, cov neeg uas muaj ACEI / ARB yog cov laus dua, tsis tshua muaj poj niam lossis neeg Mev, feem ntau yuav yog Dawb lossis Dub, thiab feem ntau yuav muaj ze li ntawm txhua qhov kev sib txuam nrog kev zam ntawm AIDS (Table 1 ). Cov yam ntxwv hauv paus hauv ib-rau-ib PS-match cohort tau sau tseg hauv Cov Lus Ntxiv 1.

3.2 Qhov Tseem Ceeb Ntawm Cov Tau Txais 60 Hnub Tom Qab-COVID-19- Hnub Kawg Rau ACEI/ARBUse piv rau Tsis Siv

Nyob rau hauv tus qauv logistic regression tsis kho, cov qub tub rog nrog ACEI lossis ARB siv tau muaj qhov sib txawv ntau dua ntawm kev muaj xwm txheej rau kev siv tshuab ua pa, pw hauv tsev kho mob, ua pa tsis ua haujlwm, mob MI, AKI, mob ntsws, mob ntsws, thiab tuag hauv 60 hnub tom qab kuaj pom muaj tus kab mob COVID-19(Table 2). Txawm li cas los xij, cov koom haum tau txo qis rau qhov tsis muaj txiaj ntsig rau txhua qhov txiaj ntsig nrog kev zam ntawm kev tuag hauv cov qauv suav nrog covariates (hloov, PS kho, PS matched, thiab sib tshooj PS hnyav). Tus qauv PS sib tshooj pom tau tias ACEI lossis ARBuse muaj 13 feem pua ​​​​ntawm cov neeg tuag tsawg dua hauv 60 hnub ntawm COVID-19 hnub tim (OR[95 feem pua ​​​​CI 0.87,0 }. nyob rau hauv 60 hnub ntawm COVID-19 rooj plaub (OR [95 feem pua ​​​​CI 0.77,0.61-0.98,p=0.0309] rau qhov sib tshooj PS hnyav qauv).

Thaum muab piv ACEI tsuas yog tsis siv ACEI, nyob rau hauv cov qauv sib tshooj PS hnyav, muaj qhov sib txawv ntau dua ntawm kev muaj tus kab mob septic 60 hnub tom qab COVID-19- hnub teeb pom kev zoo rau cov neeg siv ACEI (OR [95 feem pua ​​​​CI 1.22 , 1.02-1.46], p=0.0283) thiab cov txiaj ntsig tau tsis zoo rau tag nrho lwm cov txiaj ntsig (Table 3).

Thaum muab piv ARB tsuas yog tsis siv ARB, hauv cov qauv PS sib tshooj, cov txiaj ntsig tau pom qhov tsis sib xws ntawm ICU qhov xwm txheej lossis kev tuag hauv 60 hnub tom qab COVID-19 hnub tim rau cov neeg siv ARB piv rau cov tsis siv. (OR [95 feem pua ​​CI 0.64, 0}44-0.92], p=0.0153, thiab 0.78,0.{{ 14}}.91,p=0.0022 rau ICUevent, thiab kev tuag, feem).

Ntawm 27,556 COVID-19- cov qub tub rog zoo, 17,188 (62 feem pua ​​​​tau kuaj pom tias muaj ntshav siab, ntawm 10,335(60%) tsis muaj ACEI lossis ARB tshuaj thiab 6853 (40 feem pua ​​) puas tau muaj ACEI lossis ARB tshuaj nyob rau hauv 6 lub hlis ua ntej lawv hnub rooj plaub. Yog li ntawd, ib pawg neeg soj ntsuam tau ua piv txwv ACEI lossis ARB siv piv rau cov tsis siv ntawm cov neeg mob ntshav siab thiab cov uas tsis muaj ntshav siab (Table 2). Los ntawm pawg neeg mob ntshav siab, ib pab pawg ntxiv tau txheeb xyuas saib cov neeg mob ntshav siab tsis muaj ntshav qab zib, plawv tsis ua hauj lwm, lossis CKD. Cov qauv sib tshooj PS hnyav logistic regression tau pom tias cov qub tub rog kub siab nrog ACEI lossis ARB siv. muaj qhov tsawg dua ntawm kev mus ntsib ICU lossis tuag tsis pub dhau 60 hnub tom qab lawv hnub rooj plaub (OR [95 feem pua ​​CI0.70.0.55-0.89], p=0.0041, thiab 0.82,0. Muaj kev pheej hmoo siab dua ntawm kev mus pw hauv tsev kho mob, mus ntsib ICU, mob ua pa tsis ua haujlwm, AKI, mob ntsws, mob sepsis, lossis kev tuag tshwm sim 60 hnub tom qab lawv COVID-19- hnub kis tus mob zoo. Rau cov neeg noj ACEI lossis ARB cov tshuaj uas muaj ntshav siab tab sis tsis muaj ntshav qab zib lossis lub plawv tsis ua haujlwm, cov txiaj ntsig tsis tseem ceeb rau qhov tshwm sim. Wald qhov kev sim rau kev sib cuam tshuam ntawm pawg neeg raug thiab kub siab yog qhov tseem ceeb rau cov txiaj ntsig ntawm kev mus pw hauv tsev kho mob, ICU mus ntsib, mob ua pa tsis ua haujlwm, AKI, mob ntsws, sepsis, thiab tuag hauv 60 hnub qhia tias cov teebmeem ntawm ACEI lossis ARB siv rau qhov txawv ntawm cov no. Cov txiaj ntsig tau sib txawv ntawm cov neeg mob ntshav siab piv rau cov uas tsis muaj (Cov Lus Qhia Ntxiv 2).

Ib qho kev soj ntsuam pab pawg ntxiv tau ua piv txwv ACEI lossis ARB siv cov tub rog Dub thiab tsis yog Dub. Ntawm cov qub tub rog uas tsis yog Dub, qhov sib tshooj PS hnyav logistic regression qauv qhia tau hais tias tsis muaj kev tuag tsawg dua li ntawm 60 hnub tom qab COVID-19- hnub kis tus kab mob zoo (OR [95 feem pua ​​​​CI 0}.82 ,0.72-0.92],p{10}}.0012)(Table 3). Rau cov qub tub rog Dub, tag nrho cov koom haum tsis yog lawm. Wald qhov kev sim rau kev sib cuam tshuam ntawm ACEI lossis ARB siv thiab Dub piv rau cov pab pawg uas tsis yog Dub yog qhov tseem ceeb rau kev tuag nyob rau hauv 60 hnub txij li hnub cov ntaub ntawv zoo (p =0.0276)(Table 3).

3.3 Kev pheej hmoo rau kev tuag tom qab-COVID-19- Hnub Kawg rau ACEl lossis ARB Siv thiab Tsis Siv

Kaplan-Meier (Ntxiv daim duab. 1) thiab kev txheeb xyuas cov qhab-nees uas siv qhov sib tshooj PS qhov hnyav tau pom qhov sib txawv tseem ceeb ntawm pawg raug (p =0.{{10}}027 ). Hauv Cox cov qauv kev phom sij uas ntsuas lub sij hawm rau kev tuag, tus qauv tsis hloov kho tau pom tias muaj kev sib koom ua ke ntawm ACEI / ARB kev siv thiab kev pheej hmoo ntawm txhua qhov kev tuag, uas tseem zoo ib yam tom qab hloov kho covariates. Tom qab ib-rau-ib PS sib piv, cov neeg siv ACEI lossis ARB muaj qhov pheej hmoo ntawm kev tuag tom qab COVID-19 kuaj mob (HR [95 feem pua ​​​​CI {{20}}}.82({{ 28}}.74-0.91],p=0. feem pua ​​CI0.87,0.79-0.96],p=0.0075) thiab tom qab sib tshooj PS qhov hnyav (HR [95 feem pua ​​CI0.87, 0.{29} }.96],p=0.0051).Thaum muab piv lub sij hawm rau kev tuag ntawm cov neeg siv ACEI piv rau cov neeg tsis siv, qhov txo qis ntawm kev pheej hmoo tuag tau pom tsuas yog hauv PS ib-rau-ib tus qauv sib tw (HR [ 95 feem pua ​​​​CI 0.83,0. rau-ib qho qauv sib tw, tus qauv nrog cov kev hloov kho rau PS, thiab tseem nyob rau hauv qhov sib tshooj PS hnyav qauv (HR [95 feem pua ​​​​CI 0.78,0.68-0.91], p=0.001 ) (Table 5).

4 Kev sib tham

Txawm hais tias muaj ntau qhov kev tshawb fawb rov qab tsis ntev los no uas tau tshuaj xyuas lub koom haum ntawm ACEI / ARB kev kho mob ntawm cov txiaj ntsig ntawm cov neeg mob uas muaj tus kab mob SARS-CoV2[1,20,34-39], kev siv cov tshuaj no rau cov neeg mob uas muaj kev pheej hmoo rau SARS-CoV{ {6}} cov teeb meem tseem muaj teeb meem. Peb txoj kev tshawb fawb hauv 27,556 tus qub tub rog tau pom tias kev kho ACEI / ARB tsis cuam tshuam nrog ntau dua ntawm qhov tshwm sim tsis zoo hauv cov neeg mob nrog COVID-19; Qhov tseeb, peb tus qauv PS-match tau pom qhov txo qis ntawm kev tuag nrog ACEI / ARB siv. Txawm li cas los xij, kev siv ACEI tau cuam tshuam nrog kev nce ntxiv ntawm sepsis ntawm cov neeg mob COVID{11}}.

Peb qhov kev tshawb pom tau zoo ib yam nrog cov ntawv tshaj tawm dhau los, uas tseem tau sau tseg qhov txo qis ntawm kev pheej hmoo ntawm cov teeb meem thiab kev tuag ntawm cov neeg mob nrog COVID-19 uas tau kho nrog ACEI/ARB [20-23,40-43]. Ib txoj kev tshawb fawb ntau hauv 1128 cov neeg laus uas muaj ntshav siab kuaj pom nrog COVID 19 pom tias kev siv ACEIs / ARBs cuam tshuam nrog kev pheej hmoo tsawg dua ntawm txhua qhov kev tuag thaum piv nrog cov neeg tsis siv [20]. Qee qhov kev tshuaj ntsuam meta pom tau tias kev siv ACEI/ARB cuam tshuam nrog kev txo qis ntawm COVID-19 tsis yooj yim thiab kev tuag [21-23, 40]. Piv txwv li, random-effects meta-analysis ntawm 26 cov kev tshawb fawb uas muaj 8104 ACEI / ARB cov neeg siv thiab 8203 cov neeg mob uas tsis siv ACEIs / ARBs tau qhia tias kev kho ACEI / ARB cuam tshuam nrog kev pheej hmoo tsawg dua ntawm kev tuag nyob rau hauv kev mob siab rau COVID{18. }} neeg mob [41].

Thaum cov kev tshawb fawb saum toj no tau qhia txog kev txo qis hauv kev tuag hauv COVID-19 cov neeg mob uas siv ACEI/ARB, lwm cov kev tshawb fawb pom tias tsis muaj kev sib raug zoo ntawm cov hloov pauv no [35,37,44,45]. Khera et al tau qhia tias kev siv ACEI/ARB tsis cuam tshuam nrog kev pheej hmoo ntawm kev mus pw hauv tsev kho mob lossis cov neeg mob tuag hauv cov neeg mob hauv PS-match nrog cov neeg mob sab nraud ntawm 2263 tus neeg mob uas muaj keeb kwm mob ntshav siab nrog rau qhov zoo SARS-CoV-2 kuaj, thiab ib pawg neeg kho mob hauv tsev kho mob ntawm 7933 hauv tsev kho mob COVID-19 cov neeg mob [44]. Tsis tas li ntawd, ib qho kev tshawb fawb ib leeg ntawm 1178 COVID{14}} cov neeg mob hauv tsev kho mob hauv Wuhan, Tuam Tshoj tau qhia tias kev siv ACEI/ARB hauv 115 ntawm 362 tus neeg mob ntshav siab tsis cuam tshuam nrog COVID-19 qhov hnyav lossis kev tuag. [37]. Qhov tsis sib xws ntawm peb qhov kev tshawb pom thiab cov ntawv ceeb toom no yuav yog vim lawv cov qauv me me thiab cov neeg mob tsawg uas siv ACEIs / ARBs. Peb qhov kev tshawb fawb loj ntawm cov qub tub rog suav nrog ~ 60 feem pua ​​​​cov neeg mob ntshav siab thiab 26 feem pua ​​​​cov neeg siv ACEI / ARB. Txoj kev tshawb no tau pom nyob rau hauv qhov sib tshooj PS hnyav logistic regression qauv uas ACEI / ARB siv txo qhov tsis sib xws ntawm ICUevent thiab kev tuag.

Peb lub koom haum tshawb fawb suav nrog 26 feem pua ​​​​cov neeg mob Dub uas muaj qhov tshwm sim ntau dua ntawm COVID-19 thiab muaj feem cuam tshuam rau kev tuag thaum piv rau lwm haiv neeg [46,47]. Peb pom tias ACEI/ARB siv txo qis kev tuag ntawm cov qub tub rog uas tsis yog Dub nrog COVID-19 tab sis tsis nyob hauv lawv cov neeg Dub. Cov neeg dub muaj kev pheej hmoo siab kub siab, kab mob plawv, ntshav qab zib, kab mob raum, thiab muaj qhov sib txawv ntawm cov lus teb rau kev kho mob [48-57]. Qhov hnyav dua ntawm comorbidities thiab txo cov lus teb rau ACEIs / ARBs hauv cov pej xeem no tuaj yeem piav qhia qhov sib txawv ntawm kev pheej hmoo tuag nrog ACEI / ARBuse ntawm cov neeg mob Dub thiab tsis yog Dub. Txawm li cas los xij, kev tshawb fawb yav tom ntej yuav xav tau los tshuaj xyuas cov kev tshawb pom no ntxiv.

Lub hnub nyoog nruab nrab ntawm SARS-CoV-2-cov neeg siv ACEI/ARB zoo hauv peb txoj kev tshawb fawb yog 68 xyoo. Ntau tus neeg mob no muaj lwm yam mob xws li ntshav siab (62 feem pua), ntshav qab zib (37 feem pua), kab mob plawv (33 feem pua), thiab mob ntsws (16 feem pua) thiab kab mob raum (15 feem pua), uas tau pom tias ua rau muaj kev pheej hmoo rau COVID-19- cuam tshuam txog cov teeb meem thiab kev tuag [46,{11}}]. Txawm li cas los xij, peb txoj kev tshawb fawb qhia tau tias kev siv ACEI/ARB hauv COVID-19 cov neeg mob tsis cuam tshuam rau qhov tshwm sim ntawm tus kab mob thiab qhov tseeb tuaj yeem ua rau txo qis COVID{13}} cuam tshuam txog kev tuag ntawm cov neeg tsis yog Dub. Cov kev tshawb pom no yuav muaj qhov cuam tshuam ncaj qha rau cov neeg mob laus thiab cov neeg uas muaj cov kab mob ntev ntev hauv cov pej xeem Asmeskas.

Ib qho kev pom zoo ntawm peb txoj kev tshawb fawb yog tias ACEIuse tau cuam tshuam nrog kev nce ntxiv ntawm sepsis ntawm COVID-19 cov neeg mob. Cov kev tshawb pom no tau pom zoo nrog kev tshawb fawb tsis ntev los no ntawm 2700 tus neeg mob tau txais mus rau ICU thaum lub Ib Hlis 2008 thiab Kaum Ob Hlis 2015 hauv Sweden uas pom muaj kev koom tes ntawm ACEI / ARBuse thiab sepsis [64]. Peb tsis pom muaj kev koom tes ntawm ARB siv ib leeg thiab sepsis. Cov kev tshawb fawb yav dhau los hauv COPD thiab cov neeg mob ntshav siab tau pom tias cov neeg siv ACEI muaj kev pheej hmoo siab ntawm sepsis ntau dua li cov neeg siv ARB [65,66]. Muab hais tias ARBs tau pom tias txhim kho o, lawv tuaj yeem txo qhov kev pheej hmoo ntawm sepsis [67-70]. Tsis zoo li ACEIs, ARBs muaj ob lub luag haujlwm hauv kev tswj kev mob (Fig.2); ARBs inhibit vasoconstriction thiab pro-inflammatory teebmeem ntawm angiotensin II los ntawm thaiv AT, receptor activation, thiab ntawm qhov tod tes, lawv kho cov vasodilation thiab anti-inflammatory teebmeem los ntawm kev ua kom AT, receptors thiab Mas receptors [25,71, 72] . Hauv qhov xwm txheej kawg, ARBs ua rau muaj kev tawm tswv yim nce hauv angiotensin Il uas tuaj yeem khi rau AT, receptors ncaj qha lossis tuaj yeem hloov los ntawm ACE2 rau hauv angiotensin (1-7) uas tuaj yeem khi rau Mas receptor thiab kho vasodilation thiab tiv thaiv. inflammatory teebmeem [25,71,72]. Cov kev tshawb fawb ntxiv yog xav tau kom paub meej thiab tshawb xyuas cov txheej txheem hauv qab no rau kev tshawb pom.

ACEIs / ARBs tau siv dav hauv kev kho mob ntshav siab, kab mob plawv, thiab ntshav qab zib nephropathy. Raws li cov kev tshawb fawb yav dhau los uas tau qhia txog kev txhim kho ntawm ACE2 hauv vasculature ntawm nas los ntawm kev kho mob nrog supra-pharmacologic koob tshuaj ACEIs / ARBs [3-8], nws tau tshaj tawm tias kev siv ACEI / ARB tuaj yeem ua rau muaj kev pheej hmoo ntawm COVID{{3} }} mob hnyav hauv cov neeg mob. Txawm li cas los xij, ob peb qhov kev tshawb fawb tsis ntev los no hauv tib neeg thiab tsiaj cov qauv tsis pom ACE2 upregulation nrog ACEI/ARBs[13-15]. Ramchand li al, thaum tshawb xyuas lub luag haujlwm ntawm kev ncig ACE2 qib thiab cov xwm txheej tsis zoo ntawm cov hlab plawv hauv cov neeg mob uas muaj kab mob plawv, pom tias kev siv ACEI / ARB tsis nce qib ACE2 [13]. Burrell thiab al tshuaj xyuas ACE2 qhia tom qab MI hauv nas thiab pom tias ACEI'ramipril' tsis muaj kev cuam tshuam rau lub plawv ACE2 mRNA qhia[14]. Kev tshawb fawb tsis ntev los no hauv tus qauv nas tau pom tias ACEI 'captopril thiab ARB 'telmisartan tsis nce ACE2 hauv lub ntsws lossis lub raum epithelia uas yog lub hom phiaj rau SARS-CoV-2 kab mob [15]. Cov kev tshawb fawb no txhawb peb qhov kev tshawb pom tias kev siv ACEI / ARBs tsis ua rau muaj kev pheej hmoo ntawm qhov tshwm sim tsis zoo. Tsis tas li ntawd, kev tshawb fawb tsis ntev los no hauv cov qauv kev sim ntawm cov mob ntsws mob hnyav, suav nrog tus qauv ntawm SARS-CoV-2 kis kab mob, qhia tias ARBs tuaj yeem txo cov teeb meem COVID{18}} los ntawm kev txo qis Ang II-mediated mob ntsws mob los ntawm kev thaiv. TSI 1R [73]. Cov no yog qee cov txheej txheem muaj peev xwm uas tuaj yeem cuam tshuam qhov txo qis ntawm COVID{22}} tus neeg tuag uas peb tau pom hauv ACEI/ARB cov neeg siv hauv peb qhov kev tshuaj ntsuam. Tsis tas li ntawd, statins, nrog rau lawv cov cholesterol-txo cov teebmeem, tiv thaiv kab mob, immunomodulatory thiab tshuaj tua kab mob tuaj yeem yog lawv tus kheej lossis ua ke nrog ACEI / ARB tuaj yeem hloov kho COVID{25}} kev tuag [74-77].

Lub zog ntawm txoj kev tshawb no suav nrog cov qauv loj loj, siv VA Observational Medical Outcomes Partnership cov ntaub ntawv nrog rau cov kev tshawb pom muaj zog thoob plaws ntau yam qauv. Cov kev tshawb fawb yav dhau los uas tshuaj xyuas kev koom tes ntawm ACEI/ARB siv nrog COVID-19 cov txiaj ntsig tau raug txwv los ntawm kev muaj cov pab pawg me me. Txoj kev tshawb no muaj cov qauv loj ntawm 27,556 tus neeg mob thiab suav nrog kev hloov kho dav dav rau cov teeb meem tsis meej pem. Cov neeg mob VA, uas suav nrog feem ntau ntawm cov neeg mob laus uas muaj ntau yam kab mob sib kis, kuj tseem tsim nyog rau kev tshuaj xyuas qhov cuam tshuam ntawm ACEI/ARB hauv cov pab pawg muaj kev pheej hmoo siab tshaj plaws rau COVID-19. Txawm li cas los xij, cov neeg sau ntawv kuj xav sau ntau qhov kev txwv ntawm txoj kev tshawb no. Txawm hais tias muaj kev hloov kho dav dav rau cov kev hloov pauv hauv qhov kev soj ntsuam kev tshawb fawb no, peb tsis tuaj yeem txiav txim siab qhov seem ntawm qhov tsis sib haum xeeb lossis ua qhov kev txiav txim siab. Peb tsis tuaj yeem hloov kho rau lwm tus muaj peev xwm ua tsis tau xws li cov cim ntawm COVID-19 kab mob hnyav xws li mob cytokines. Peb lub hauv paus rau cov ntaub ntawv raug thiab cov txiaj ntsig tau yog cov ntaub ntawv kho mob hauv hluav taws xob, thiab tseem muaj feem cuam tshuam los yog qhov tshwm sim tsis raug. Thaum kawg, peb cov txiaj ntsig yuav tsis tuaj yeem ua rau cov pej xeem dav dav vim tias peb pawg neeg muaj cov neeg mob VA uas feem ntau yog cov txiv neej laus.

Xaus 5

Peb txoj kev tshawb fawb ntxiv qhia tias ACEIs thiab ARBs muab cov txiaj ntsig muaj zog dual, tsis yog hauv kev tiv thaiv thiab kho cov kab mob plawv nkaus xwb tab sis kuj yog cov tshuaj tiv thaiv kab mob thiab cov kab mob immunomodulatory [78]. Peb qhov kev tshawb pom tau ua raws li cov lus pom zoo ntawm ntau lub koom haum kev tshaj lij thiab NIH COVID-19 Cov Lus Qhia Txog Kev Kho Mob uas txhawb nqa kev txuas ntxiv ntawm ACEI thiab ARBs hauv cov neeg mob uas tam sim no tau sau cov neeg ua haujlwm zoo li no, txiav txim siab tias cov neeg mob uas muaj kab mob plawv muaj kev pheej hmoo siab ntxiv. ntawm tus mob hnyav COVID-19 [79]. Kev sim tshuaj kho mob tseem yuav yog qhov tseem ceeb hauv kev tshuaj xyuas qhov cuam tshuam ntawm kev siv ACEI / ARB ntawm cov txiaj ntsig kho mob hauv cov neeg mob COVID. Cov txiaj ntsig ntawm de novo ACEI/ARB siv hauv COVID-19 cov neeg mob kuj tseem muaj txiaj ntsig rau kev kawm ntxiv.

Cov ntaub ntawv

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