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PART Ⅱ: SARS-CoV-2 Kev kis kab mob hauv Syrian Hamster Model ua rau mob ib yam li hom I Interferon Dysregulation hauv ob qho tib si ua pa thiab tsis ua pa nrog rau lub plawv thiab raum.

Mar 18, 2022

Yog xav paub ntxiv:ali.ma@wecistanche.com



Magen Ellen Francis, Una Goncin & et al.

NYEM QHOV NO RAU PART Ⅰ


Abstract

COVID-19(tus kab mob coronavirus 2019) los ntawmSARS-CoV-2(mob hnyav ua pa syndrome coronavirus 2) kab mob yog ib yam kab mob cuam tshuam rau ntau lub hauv nruab nrog cev. Tus qauv uas ntes tag nrho cov tsos mob ntawm kev kho mobCOVID-19, nrog rau cov kab mob ntev-hauler, xav tau. Peb tau tshawb xyuas tus tswv teb cov lus teb cuam tshuam nrog kev kis kab mob hauv ntau lub cev hauv nruab nrog cev nrog rau cov kab mob ua pa, lub plawv, thiablub raumtom qabSARS-CoV-2kis mob hauv Syrian hamsters. Peb pom muaj qhov nce ntxiv hauv cov cytokines inflammatory (IL-6, IL-1beta, thiab TNF) thiab hom II interferons qhov twg hom I interferons tau inhibited. Kev soj ntsuam ntawm cov ntaub so ntswg extrapulmonary qhia tau hais tias mob hauv lub cevraum, daim siab, thiab lub plawv uas tseem tsis muaj hom I interferon upregulation. Histologically, lub plawv muaj pov thawj ntawm myocarditis thiab microthrombi thaum lubraummuaj tubular o. Cov txiaj ntsig no muab kev nkag siab rau cov kab mob ntau yam kab mob uas tau ntsib los ntawm cov neegCOVID-19thiab tej zaum tus kab mob ntev nyob rau hauv cov neeg nrog post-acute sequelae ntawmSARS-CoV-2(PASC). Tus mob coronavirus 2) kev kis kab mob tuaj yeem cuam tshuam rau ntau lub hauv nruab nrog cev nrog rau cov kab mob ua pa, kab mob urinary, neurological system, thiab kab mob plawv. Yuav kom tsim nyog kawm txog tus kab mob no thiab ntsuas kev kho mob, ib qho qauv uas ntes tag nrho cov tsos mob ntawm kev kho mobCOVID-19yog yuav tsum tau. Nws paub tias kev puas tsuaj uas tshwm sim tom qab kis kab mob feem ntau yog vim tus tswv tsev lub cev tiv thaiv kab mob. Yog li ntawd, ntawm no peb tau tshawb xyuas seb lub cev tiv thaiv kab mob cov lus teb tau tswj hwm li cas hauv ntau lub hauv nruab nrog cev nrog rau cov kab mob ua pa, lub plawv, thiablub raumtom qabSARS-CoV-2kis mob hauv Syrian hamsters. Peb pom muaj kev nce ntxiv hauv cytokines inflammatory (IL-6, IL-1beta, thiab TNF), nrog rau cov tshuaj tiv thaiv kab mob cytokines, hu ua hom I interferons. Interestingly hom I interferons ntawm cov tshuaj tiv thaiv kab mob yog inhibited nyob rau hauv cov hlab ntsha. Kev soj ntsuam ntawm cov ntaub so ntswg extrapulmonary qhia tau hais tias mob hauv lub cevraum, daim siab, thiab lub plawv uas tseem tsis muaj hom I interferon upregulation. Histologically, lub plawv muaj pov thawj ntawm myocarditis thiab microthrombi thaum lubraummuaj tubular o. Cov txiaj ntsig no muab kev nkag siab rau cov kab mob ntau yam kab mob uas tau ntsib los ntawm cov neegCOVID-19thiab tej zaum tus kab mob ntev nyob rau hauv cov neeg nrog post-acute sequelae ntawmSARS-CoV-2(PASC).


cistanche-kidney function-2(56)

Nyem rau Cistanche siv rau lub raum ua haujlwm

Tus kab mob SARS-CoV-2 ua rau muaj qhov mob loj lossis kev tiv thaiv kab mob hauv lub plawv, cov qog ntshav qab zib, thiab tus po, nrog rau cov npe eosinophil hauv cov hnyuv loj.

Cov cim tiv thaiv kab mob ntawm qhov mob, kev tiv thaiv kab mob, thiab cov tshuaj tiv thaiv kab mob kuj tau soj ntsuam hauv cov ntaub so ntswg tsis ua pa nrog rau cov ntaub so ntswg histopathology. Peb tau tshawb xyuas qhov mediastinal lymph node, lub plawv,raum, spleen, siab, thiab txoj hnyuv loj rau kev tswj hwm lub hom phiaj tiv thaiv kab mob categorized li saum toj no los ntawm hom I IFN, hom II / General IFN Teb, thiab Innate / Adaptive Mediators (Fig 6) nrog rau kev tiv thaiv kab mob (Daim duab 7 thiab S4). Yog tias qhov kev ntsuam xyuas thawj zaug ntawm histopathology qhia txog kev koom tes ntawm kev tiv thaiv kab mob tshwj xeeb (S4 Fig), kev tshuaj ntsuam xyuas siab tau ua kom tau txais cov ntaub ntawv tob dua (Daim duab 7). Mediastinal lymph nodes tsis tuaj yeem rov qab los rau hnub 15. Cov ntsiab lus tseem ceeb ntawm cov noob caj noob ces tuaj yeem pom hauv S2 Table. Hom I thiab hom II IFN cov lus teb nyob rau hauv tag nrho cov kab mob extrapulmonary tshwj tsis yog lub siab muaj cov kev cai zoo xws li cov ntsws thiab qhov ntswg turbinates (Fig 6). Cov kev cai ntawm noob caj noob ces yog tus cwj pwm los ntawm qhov txo qis ntawm hom I cov lus teb thiab nce hauv hom II cov lus teb. STAT2 tau txo qis hauv mediastinal lymph node,raum, spleen, thiab txoj hnyuv loj. Lub plawv tau txo qis hauv IRF1 thaum lub plab hnyuv loj tau txo qis hauv IFN-beta (Fig 6). Conversely, cim nce nyob rau hauv IFN-gamma tau pom nyob rau hauv lub mediastinal lymph node thiabraumthiab mus rau qhov qis dua hauv lub siab thiab tus po. CXCL10, T cell chemoattractant, tau nce mus rau qib siab hauv cov poov xab, daim siab, thiab mediastinal lymph node uas cov kev cai yog biphasic hauv cov qog ntshav (Fig 6). Kev tswj hwm ntawm cov noob caj noob ces hauv nruab nrab / hloov pauv hloov pauv hauv tus po thiab cov qog ntshav qab zib tau pom rau txhua lub hom phiaj tiv thaiv kab mob uas tau soj ntsuam nrog kev zam ntawm TGF-beta, IL-5R, thiab CCR3 uas tsis tau tswj hwm zoo. Tshwj xeeb, txoj cai tseem ceeb ntawm CD3, CD4, CD8A, IL-2, IL-21, IL-10, IL-4, IL-5, IL{{13} }}, thiab IL-12 tau sau tseg hauv cov kab mob hauv nruab nrab ntawm cov kab mob no. Txoj cai tswjfwm ntawm innate/adaptive immune mediators tau nthuav tshwj xeeb hauv plawv qhov twg IL-2, IL-10, IL-4, thiab IL-5 tau nce 100 npaug dhau qhov pib . Qhov siab tshaj plaws upregulation ntawm inflammatory cytokines tau kuaj pom nyob rau hauv lub plawv tom qab lub raum, siab, thiab mediastinal lymph node. Hauv plawv, IL-12 tau nce siab thaum ntxov thiab, nrog rau TNF, tseem nce siab nyob rau hnub 15 pi. IL-6 thiab IL-1beta kuj tseem raug cuam tshuam rau hauv lub plawv cov ntaub so ntswg hnub 5 thiab 8 (Daim duab 6). Kev hloov pauv tseem ceeb hauv lub siab tau pom los ntawm kev soj ntsuam histological (S4 Fig). High-resolution imaging pom cov pov thawj ntawm microthrombi (Fig 7A, dawb xub) nrog rau myocarditis (Fig 7B, dawb xub) nyob rau hauv lub plawv. CD14, IL-1beta, thiab TNF tau raug kho thaum ntxov hauv lub raum tab sis txo qis los ntawm hnub 8 txog 12 pi (Daim duab 6) uas tau tshwm sim nrog kev nkag mus ntawm cov kab mob inflammatory mus rau hauv lub raum thiab tej zaum mob raum raug mob lossis raug mob tubular (qhia los ntawm cov xub dawb, Daim duab 7C). IL-6 kev qhia tau txhawb nqa hauv daim siab qhov twg IL-1beta kuj tau nce ntxiv thaum lub sijhawm lig. Mediastinal lymph node muaj biphasic nce hauv IL-12 nrog kev nce ntxiv hauv IL-6 thiab TNF kom quav qib ntawm 12, 8, thiab 11, raws li. Cov hnyuv loj muaj cov kev cai tseem ceeb ntawm IL-5, IL-5R, thiab CCR3 nrog kev nkag mus ntawm eosinophils (Daim duab 7D), tab sis kev tswj tsawg kawg ntawm lwm yam kev sib haum xeeb / hloov kho. Txhawm rau nrog rau kev soj ntsuam ntawm cov kab mob pulmonary ntxiv, peb tau txheeb xyuas cov ntshav chemistry ntawm cov tsiaj nyob rau lub sijhawm kawm los soj ntsuam cov khoom ua haujlwm tsis zoo (S5 Fig). Peb txheeb xyuas cov piam thaj, albumin, alkaline phosphatase, alanine hloov pauv, ntshav urea nitrogen, tag nrho cov bilirubin, thiab tag nrho cov protein raws li lub siab ua haujlwm [27]. Calcium, potassium, albumin, amylase, ntshav urea nitrogen, thiab tag nrho cov protein tau txheeb xyuas los ntsuas lub raum [27]. Kev noj qab haus huv ntawm plab hnyuv tau raug ntsuas los ntawm sodium, potassium, thiab alkaline phosphatase [27]. Kev ua haujlwm plawv tau ntsuas siv sodium, potassium, thiab alanine transferase [27]. Globulin upregulation raug soj ntsuam raws li ib qho kev qhia ntawm antigenic stimulation [27]. Ntawm 14 molecules tshawb fawb, tsuas yog amylase thiab qabzib tau nce siab hauv cov tsiaj txhu uas muaj kab mob thaum piv rau kev tswj hwm, nce siab ntawm 1700 U / L thiab 280 mg / dL, feem, nyob rau hnub 8 pi. Tsis tas li ntawd, cov kev hloov pauv ntawm cov poov tshuaj concentration ([K ntxiv]) yog qhov tseem ceeb tshaj plaws thiab tshwm sim feem ntau cuam tshuam nrog lub sijhawm ntawm txoj kev tshawb fawb vim tias feem coob ntawm cov tib neeg tau nce [K ntxiv] nrog qhov kev hloov loj tshaj plaws pom nyob rau hnub 15. Qhov nce nyob rau hauv albumin kuj tseem ceeb tab sis mob me nyob rau hauv ntau ntawm cov tsiaj. Tag nrho cov protein concentration nce me ntsis hauv feem ntau cov kev kawm, tab sis qhov kev hloov pauv me me thiab yuav tsis muaj qhov tseem ceeb hauv kev kho mob. Lwm cov cim lub siab tau nce siab tom qab hauv chav kawm, suav nrog cov piam thaj (280 mg / dL) hnub 8, alkaline phosphatase (ALP) hnub 12 (3 U / L), thiab ntshav urea nitrogen (BUN) (22 mg / dl) Hnub tim 15. Alanine transferase (ALT), txawm tias nce siab rau hnub 2, tau siab heev rau hnub 12 ntawm qis dua 100 U/L qhia tias muaj peev xwm ua rau daim siab puas. Cov cim rau hauv lub raum kuj nce siab tom qab, hnub 8 rau amylase (1700 U / L), thiab hnub 15 rau cov poov tshuaj thiab BUN (12 thiab 22 mg / dl, feem). BUN nrog ob peb qhov tshwj xeeb muaj peev xwm ua tau raws li lub sijhawm nce ntxiv hauv kev xav. Calcium, nyob rau hauv sib piv, peaked nyob rau hnub 2 ntawm 2.6 mg / dl tab sis poob rau hauv kev siv ntau yam. Cov cim qhia ntawm plab hnyuv thiab mob plawv xws li sodium, pom cov kev cai tsawg kawg nkaus, thaum [K ntxiv] nce qhov sib npaug ntawm lub sijhawm sib kis, nce siab ntawm hnub 15 (12 mg / dl). ALP (mob plab hnyuv) tau siab nyob rau hnub 5 thiab 8 ntawm 3u / L thiab ALT (lub plawv marker) tau nce ntxiv hauv cov kab mob hamsters txheeb ze rau cov hamsters tsis muaj kab mob nyob rau hnub 2, 8, thiab 12 ntawm 75-100 U / L tab sis qhov sib txawv tsis tseem ceeb. Thaum kawg, globulin tau nce siab rau hnub 2 ntawm 0.6 g / dL thiab poob qis dua nyob rau lub sijhawm kawm. Ua ke, kev soj ntsuam ntshav qhia qee qhov kev tsis zoo hauv cov kab mob hauv nruab nrog cev, nrog rau kev txhawb nqa antigenic hauv kev teb rauSARS-CoV-2.


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Fig 6. SARS-Cov-2 kab mob hauv hamsters ua rau muaj kev nce ntxiv hauv cov kab mob thiab lub cev tiv thaiv kab mob cuam tshuam nrog cov noob hauv cov kab mob hauv lub cev tshwj xeeb tuaj yeem qhia txog myocarditis, hloov pauv lub cev tiv thaiv kab mob, thiab eosinophil infiltration rau hauv cov hnyuv loj.qRT-PCR tau ua ntawm RNA muab rho tawm los ntawm cov qog nqaij hlav mediastinal (M) lub plawv, lub raum, tus po, lub siab, thiab cov hnyuv loj los ntawmSARS-CoV-2inculated hamsters. Cov qauv raug soj ntsuam rau hom I interferon cov lus teb ntsig txog (IFN-beta, STAT2, IRF1, IRF3, TLR3), hom II interferon cov lus teb ntsig txog (IFN-gamma, IRF2, STAT1, CXCL10), thiab innate/ Adaptive mediator (CD3, CD4, CD8, CD19, IL-2, TGF-beta, IL-21, IL-10, IL-4, IL-5, IL-5R, IL-13, IL-12, CD14, CCR3, PKR, CCL20, CCL22, IL-1beta, IL-6, TNF) noob leveraging PCR primers tshwj xeeb rau hamster sequences (Table 1). Fold-hloov tau suav los ntawm ΔΔCt tiv thaiv lub hauv paus (Hnub 0) nrog BACT raws li cov noob tu tsev. N yog 3 rau txhua lub sijhawm.

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Kev sib tham

Keeb kwmSARS-CoV-2Kev kis kab mob tau xav tias feem ntau ua rau muaj kab mob ua pa, tab sis tam sim no nws pom tseeb tiasCOVID-19yog ib qho kab mob ntawm ntau lub ntsej muag cuam tshuam rau ntau lub hauv nruab nrog cev [25,26]. Txhawm rau kom nkag siab zoo dua ntawm keeb kwm ntawm tus kab mob thiab ntau yam ntawm cov tsos mob tshwm sim hauv tib neeg, peb tau tshawb xyuas cov kab mob immunopathology thoob plaws hauv lub ntsws thiab cov kab mob tsis ua pa thaum lub sijhawm.SARS-CoV-2kis mob hauv Syrian hamsters. Kab mob nrog 105 TCID50 ntawmSARS-CoV-2ua rau mob me mus rau nruab nrab. Tus kab mob kis tau tsuas yog muaj nyob rau hauv txoj kev ua pa txawm hais tias tus kab mob RNA muaj nyob rau hauv tag nrho cov ntaub so ntswg soj ntsuam. Tus tswv teb cov lus teb profileing hauv cov kab mob ua pa tau txheeb xyuas qhov inhibition ntawm hom I IFN cov lus teb nrog kev nce ntxiv hauv hom II IFNs, inflammatory cytokines, innate thiab adaptive cytokines. Kev soj ntsuam ntawm cov kab mob pulmonary ntxiv kuj pom qhov profile zoo sib xws rau hom I thiab II IFN signaling; Txawm li cas los xij, cov ntaub so ntswg tshwj xeeb tiv thaiv kab mob kuj tau txheeb xyuas. Tshwj xeeb, kev qhia tseem ceeb ntawm innate thiab adaptive mediators tau txheeb xyuas nyob rau hauv lub plawv thiab tus po. Txij li thaum kho antiviral thaum lub sij hawmSARS-CoV-2Kev kis kab mob tsuas yog siv tau thaum lub qhov rais luv [28], hnyav heevCOVID-19yog xav tias yog qhov tshwm sim ntawm lub cev tiv thaiv kab mob dysregulated[29]. Kev nkag siab txog kev tiv thaiv kab mob pathogenesis yog qhov tseem ceeb rau kev txheeb xyuas cov hom phiaj kho mob thiab kho cov tsos mob tsis zoo ua pa cuam tshuam nrogCOVID-19nrog rau lub plawv palpitations los yog migraines thiab ntev-ntev tej yam kev mob nyob rau hauv lub rov qab theem xws li Post Acute Sequelae ntawmSARS-CoV-2kis kab mob (PASC), kuj hu ua long-COVID[30].


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Daim duab 7. Xaiv cov kab mob extrapulmonary muaj cov kab mob sib txawv tom qab SARS-CoV-2 kab mob nrog cov pov thawj ntawm microthrombi thiab myocarditis hauv plawv, tubular ua rau lub raum, thiab eosinophil infiltration hauv txoj hnyuv loj.Lub plawv, lub raum, thiab txoj hnyuv loj tau sau los ntawm txhua tus tsiaj ntawm necropsy thiab tsau hauv 10 feem pua ​​​​ntawm formalin ua ntej paraffin block embedding. Cov ntaub so ntswg raug H&E stained. Lub plawv cov ntaub so ntswg nthuav tawm microthrombi (dawb xub) ntau hnub (A), nrog rau myocarditis hnub 8 (dawb xub) (B). Lub raum raug mob / tubular raug mob (dawb xub) (C). Cov hnyuv loj muaj eosinophil infiltration (dawb xub) (D). Stained cov ntaub so ntswg tau pom thiab ua duab siv Aperio ScanScope XT swb scanner. Cov duab qhia yog sawv cev ntawm 3 tsiaj ib pab pawg, ib lub sij hawm taw tes.


Thawj qhov chaw ntawm kev kis kab mob cuam tshuam rau kev sib kisSARS-CoV-2nyob rau hauv tib neeg yog txoj kev ua pa. Yog li ntawd, thawj qhov tseem ceeb ntawm peb qhov kev tshawb fawb yog cov kab mob ua pa, nrog rau cov tshuaj tiv thaiv kab mob thiab kev tiv thaiv kab mob. Ntawm no peb tau pom cov kab mob ua pa sab saud thiab sab qis thiab cov kab mob cuam tshuam tom qab SARS-CoV-2 tus kab mob hauv Syrian hamsters. Kev kis kab mob hauv lub ntsws ua rau muaj kev mob hnyav uas tshwm sim los ntawm kev nkag mus ntawm cov hlwb inflammatory uas ua rau bronchopneumonia los ntawm hnub 5 pi thiab hemorrhage los ntawm hnub 8. Cov kev tshawb pom no zoo ib yam nrog SARS-CoV-2 kab mob hauv kev tshawb fawb Syrian hamster ua ntej[19, 20,31,32] thiab cov qauv tsiaj loj dua nrog rau rhesus macaques[33] nrog rau mob ntsws loj uas tau txheeb pom hauv qee tus tib neegCOVID-19cov neeg mob[34-36]. Qhov sib xws ntawm cov ntaub ntawv txhawb kev siv cov hamster los ua qauvSARS-CoV-2kab mob tib neeg ua pa kab mob thiab txuam immunopathology. Peb kuj tau sau tseg tias qee cov hamsters tau ntsib kev poob phaus loj dua uas cuam tshuam rau cov kab mob ntau dua. Qhov sib txawv ntawm qhov hnyav tuaj yeem yog vim qhov kev xav ntawm ntuj tsim rau hamsters los nkaum cov zaub mov hauv lawv lub puab tsaig, tsis muaj kev cuam tshuam, lossis muaj cov khoom siv hauv tsev uas tuaj yeem ua rau poob phaus thiab kis kab mob hauv cov tsiaj txhu no. Txij li thaum tag nrho cov tsiaj tau kuaj xyuas cov khoom noj cia hauv lawv lub qhov ncauj thiab txhua tus tsiaj tau txais txiaj ntsig zooSARS-CoV-2tus kab mob no, peb tsis xav tias qhov tshwm sim no yog ib qho kev xav ntawm qhov hnyav ntawm qhov yuam kev lossis kev tsis zoo. Kev ua haujlwm ntxiv yuav tsum tau txiav txim siab seb puas muaj kev sib txawv ntawm caj ces hauv Syrian hamsters los ntawm Charles River. Kev nkag siab txog kev coj dawb huv ntawm cov tsiaj txhu yuav muab cov ntaub ntawv tseem ceeb rau kev siv cov tsiaj no hauv SARS-CoV-2 cov kev tshawb fawb kho mob thiab yog tias nws muaj peev xwm siv qhov kev paub no rau kev txhim kho cov hamster hnyav dua.SARS-CoV-2qauv. Hauv peb txoj kev tshawb fawb, peb kuj tau txheeb xyuas qhov kev txhim kho ntawm cov kab mob tseem ceeb, xws li IL-6 thiab TNF hauv lub ntsws thiab lub qhov ntswg turbinates lees paub cov qauv kev tiv thaiv yav dhau los hauv hamsters [32,37]. Cov kev tshawb pom no yog ib qho tseem ceeb vim tias cov kab mob inflammatory no tau pom tias yog kev kwv yees ntawm cov kab mob hnyav los ntawm kev ntsuam xyuas cov ntshav hauv tib neeg[38-42]. Kev soj ntsuam ntau ntxiv ntawm tus tswv teb cov lus teb rau SARS-CoV-2 nyob rau hauv cov ntaub so ntswg ua pa ntawm hamsters tau ua tiav siv cov ntaub ntawv sau ua ntu zus[43,44]. Hoagland thiab cov npoj yaig tau soj ntsuam lub ntsws ntawmSARS-CoV-2Cov kab mob hamsters rau kev tswj hwm lub cev tiv thaiv kab mob thiab pom muaj kev tswj hwm tseem ceeb ntawm IL-6, TNF, thiab IL-1beta[43] raws li peb cov txiaj ntsig PCR. Hauv lwm txoj kev tshawb fawb ib leeg-cell sequencing tsom xam tau qhia ib qho tseem ceeb T cell teb nrog rau upregulation ntawm IFN-gamma thiab IL-2[44], ob lub cim peb kuj tau sau tseg tias tau hais tawm hauv lub ntsws. Tsis tas li ntawd, peb cov kev soj ntsuam ntawm lub ntsws tau qhia txog kev txhim kho ntawm T cell markers CD3, CD4, thiab CD8A. Qhov tseem ceeb, qhov kev tshuaj ntsuam qRT-PCR peb tau tshaj tawm hauv peb txoj kev tshawb fawb tam sim no tau pom zoo nrog lwm cov kev tshawb fawb no yog li ua pov thawj kev siv qRT-PCR raws li ib txoj hauv kev los ntsuas qhov ua tau zoo ntawm cov tshuaj tiv thaiv thiab kev kho mob tau soj ntsuam hauv hamster SARS-CoV{{ 13}} qauv. Peb cov ntaub ntawv qRT-PCR pro-cov ntaub ntawv muab cov phiaj xwm biomarkers uas tuaj yeem ua haujlwm tau yooj yim. Peb txoj kev tshawb fawb thiab kev txhais lus tsuas yog txwv los ntawm kev muaj cov tshuaj ntsuam xyuas pathogenesis. Cov kev tshawb fawb yav tom ntej yuav tsum siv peb lub vaj huam sib luag ntawm lub hom phiaj tiv thaiv kab mob rau kev siv tshuaj tiv thaiv thiab kev tshawb fawb kho mob.

Cov tshuaj tiv thaiv kab mob yog qhov tseem ceeb rau thawj zaug tswj tus kab mob los ntawm kev puas tsuaj ntawm cov kab mob sib kis thiab kev tiv thaiv kab mob kom txwv tsis pub kis mus rau lwm lub hlwb. Tom qab txheeb xyuas qhov muaj tus kab mob lossis cov kab mob viral antigens, qhov induction ntawm interferons yog lub hauv paus rau kev tsim cov tshuaj tiv thaiv kab mob hauv cov hlwb uas qhov sib npaug ntawm interferons thiab lwm yam innate cytokines yog qhov tseem ceeb rau kev ua haujlwm zoo [45]. Tsis ntev los no, inhibition ntawm hom I interferons (IFN-alpha thiab IFN-beta) tau cuam tshuam nrog cov kab mob hnyav hauvCOVID-19qhia tias tus kab mob no muaj peev xwm los thaiv kev tiv thaiv kab mob tiv thaiv kab mob ua rau muaj kab mob ntau ntxiv [14,46,47].Nyob rau hauv peb txoj kev tshawb fawb, peb pom tias hamsters kis tus kab mob.SARS-CoV-2muaj ib tug prototypical hom II IFN teb. Hauv qhov sib piv, hom IIFN cov lus teb yog downregulated, raws li pov thawj los ntawm kev txo qis hauv IFN-beta noob qhia thiab nce hauv IRF2 gene qhia, hom I antagonist. Ntau qhov kev tshawb fawb tau pom tias muaj kev cuam tshuam hom I IFN cov lus teb tom qab SARS-CoV-2 kab mob hauv vitro[14,{5}}]. IFN dysregulation peb tshaj tawm ntawm no tseem tsis tau txheeb xyuas hauv cov ntaub so ntswg ua pa ntawm tib neeg uas muaj mob hnyav.COVID-19, tab sis kev ntsuam xyuas lub cev tiv thaiv kab mob ntawm cov ntshav tau qhia cov txiaj ntsig zoo sib xws [14,46,47,52]. Txawm hais tias cov txheej txheem inhibiting hom I interferon cov lus teb tsis tau qhia meej, cov kab mob thiab cov tswv tsev tau cuam tshuam rau hauv qhov kev tsis zoo no [53,54].

Dysregulation ntawm cov lus teb interferon yog ib lub tswv yim ua haujlwm los ntawm cov kab mob kom tsis txhob muaj kev tiv thaiv tus tswv tsev. Kev tshawb nrhiav yav dhau los ntawm tus tswv teb teb rau SARS-CoV ( mob hnyav ua pa nyuaj ua pa mob coronavirus 1) thiab MERS-CoV (Middle East respiratory syndrome coronavirus) kab mob qhia tias ntau tus mob coronaviruses siv lub tswv yim no[55-59]. Kev kawm 2020 los ntawm Xia et al. txiav txim siab qhov dysregulation siv los ntawm cov kab mob ua rau mob coronaviruses txuas ntxiv musSARS-CoV-2los ntawm kev ua kom pom tias tag nrho peb ntawm no beta-coronaviruses downregulate hom I interferon txoj kev. Tshwj xeeb tshaj yog, NSP1, NSP6 thiab NSP13 [50] cuam tshuam nrog IFN-beta txhais lus, los ntawm kev thaiv tus tswv ribosome nyob rau hauv rooj plaub ntawm NSP1 [60] los yog tsom cov proteins uas tsim nyog rau IFN-beta induction nyob rau hauv rooj plaub ntawm NSP13 [61]. Lwm yamSARS-CoV-2virus proteins kuj tau cuam tshuam rau hauv interferon downregulation [62]. ORF3b thiab ORF9b ob leeg tshwj xeeb tsom rau mitochondrial antiviral-signaling protein complex txhawm rau txhawm rau tiv thaiv hom I IFN signaling [63,64]. Tus tswv tsev yam cuam tshuamSARS-CoV-2Qhov tshwm sim kis tau muaj xws li hnub nyoog thiab poj niam txiv neej; Tsis tas li ntawd, comorbidities kuj tau cuam tshuam hauv interferon dysre-gulation [65]. Kev kawm 2020 los ntawm Trouillet-Assent thiab al.examinedCOVID-19Cov txiaj ntsig ntawm tus neeg mob hauv ib pawg nrog rau cov tib neeg uas qhia txog hom I IFN thiab cov tib neeg uas muaj qib qis dua ntawm IFN-alpha thiab beta. Lawv pom cov neeg mob uas tsis muaj hom I interferon qhia tau laus dua, thiab feem ntau yuav yog txiv neej piv rau cov uas tau qhia hom I IFNs [66. Nyob rau hauv ib txoj kev tshawb fawb zoo sib xws, cov txheej txheem ntau dua ntawm IFN-alpha2 tau txheeb pom hauv cov poj niam piv rau cov txiv neej|67]. Hauv peb txoj kev tshawb fawb tsis ntev los no, peb pom tias cov neeg laus cov txiv neej ferrets muaj qhov ncua sij hawm-hom I interferon cov lus teb thaum piv rau cov poj niam laus, nrog rau cov txiv neej tsis muaj induction ntawm cov tshuaj tiv thaiv tseem ceeb xws li OASL, MIX1, thiab IDG15 uas ua ke nrog cov kab mob hnyav ntxiv [68] .Nyob rau hauv peb txoj kev tshawb fawb tam sim no siv tus qauv hamster, tag nrho peb cov tsiaj txhu yog txiv neej qhia tias kev tshawb fawb txog kev sib deev yog xav tau kom tau txais kev nkag siab tag nrho ntawm peb hom I interferon dysregulation. Lub sijhawm no, nws tsis paub tias yog vim li cas lossis tus tswv tsev cuam tshuam li cas cuam tshuam cov lus teb rau interferonSARS-CoV-2. Ib txoj kev tshawb fawb los ntawm Bastard thiab al. txheeb xyuas qhov muaj autoantibodies tiv thaiv hom I interferons hauv cov txiv neej uas muaj mob hnyav.COVID-19[69]. Qhov no muaj peev xwm piav qhia txog lub cev tiv thaiv kab mob koom nrog hauv kev txo qis hom I interferon cov lus teb hauv ib pawg ntawm tib neeg cov neeg mob. Cov txheej txheem rau txo cov lus teb interferon hauv peb txoj kev tshawb fawb tam sim no, qhov twg txhua tus hamsters yog cov txiv neej laus, tos kev tshawb nrhiav ntxiv. Ntxiv mus, coj los ua ke, cov kab mob tiv thaiv kab mob peb tau txheeb xyuas ua ke nrog cov kab mob ua pa ua pa qhia tias hamsters yog tus qauv zoo tshaj plaws los tshawb txog cov txheej txheem no thiab kuaj cov tshuaj xws li hom Iinterferons [48,49,70] lossis interferon lambda [Z1, Z2], ob qho tib si tau pom tias muaj txiaj ntsig zoo hauv kev kho mobCOVID-19cov neeg mob [Z3-75] tab sis xav tau kev tshawb fawb ntxiv.


COVID-19:SARS-CoV-2 infection


COVID-19yog ib yam kab mob uas cuam tshuam nrog cov kab mob ntawm cov kab mob ua pa thiab cov kab mob tsis ua pa [25,26, tab sis me ntsis nkag siab txog tus tswv teb cov lus teb sab nraud ntawm txoj hlab pa. Hauv peb txoj kev tshawb fawb, peb tau txheeb xyuas vRNA hauv ntau cov ntaub so ntswg sab nraud ntawm txoj hlab ntsws nrog rau cov qog nqaij hlav mediastinal, lub plawv, lub raum, daim siab, tus po, thiab txoj hnyuv loj. Viral RNA muaj nyob tuaj yeem yog qhov qhia txog tus kab mob muaj sia nyob thiab cov ntaub so ntswg kab mob tab sis kuj tseem tuaj yeem tshwm sim yam tsis muaj tus kab mob nyob. Peb tsis tau pom tus kab mob tseem ceeb nyob sab nraud ntawm txoj hlab ua pa tawm tswv yim tsawg kawg yog tias muaj kev kis kab mob ntxiv rau hauv nruab nrog cev. Txawm li cas los xij, muaj tus kab mob RNA tuaj yeem yog qhov tseem ceeb rau kev kho mob thiab cov txheej txheem cuam tshuam. Lub xub ntiag ntawm tus kab mob RNA tuaj yeem yog qhov tshwm sim ntawm tus kab mob hauv cov ntshav uas tau thauj cov kab mob los yog kab mob antigen uas tau thauj los ntawm cov kab mob antigen mus rau cov ntaub so ntswg tseem ceeb, xws li tus po thiab mediastinal lymph node. Lub xub ntiag ntawm tus kab mob RNA tuaj yeem ua lub luag haujlwm hauv kev tiv thaiv kab mob thiab cuam tshuam cov kab mob hauv cov ntaub so ntswg. Yog li ntawd, peb tau mus tshawb xyuas cov lus teb ntawm lub cev tiv thaiv kab mob hauv cov ntaub so ntswg uas zoo rau tus kab mob RNA. Txawm hais tias peb pom kev txhim kho ntawm inflammatory thiab hom II interferon noob nyob rau hauv tag nrho cov ntaub so ntswg uas tsis yog-pulmonary, cov lus teb zoo tshaj plaws yog qhov nce ntawm kev tiv thaiv-modulatory cytokines hauv lub plawv. Nyob rau hauv lub plawv, peb qhov kev soj ntsuam tau txheeb xyuas qhov nce ntawm cytokines xws li IL-10, IL-2, IL-4, IL-5, IL-5R, IL{ {12}}, CD14, thiab CCR3 qhov twg qee qhov cytokine mRNA cov ntawv sau tau nce ntxiv 100-fold. Txawm hais tias xaiv cytokines ntawm no tuaj yeem tsim los ntawm T cell subsets sib txawv, qhov tsis muaj TGF-beta qhia tias muaj T-txheej txheem hlwb tsawg dua. Tsis tas li ntawd, qhov tsis muaj IL-13 txo qis qhov yuav ua rau TH2 teb. Sib nrug los ntawm T-lymphocytes, qhov nce hauv cov noob qhia ntawm IL-10, TNF, thiab IL{22}} tuaj yeem raug ntaus nqi rau monocytes lossis macrophages[76]. Qhov no tau txhawb ntxiv los ntawm kev nce hauv CD14[76]. Cov lus qhia ntawm IL-5, IL-5R, IL-4, thiab CCR3 kuj qhia txog qhov muaj eosinophils[77]. Ntau qhov kev tshawb fawb soj ntsuam tam sim no tau kuaj pom muaj mob plawv hauvCOVID-19[78-84]. Qhov tseeb, nws tau kwv yees tias kwv yees li 30 feem pua ​​​​ntawm cov neeg tau rov qab losCOVID-19muaj qee yam mob plawv85]. Kev kawm German ntawm 100COVID-19Cov neeg mob pom tias myocardial o yog tshwm sim txawm lub hlis tom qab rov zoo los ntawmSARS-CoV-2kab mob [84]. Nyob rau hauv pawg neeg soj ntsuam, 78 feem pua ​​​​ntawm cov neeg mob tau ntsib cov tsos mob ntsig txog mob plawv tsis hais lawv qib twg.COVID-19qhov hnyav [84]. Monocytes yog cov cell hom paub nkag mus rau hauv lub plawv hauv myocardial o, tsim IL-10, IL-1beta, IL-6, thiab TNF [86], thiab IL-12[87,88], tag nrho cov uas tau hloov kho hauv lub plawv tom qab-SARS-CoV-2inoculation nyob rau hauv peb txoj kev tshawb no. Tsis tas li ntawd, lwm subset ntawm cov teeb meem plawv muaj feem xyuam nrogCOVID-19tau raug ntaus nqi rau eosinophils ua rau eosinophilic myocarditis[89]. Lwm cov kab mob no paub tias ua rau eosinophilic myocarditis tom qab kis kab mob[90-93]. Cov kab mob no feem ntau tshwm sim los ntawm tus kab mob kis rau cov ntaub so ntswg ntawm lub plawv, piv txwv li nrog tus kab mob Coxsackievirus B3 [94]. Eosinophilic myocarditis tau kuaj pom hauvCOVID-19Cov neeg mob, whereupon autopsy lub plawv cov ntaub so ntswg nthuav tawm infiltration ntawm inflammatory hlwb xws li lymphocytes, macrophages, thiab prominently, eosinophils [89]. Hauv qhov no, qhov nce hauv eosinophils thiab tag nrho cov mob hauv lub plawv tau pom txawm tias tsis muaj tus kab mob nyob hauv lub plawv thaum lub sijhawm tuag [95]. Peb pom cov pov thawj hauv peb txoj kev tshawb fawb ntawm eosinophilic myocarditis nyob rau hauv histopathology thiab kuj cytokine kos npe pom nyob rau hauv lub plawv. Nws muaj peev xwm nyob rau hauv peb txoj kev tshawb fawb tias eosinophils ua rau inflammatory mediated cardiomyopathy ntawm upregulation ntawm IL-4, uas tau nce nyob rau hauv cov nqe lus ntawm noob qhia nyob rau hauv lub siab ntawm hamsters hnub 8 tom qab SARS-CoV-2 inoculation. Kev nce ntawm cov poov tshuaj thiab nce me ntsis hauv alanine hloov pauv hauv cov ntshav ntawm cov kab mob hamsters kuj tuaj yeem txhawb kev mob plawv. Nrog rau qhov no hauv siab, cov txheej txheem tswj kev mob plawv ntsig txog COVID-19 tseem tsis tau paub. Xav txog qhov nthuav dav ntawm kev koom tes hauv plawvCOVID-19cov neeg mob, kev tshawb fawb ntxiv yog xav tau kom nkag siab txog cov txheej txheem ntawm tus kab mob. Ntawm no peb tau muab pov thawj tias hamsters yuav pab tau kom nkag siab txog cov txheej txheem ntawm kev raug mob plawv thaum lub sij hawmSARS-CoV-2Kev kuaj mob thiab ntsuas kev kho mob rau cov kab mob no.

Immunologically, peb cov kev soj ntsuam nyob rau hauv tus po thiab mediastinal lymph nodes qhia qhov induction ntawm adaptive kev tiv thaiv. Lub mediastinal lymph node tau txheeb xyuas qhov tseem ceeb ntawm kev tswj hwm biphasic hauv T cell-txog cov noob, nrog kev tswj hwm hauv cov noob qhia ntawm CD3, CD4, IL-2, IL-21, I-10, IL{ {6}}, IL-5, thiab IL-13 nyob rau hnub 2 thiab 15. Qhov profile no qhia txog kev nthuav qhia antigen thaum ntxov hauv cov qog ntshav tawm sai tom qab mob ntsws los ntawm cov hlwb dendritic, uas yuav txhawb nqa los ntawm hnub 2 upregulation ntawm IL-12 ntau lawm hauv cov qog ntshav [96,97]. Dendritic cell migration ua rau T cell activation nws thiaj li culminates hauv IL -2 stimulating T cell loj hlob thiab proliferation [98]. Cov qib Globulin hauv cov ntshav rau hnub 2 tom qab kis kab mob hauv cov kab mob hamsters kuj tseem txhawb kev txhawb nqa antigenic thaum ntxov. Kev tswj hwm ntawm IL-4, IL-5, thiab IL-13 qhia txog TH2 skewed teb[99]. Cov kev tshawb fawb thaum ntxov tau pom tias asymptomatic lossis mob meCOVID-19Cov xwm txheej uas muaj kev tiv thaiv kab mob sib kis mus rau lub cev TH2 tus yam ntxwv los ntawm kev nce hauv IL-4 thiab IL-10[100].IL-10, kev tswj hwm cytokine, kuj tau hloov kho rau hnub 2 hauv peb txoj kev tshawb fawb. Peb cov ntaub ntawv qhia tias activated T hlwb raug recruited mus rau cov ntaub so ntswg nrog ib tug nyob tus kab mob xws li lub qhov ntswg turbinates, qhov uas peb tau pom ib tug nce nyob rau hauv T cell-related noob nyob rau hnub 5 tom qab inoculation. Qhov thib ob upregulation ntawm cov noob hauv cov qog ntshav nyob rau hnub 15 kuj qhia txog kev nthuav dav ntawm T cell subsets. Thaum tsis muaj cov kab mob sib kis nyob rau lub sijhawm no, qhov no tuaj yeem yog qhov nce hauv T cell subsets uas ncaj qha rau kev txhim kho lub cim xeeb teb. Raws li lub hauv paus nco T hlwb kuj tsim IL-2[101] peb cov ntaub ntawv uas qhia tau tias nce IL-2 nyob rau hnub 15 tom qab inoculation tej zaum yuav qhia tau tias T cell nco. IL-21 yog cov kab mob T cell uas muaj feem cuam tshuam tshaj plaws nyob rau hnub 15.IL-21 feem ntau yog tsim los ntawm T-follicular helper cells, ib pawg uas pab cov kab mob hauv nruab nrab B hlwb [102], tshwj xeeb tshaj yog skewing B. cell mus rau affinity maturation thiab nco kev loj hlob. B Cell marker CD19 kuj tau nce ntxiv hauv cov qog ntshav, nrog rau cov kab mob siab tshaj plaws tshwm sim rau hnub 15.A 2021 txoj kev tshawb fawb los ntawm Lakshmanappa li al.assessedSARS-CoV-2Kev kis kab mob hauv rhesus macaques, nthuav tawm cov lus teb T-cell muaj zog hauv cov kab mob hauv nruab nrab ntawm cov qog nqaij hlav hauv nruab nrab nrog kev nce ntxiv hauv CD4, nrog rau T follicular helper cell markers CD28 thiab CXCR5 [103]. Nws yog qhov ua tau qhov nce T cell gene qhia pom nyob rau hauv peb txoj kev tshawb fawb kuj yog qhov qhia txog cov kab mob hauv chaw teb. Ib qho kev ua haujlwm siab T cell teb kuj tau pom nyob rau hauv cov neeg mob nrog SARS-CoV-2 uas rov zoo thiab txhim kho kev nco mus ntev [97,104]. Kev soj ntsuam tob ntxiv nrog cov cim ntxiv ntawm cov tshuaj tiv thaiv kab mob hauv nruab nrab rau kev soj ntsuam cov qog ntshav qab zib yuav zoo rau kev tshawb fawb tshuaj tiv thaiv.


IMPROVE IMMUNITY PREVENT COVID-19


Kev ua kom cov qog ntshav qog ntshav siab kuj tseem tuaj yeem qhia txog pathogenesis. Cov qog nqaij hlav yog tib lub cev tsis ua pa uas muaj tus kab mob nyob. Nyob kis kab mob ntawm cov qog nqaij hlav, nrog rau tus po, tau pom nyob rau hauv tib neeg uas succumbed rauSARS-CoV-2[105].Nyob rau hauv kev tshawb fawb los ntawm Kaneko li al., tib neeg lymph node thiab spleen kuaj los ntawm cov neeg tuagCOVID-19Cov neeg mob tsis muaj BCL6 ntxiv rau B hlwb nrog rau tag nrho cov kab mob hauv nruab nrab. Cov kws sau ntawv xav tias qhov no yog qhov ua rau cov lus teb tsis zoo rauSARS-CoV-2[106]. Txij li thaum peb tau txheeb xyuas qhov tsis zoo ntawm cov tshuaj tiv thaiv kab mob uas tau kuaj pom los ntawm hnub 8 tom qab kis kab mob uas tshwm sim nrog kev txo qis hauv cov kab mob, nws muaj feem ntau tias tus kab mob muaj sia nyob pom hauv cov qog ntshav ntawm peb txoj kev tshawb fawb yog qhia txog kev ua haujlwm B cell teb thiab cov tshuaj tiv thaiv kab mob hauv nruab nrab.

Tus spleen kuj tau pom cov lus teb tseem ceeb ntawm lub cev tiv thaiv kab mob uas tshwm sim los ntawm kev nce hauv cov noob qhia linearly txij hnub 8 txog rau hnub 15. Qhov kev hloov kho lig no cuam tshuam nrog kev koom tes nrog kev tiv thaiv kab mob rau cov kab mob uas yuav tshwm sim tom qab ua rau hauv cov dej ntws hauv zos[107]. Tus spleen, ib lub cev lymphoid, tseem ua rau T thiab B hlwb hauv cov lus teb rau cov kab mob antigen.High gene qhia ntawm CD3, CD4, IL-2, thiab I-21 yog qhia txog T-follicular cell li. zoo li cov kab mob hauv nruab nrab nyob ntawm B cell kev ua haujlwm, raws li peb pom hauv cov qog nqaij hlav [108]. Tsis tas li ntawd, cov lus teb hauv tus po tej zaum yuav yog qhov tshwm sim ntawm viremia, qhov twg plasmacytoid dendritic cells (pDCs) tau koom nrog hauv cov kab mob antigen ntawm TLR7 thiab TLR9 rau CD8 ntxiv rau T cell thiab Natural Killer T (NKT) cell activation. Ob leeg ntawm cov xovtooj ntawm tes no ua haujlwm hauv kev tshem tawm cov kabmob kis kabmob tomqab ua haujlwm hauv tus po los ntawm IFN-beta thiab IL-12 [109], uas tau nce hauv peb tus qauv, nrog rau CD8.IL-12 , IL-10, thiab CD14 tau kho nyob rau hauv tus po ntawm tus kab mob hamsters, muaj peev xwm taw tes rau macrophage phagocytic kev ua si[110,111]. Tsis tas li ntawd, innate lymphoid cells (ILCs) nyob rau hauv cov poov xab txhawb cov ntaub so ntswg kho nyob rau hauv teb rau raug mob thiab tsim IL-5 thiab IL{22}}[112]. Ua ke, cov lus teb tom qab no nyob rau hauv tus po cov ntsiab lus rau kev rov ua haujlwm ntawm tus po, nrog rau kev muaj peev xwm lymphocyte activation rau cov lus teb ntev ntev.

Cov hnyuv loj tau pom cov kev cai tsawg kawg ntawm cov tshuaj ntsuam xyuas cytokines, nrog rau qhov tshwj xeeb ntawm I-5, IL-5R, thiab CCR3. Kev nthuav qhia ntawm tag nrho peb ntawm cov noob no tau nce ntau heev nyob rau hnub 2 txog 15 nrog lub ncov fold-hloov ntawm 74 rau IL-5, piv rau lub hauv paus rau hnub 8. IL-5 feem ntau yog secreted los ntawm hom 2 T. -helper cells thiab eosinophils[113]. Muab cov qib qis ntawm cov noob qhia ntawm lwm cov noob ntsig txog Th2, xws li IL-4 thiab IL-13, thiab qhov nce hauv cov cim eosinophil paub IL-5R thiab CCR3, nws zoo li IL{ {18}} feem ntau yog tsim los ntawm eosinophils uas tuaj yeem pom hauv peb qhov kev soj ntsuam histological ntawm txoj hnyuv loj. Eosinophils ua lub luag haujlwm ncaj qha hauv kev tiv thaiv kab mob, raws li pov thawj los ntawm RNases hauv lawv cov granules thiab tau cuam tshuam nrog kev tshem tawm ntawm lwm cov kab mob ua pa [114,115]. Ntau cov eosinophils kuj pom nyob rau hauv lub plab zom mov [116].Hauv peb txoj kev tshawb fawb, cov hnyuv loj ntawm cov kab mob hamsters tsis pom cov kab mob nyob. Cov hnyuv loj yog, txawm li cas los xij, zoo rauSARS-CoV-2viral RNA nyob rau hnub 2 thiab 5post inoculation, ib qho kev tshawb pom zoo ib yam nrog Sia li al., uas kuj tau soj ntsuam vRNA nyob rau hauv txoj hnyuv thaum tsis muaj ib qho inflammatory teb [20]. Txog li 20 feem puaCOVID-19Cov neeg mob qhia txog cov tsos mob ntawm plab hnyuv xws li raws plab [39,117] nrog cov kab mob raug tso rau hauv cov quav[118]. Qhov no tuaj yeem piav qhia los ntawm qhov txo qis hauv eosinophils uas tau tshaj tawm thaum muaj mob hnyavCOVID-19[119-121]. Qhov nce hauv IL-5 gene qhia los ntawm eosinophils tuaj yeem ua rau muaj kev tiv thaiv kab mob hauv cov hnyuv loj, yog li tiv thaiv kab mob. Kev tshawb nrhiav ntxiv yog xav tau kom paub meej tias hom cell tiag tiag uas ua rau qhov kev nce qib IL -5 teb.

Hauv peb txoj kev tshawb fawb peb kuj tshawb xyuas cov ntshav chemistry ntawmSARS-CoV-2kis Syrian hamsters. Peb tau txiav txim siab siv ntau yam siv cov hamsters uas tsis muaj kab mob los ntawm peb cov tsiaj txhu thiab muab piv rau cov ntawv nyeem rau cov ntaub ntawv luam tawm rau hamsters, tshwj xeeb yog Syrian hamsters [122]. Qee qhov ua ntej ua ntej uas yuav cuam tshuam rau cov ntshav chemistry ntawm peb cov tsiaj ua ntej kev kis tus kab mob uas yuav tsum tau txiav txim siab rau kev tsom xam suav nrog qib kev ntxhov siab uas cov tsiaj yuav raug mob ntxiv nrog rau cov tshuaj loog isoflurane siv thaum cov ntshav tau kos uas tuaj yeem hloov pauv cov ntshav chemistry. Nws tau raug pom tias cov piam thaj, ALT, ALP, thiab inorganic phosphorus ntau dua hauv cov nas hauv qab isoflurane thiab lwm yam tshuaj loog tsis tau qhia ntawm no[123].Hauv peb txoj kev tshawb fawb ntawm SARS-CoV-2 tus kab mob hamsters, ib qho ntawm Cov kev hloov pauv tseem ceeb tshaj plaws tom qab kis kab mob suav nrog cov poov tshuaj ntau ntxiv uas tau nce ntxiv raws sijhawm. Potassium, uas yog lub hauv paus, ua raws li qhov tsis tuaj yeem pauv rau Hydrogen (H') (acid) thaum tus neeg mob nyob hauv lub xeev acidic. Txij li cov ntshav acidosis tuaj yeem tshwm sim los ntawm kev hloov pauv hauv kev ua pa ntawm lub ntsws nws tsis yog qhov xav tsis thoob tias cov hamsters uas pom cov tsos mob ntawm kev mob ntsws / ua pa nyuaj (qhia tias muaj cov pa roj carbon dioxide (CO2) nce ntxiv) khaws cia (lossis tshem tawm tsawg dua) thiab qis Oxygen ( O2) tau noj vim qhov txo qis ntawm alveolar muaj nuj nqi) yuav nkag mus rau hauv lub xeev acid ua rau cov poov tshuaj nce hauv cov ntshav. Hais txog qib qis albumin hauv kev sib piv rau peb cov kev siv ntau yam, nws yuav tsum tau xav tias albumin yuav nce ntxiv rau cov lus teb rau cov kab mob cytokine. Nws muaj peev xwm hais tias cov qib qis ntawm albumin yog vim kev siv isoflurane uas tau pom yav dhau los [122-124]. Hauv kev hwm rau cov piam thaj hauv lub sijhawm, feem ntau ntawm cov tsiaj muaj kab mob muaj qhov nce hauv cov piam thaj hauv cov lus qhia cortisol-induced stress, epinephrine-induced excitement, los yog dysregulation hauv insulin ntau lawm los yog secretion / receptor cuam tshuam. Hauv cov ntsiab lus, qhov kev tshawb pom nthuav dav tshaj plaws ntawm qhov kev tshuaj ntsuam no yog cov lus qhia txog kev txo qis cov pa oxygen cuam tshuam nrog kev nce qib poov tshuaj. Cov txiaj ntsig no qhia tias kev saib xyuas cov poov tshuaj tuaj yeem siv los txheeb xyuas kev mob ntsws thaum lub sijhawm nyob hauv lub neejCOVID-19tsiaj kawm. Tsiv mus tom ntej, txoj haujlwm no tseem tuaj yeem siv los tsim cov txiaj ntsig siv rau Syrian hamster SARS-CoV-2 tus qauv kab mob thiab siv rau kev kuaj mob hauv lub neej.

Peb txoj kev tshawb fawb muab cov kev nkag siab tseem ceeb rau hauvSARS-CoV-2kab mob thiabCOVID-19kab mob kev cai. Preclinical qauv yog lub hauv paus ntawm kev tshawb fawb biomedical muab lub peev xwm los sim cais cov kab mob thiab tseem ntsuas cov kev kho mob muaj peev xwm suav nrog cov tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, thiab tshuaj tiv thaiv. Raws liSARS-CoV-2thawj zaug tau tshwm sim, peb muaj kev nkag siab tsis txaus ntawm cov txheej txheem ntawm pathogenesis, tsis muaj kev kho mob lossis kev tiv thaiv kab mob, thiab tsis muaj cov qauv ua ntej los ua kom muaj txiaj ntsig rau kev tshawb nrhiav kev kho mob. Txij li thaum lub sij hawm ntawm tus kab mob tshwm sim, loj leaps tau ua tshwj xeeb tshaj yog nyob rau hauv preclinical qauv kev loj hlob, tab sis peb to taub txog.COVID-19thiab nws ntau manifestations tseem txwv. Peb txoj kev tshawb fawb tau lees paub tus kab mob tropism thiab ua pa pathology yav dhau los pom hauv pebSARS-COV-2hamster kev tshawb fawb tab sis kuj tseem tuaj yeem txuas ntxiv peb txoj kev nkag siab txog kev tiv thaiv kab mob thiab kab mob hauv lub ntsws thiab dhau mus.


SARS-CoV-2 infection and COVID-19 disease: IMPROVE IMMUNITY

Cov ntaub ntawv

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Nco tseg:cov saum toj no tsis yog ib daim ntawv teev tag nrho


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