Tus Kab Mob Khaus Viv-Kidney Controversy: SARS-CoV-2 Puas Yog Tus Kab Mob Raum Direct?
Mar 22, 2022
Wei Ling LauaJonathan E. ZuckermanbAjay GuptaaKamyar Kalantar-Zadeha
Abstract
Cov ntsiab lus:Kev txiav txim siab seb SARS-CoV-2 ua rau tus kab mob kis ncaj qhalub raumyog qhov nyuaj vim muaj kev txwv hauv cov duab thiab cov cuab yeej molecular.
Lub ntsiab lus ntawm Kev Tshawb Fawb:Muaj coob tus tsis sib haum xeebraumbiopsy thiab autopsy cov ntaub ntawv qhia txog qhov teeb meem tsis sib haum xeeb no.
Kev xav thib ob:Raws li cov pov thawj sib sau ua ke, cov kev kho mob uas txhim kho hemodynamic stability thiab oxygenation, los yog dampen complement activation, zoo li yuav ameliorate mob.raum raug mobhauv COVID-19. Lub sijhawm no, txawm tias inhibition ntawm tus kab mob kis thiab rov ua dua ncaj qha modulatesraumkev puas tsuaj yog inconclusive.
Ntsiab lus:COVID-19 · SARS-CoV-2 ·Lub raumpathology · Immunohistochemistry · Ribonucleic acid
Hu rau:joanna.jia@wecistanche.com
Cistanchedeserticolativ thaivraumkab mob, nyem qhov no kom tau txais cov qauv
Taw qhia
Tus mob hnyav ua pa nyuaj rau tus mob coronavirus 2 (SARS-CoV-2) tus kab mob tshwm sim hauv Suav teb thaum kawg ntawm xyoo 2019 tau ua rau COVID-19 kis thoob qhov txhia chaw, uas tau thov ntau dua 1 lab lub neej txij li lub Kaum Hlis 1, 2020. SARS-CoV-2 qhia dav dav organotropism, uas yog, cov hlwb hauv ntau lub cev tuaj yeem kis tau ncaj qha thiab tuaj yeem ua lub chaw cia rau tus kab mob. Angiotensin-converting enzyme 2 (ACE2) yog lub luag haujlwm receptor ntawm SARS-CoV-2 thiab tau nthuav tawm nyob rau hauv feem ntau hauv nruab nrog cev, nrog rau kev qhia siab tshaj plaws hauvlub raum(proximal tubular cells thiab podocytes) thiab ileum [1]. Muab qhov paub txog ACE2 cov ntaub so ntswg faib, kev sib koom ua ke ntawm mob hnyavraumKev raug mob thiab muaj kev pheej hmoo tuag ntau ntxiv hauv COVID-19, thiab qhov xav tau ceev los txheeb xyuas cov hom phiaj kho mob, nws tsis xav tsis thoob tias SARS-CoV- 2- koom nrograumkev raug mob yog thaj tsam ntawm kev tshawb fawb nquag.
Muaj ntau txoj hauv kev tsis ncaj ntawm SARS-CoV-2 acuteraumraug mobtau elucidated.Lub raumpathology qhia tau hais tias muaj ntau yam kev raug mob ntawm tubular raug mob uas suav nrog necrosis thaum mob hnyav, vim muaj kev sib xyaw ntawm cov kab mob cytokine cua daj cua dub, hypoxemia, thiab polypharmacy. Ntxiv thiab coagulation cascades tau tshwm sim thiab tuaj yeem qhib ib leeg [2]; Txawm li cas los xij, lub raum thrombotic microangiopathy tsuas muaj nyob rau hauv ib pawg ntawm cov xwm txheej [3-6]. Qee qhov xwm txheej ntawm tus kab mob glomerular tau tshaj tawm, nrog rau feem ntau yog collapsing glomerulopathy [6-10] uas tuaj yeem cuam tshuam nrog kev pheej hmoo siab APOL1 gene variants [7-9]. Cov kab mob hloov me me, membranous glomerupathies, kab mob los tiv thaiv GBM, kab mob cuam tshuam nrog glomerulonephritis, thiab ANCA-associated vasculitis kuj tau tshaj tawm ib txhij nrog SARS-CoV-2 kab mob [3, 6, 7, 11–13].
Seb direct viralraumKev kis mob tshwm sim nrog SARS-CoV-2 yog lub ntsiab lus tsis sib haum xeeb. Cov kev kuaj pom muaj xws li histology, uas yog, immunohistochemistry (IHC) thiab kis tau tus mob electron microscopy (TEM), thiab ribonucleic acid (RNA) assays, uas yog, nyob rau hauv situ hybridization (RNA-ISH) thiab quantitative real-time reverse transcriptase-polymerase chain reaction. (RT-PCR). Cov txheej txheem no muaj qhov txwv tsis pub muaj.
IHC tsuas siv tau yog tias qhov tshuaj tiv thaiv kab mob tshwj xeeb; Hmoov tsis zoo, cov tshuaj tiv thaiv muaj nyob rau hauv kev lag luam tsom rau SARS-CoV-2 nucleocapsid protein (NP) thiab spike (S) antigens tsis tau raug lees paub zoo. Tshwj xeeb, muaj kev txhawj xeeb nrog cov tshuaj tiv thaiv SARS-NP los tiv thaiv lub cev los ntawm clone ID: 019 (Sino Biological, Beijing, Tuam Tshoj) uas tau sim nyob rau hauv ntau yam mob thiab tau pom tias tsis muaj qhov zoo staining hauvraumparenchyma [8]. Tsis tas li ntawd, cov tubules ze ze yog qhov ua rau tsis muaj qhov tshwj xeeb ntawm ntau cov tshuaj tiv thaiv kab mob vim lawv qhov muaj peev xwm nqus tau.
TEM yog qhov nyuaj raws li ntau cov txheej txheem ultrastructures (lub npe hu ua cov kab mob zoo li cov kab mob) tuaj yeem ua rau cov kab mob sib txawv [14]. Piv txwv li, multivesicular lub cev nyob rau hauv podocyte cytoplasm thiab clathrin-coated endocytosed vesicles nyob rau hauv tubular epithelial hlwb tuaj yeem muaj cov tsos mob ntawm tus kab mob corona [8, 15]. Ntau qhov kev tshawb nrhiav ntawm kev kuaj mob ua ntej-COVID era tau pom cov qauv morphological zoo ib yam rau cov uas tau tshaj tawm tias "SARS-CoV-2 cov kab mob kis" [16, 17]. Txog niaj hnub no, tsis muaj kev tshawb fawb siv immunoelectron microscopy rau cov kab mob tshwj xeeb antigens tau tshaj tawm.
RNA kev ntsuam xyuas raug suav hais tias yog qhov tseem ceeb tshaj plaws thiab tshwj xeeb tab sis yuav raug txwv yog tias tus kab mob no muaj qis dua qib ntawm kev tshawb pom. RT-PCR xav tau homogenization ntawm cov qauv ntaub so ntswg thiab tuaj yeem tshaj tawm qhov tsis zoo yog tias cov ntshav tsis ua tib zoo ntxuav tawm ntawm cov qauv, xws li qhov kev sim no tau kuaj pom tus kab mob extracellular circulating virus. Tsis tas li ntawd, yog tias cov ntaub so ntswg tau txais thaum lub sij hawm ntawm kev txiav txim siab, qhov twg ntawm postmortem autolysis thiab cell degeneration tuaj yeem cuam tshuam qhov kev txhais ntawm kev kuaj kab mob.
cistanches herba rau lub raum
Cov kev tshawb fawb tsis sib haum xeeb tshaj tawm thaum lub Plaub Hlis thiab Kaum Ib Hlis 2020 tau ua rau muaj kev sib cav tsis tu ncua txog seb SARS-CoV-2 ua rau ncaj qharaumkab mob (Table 1). Ntau qhov kev tshawb fawb tom qab tuag tau tshaj tawm kev kuaj pom ntawm SARS-CoV-2los ntawm electron microscopy, IHC, thiab/lossis RNA assays [18–23] (xws li ib qho medRxiv preprint los ntawm Diao li al.). Ntawm qhov kev ceeb toom, 2 ntawm cov kev tshawb fawb no tau siv cov tshuaj tiv thaiv-SARS-NP cov tshuaj tiv thaiv uas tau ua rau muaj kev txhawj xeeb rau cov teeb liab tsis tshwj xeeb raws li tau tham saum toj no [8]. Puelles et al. [22] muab pov thawj txaus ntshai ntawm punctate staining ntawm tus kab mob RNA hauv glomeruli thiab tubules los ntawm hauv situ hybridization, thiab lawv txoj kev tshawb fawb suav nrog ntau yam SARS-CoV-2 kev tswj tsis zoo. Txoj kev tshawb no los ntawm Braun et al. [20] pom tau tias muaj kev vam meej kev kis kab mob ntawm cov kab mob primate raum tubular epithelial hlwb, siv homogenized raum cov qauv uas tau txais thaum lub sij hawm autopsy los ntawm SARS-CoV-2 cov neeg mob; Txawm li cas los xij, qhov ua tau ntawm tus kab mob muaj nyob hauv cov ntshav seem hauv lub raum cov ntaub so ntswg tuaj yeem piav qhia qhov kev soj ntsuam no.
Ntawm qhov kev ceeb toom, nyuaj txhais RNA-ISH hauv cov ntaub so ntswg tuag tau raug tshaj tawm [5] qhov uas tsis tshua muaj tubular zoo nyob rau hauv ob qho tib si SARS-CoV-2-cov neeg mob zoo thiab tsis zoo. Yog li, hauv cov ntaub so ntswg autopsy, RNA-ISH tuaj yeem pom qhov tsis zoo, thiab qhov pib, nrog rau cov yam ntxwv ntawm qhov tseeb qhov zoo, tseem yuav tsim.
Hauv qhov sib piv, cov ntaub ntawv biopsy los ntawm cov neeg mob nyob thiab lwm yam kev tshawb fawb txog kev tuag tsis tau kuaj pom SARS-CoV-2 hauv lub raum ntawm IHC, RT-PCR, thiab RNA-ISH [3, 5–11, 15, 24, 25] . Nws muaj peev xwm hais tias qhov tsis muaj kev kuaj pom tus kab mob tuaj yeem cuam tshuam txog kev tshem tawm cov kab mob hauv lub raum vim tias muaj kev ncua ntau zaus ntawm tus kab mob SARS-CoV-2 thawj zaug thiab lub raum biopsy lossis autopsy. Txawm li cas los xij, cov lus ceeb toom tsis zoo yog qhov zoo sib xws nrog qhov tseeb tias SARS-CoV-2 tsis tshua pom nyob rau hauv cov zis, thiab cov zis tsis cuam tshuam nrog rau qib ntawm lub raum raug mob [26, 27]. Tsis tas li ntawd, cov ntshav kuj feem ntau qis lossis tsis tuaj yeem kuaj pom [27]. Cov ntaub ntawv no txhawb qhov kev xav tias feem ntau ntawm SARS- CoV-2 lub raum teeb meem yuav tshwm sim los ntawm cov txheej txheem tsis ncaj, txawm tias qee tus neeg mob yuav tshwm sim ncaj qha raum kab mob.
Muab qhov kev tsis sib haum xeeb no, kev tshawb fawb yav tom ntej yuav tsum siv cov kev tswj xyuas nruj nrog rau ob qho tib si SARS-CoV-2- cov ntaub so ntswg zoo thiab tsis zoo. Multimodel nrhiav tswv yim xws li IHC, RNA-ISH, thiab immunoelectron microscopy yog lav. Peb ntseeg tias tsis muaj kev kuaj pom ntawm immunoelectron, kev ntsuas morphologic los ntawm electron microscopy ib leeg tsis txaus kom paub meej tias muaj cov kab mob kis. Hmoov zoo, luam tawm cov kev tshawb fawb txog kev siv tau ntawm SARS-CoV-2 cov tshuaj tiv thaiv thiab RNA-ISH tau tshwm sim [28] uas yuav pab qhia kev siv cov tshuaj tiv thaiv uas tsim nyog rau kev lag luam thiab RNA-ISH probes.
Cov ntaub ntawv pov thawj ntawm cov kab mob sib kis hauv tib neeg lub raum hlwb tseem yuav raug lees paub [29, 30]. Raws li cov pov thawj sib sau ua ke, cov kev kho mob uas txhim kho hemodynamic stability thiab oxygenation, los yog dampen complement activation, yuav ua rau kom mob raum mob raum hauv COVID-19. Lub sijhawm no, txawm tias inhibition ntawm tus kab mob kis thiab rov ua dua ncaj qha hloov kho lub raum puas yog qhov tsis tiav.
cistanche erectile kawg rau lub raum
Daim ntawv qhia tsis sib haum xeeb
WL Lau tau txais kev qhuas thiab / lossis kev txhawb nqa los ntawm Fresenius, Hub Therapeutics, Roche, Sanofi, thiab ZS Pharma. JE Zuckerman yog tus kws pab tswv yim them nyiaj rau Leica Biosystems. A. Gupta tau foob 3 daim ntawv thov patent rau kev siv PGD2 thiab thromboxane A2 antagonists, suav nrog ramatroban, raws li kev kho mob rau CO- VID-19 (Daim Ntawv Thov No. ua ntaub ntawv rau lub Plaub Hlis 3, 2020; thiab 63/027,751 ua rau lub Tsib Hlis 2, 2020). K. Kalantar-Zadeh tau txais kev qhuas thiab / lossis kev txhawb nqa los ntawm Abbott, Abbvie, ACI Clinical (Cara Therapeutics), Akebia, Alexion, Amgen, Ardelyx, Astra-Zeneca, Aveo, BBraun, Chugai, Cytokinetics, Daiichi, DaVita, Fresenius, Genentech, Haymarket Media, Hospira, Kabi, Keryx, Kissei, Novartis, Pfizer, Regulus, Relypsa, Resverlogix, Sandoz, Sanofi, Shire, Vifor, UpToDate, thiab ZS Pharma.
ib qho kev faib ntawm Nephrology, Hypertension thiab raum Transplantation, University of California Irvine School of Medicine, Orange, CA, USA;
b Department of Pathology and Laboratory Medicine, David Geffen Lub Tsev Kawm Ntawv ntawm Tshuaj ntawm University of California Los Angeles, Los Angeles, CA, USA
Cov peev txheej
Cov kws sau ntawv lees paub txog nyiaj txiag los ntawm NIH NINDS R01- NS113337 (WLL) thiab NIH NIDDK K24-DK091419 (KKZ).
Sau Kev Pab Txhawb
WLL thiab JEZ tau sau cov ntawv sau. WLL, JEZ, AG, thiab KKZ tau hloov kho thiab pom zoo cov ntawv sau kawg.
cistanche thiab tongkat ali rau lub raum
Cov ntaub ntawv
1. Martinez-Rojas MA, Vega-Vega O, Bobadilla NA. Lub raum puas yog lub hom phiaj ntawm SARS-CoV-2? Am J Physiol Raum Physiol. 2020 Lub Rau Hli 1; 318 (6): F1454–f62.
2. Batlle D, Soler MJ, Sparks MA, Hiremath S, South AM, Welling PA, et al. Mob raum raug mob hauv COVID-19: cov pov thawj tshwm sim ntawm cov kab mob sib txawv. J Am Soc Nephrol. Peb Hlis 2020, 31(7): 1380-3.
3. Akilesh S, Nast CC, Yamashita M, Henriksen K, Charu V, Troxell ML, et al. Multicenter clinicopathologic correlation ntawm lub raum biopsies ua nyob rau hauv COVID-19 cov neeg mob uas muaj mob raum mob los yog proteinuria. Am J Raum Dis. 2021 Lub Ib Hlis; 77(1): 82–93.e1.
4. Jhaveri KD, Meir LR, Flores Chang BS, Parikh R, Wanchoo R, Barilla-LaBarca ML, et al. Thrombotic microangiopathy hauv tus neeg mob nrog COVID-19. Raum Int. 2020 Aug; 98(2): 509–12.
5. Santoriello D, Khairallah P, Bomback AS, Xu K, Kudose S, Batal I, et al. Postmortem raum pathology tshawb pom hauv cov neeg mob nrog COVID-19. J Am Soc Nephrol. 2020; 31(9): 2158–67.
6. Sharma P, Uppal NN, Wanchoo R, Shah HH, Yang Y, Parikh R, et al. COVID-19: cuam tshuam rau lub raum raug mob: ib rooj plaub ntawm kev tshawb pom lub raum. J Am Soc Nephrol. 2020; 31(9): 1948–58.
7. Kudose S, Batal I, Santoriello D, Xu K, Barasch J, Peleg Y, et al. Kev tshawb pom ntawm lub raum biopsy hauv cov neeg mob nrog COVID-19. J Am Soc Nephrol. 2020; 31(9): 1959–68.
8. Larsen CP, Bourne TD, Wilson JD, Saqqa O, Sharshir MA. Kev sib tsoo glomerulopathies hauv tus neeg mob nrog COVID-19. Raum Int Rep. 2020 Jun; 5(6:935–9.
9. Nasr SH, Alexander MP, Cornell LD, Herrera LH, Fidler ME, Said SM, et al. Kev tshawb pom ntawm lub raum biopsy hauv cov neeg mob uas muaj COVID-19, mob raum, thiab proteinuria. Am J Raum Dis.
18 nov 2020.
10. Peleg Y, Kudos S, D'Agati V, Siddall E, Ahmad S, Nickolas T, et al. Mob raum raug mob vim yog tawg glomerupathies tom qab tus kab mob COVID-19. Raum Int Rep. 2020 Lub Plaub Hlis 28; 5(6): 940–5.
11. Akilesh S, Nast CC, Yamashita M, Henriksen K, Charu V, Troxell ML, et al. Multicenter clinicopathologic correlation ntawm lub raum biopsies ua nyob rau hauv COVID-19 cov neeg mob uas muaj mob raum mob los yog proteinuria. Am J Raum Dis. 2021 Lub Ib Hlis; 77(1): 82–93.e1.
12. Prendecki M, Clarke C, Cairns T, Cook T, Roufosse C, Thomas D, et al. Anti-glomerular hauv qab daim nyias nyias kab mob thaum lub sij hawm CO- VID-19 muaj thoob qhov txhia chaw. Raum Int. Sep 2020; 98(3):780–1 : kuv.
13. Uppal NN, Kello N, Shah HH, Khanin Y, De Oleo IR, Epstein E, et al. De Novo ANCA-as-sociated vasculitis nrog glomerulonephritis hauv COVID-19. Raum Int Rep. 2020 Nov; 5(11): 2079–83.
14. Calomeni E, Satoskar A, Ayoub I, Brodsky S, Rovin BH, Nadasdy T. Multivesicular body mimicking SARS-CoV-2 in patient without COVID-19.Kidney Int. 2020 Lub Xya hli ntuj; 98(1): 233–4.
15. Golmai P, Larsen CP, DeVita MV, Wahl SJ, Weins A, Rennke HG, et al. Histopathologic thiab ultrastructural tshawb pom nyob rau hauv postmortem raum biopsy cov ntaub ntawv nyob rau hauv 12 cov neeg mob nrog AKI thiab COVID-19.J Am Soc Nephrol. 2020; 31(9): 1944–7.
