347 Ibigize imiti idafite ibyuma Ubunini bwamaraso yimitsi cyangwa capillary, yihariye SARS-CoV-2, ibisubizo bya T-selile bigena ubudahangarwa kuri COVID-19.

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347 ibyuma bitarimo ibyuma

Ibyuma bitagira umwanda 347 Coil Tube Ibigize imiti

Ibigize imiti hamwe nubukanishi bwibyuma bitagira umwanda 347 coil coil nibi bikurikira:
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Utugingo ngengabuzima twa SARS-CoV-2 twibwira ko turinda kwandura no gutera imbere kwa COVID-19, ariko nta bimenyetso bifatika bibigaragaza.Hano, twagereranije ibipimo byose byamaraso ya SARS-CoV-2 yihariye ya interferon-γ nziza ya T hamwe nibisubizo byiza byo gupima COVID-19 (PCR na / cyangwa gutembera kuruhande) mumezi 6 uhereye igihe Lian yakusanyije.Mu bitabiriye 148 batanze urugero rw’amaraso y’imitsi, ubunini bw’imikorere ya selile ya SARS-CoV-2 yari hejuru cyane ku bakomeje kurindwa kurusha abanduye (P <0.0001).% ibyago byo kwandura, mugihe ubukana bwinshi bwagabanije iyi ngaruka kugera kuri 5.4%.Ibi bisubizo byahurijwe hamwe ku bandi 299 bitabiriye amahugurwa bapimishije amaraso manini ya capillary yorohereza abantu kubona amakuru y’ubudahangarwa bwa T-selile (14.9% na 4.4%).Rero, gupima ingirabuzimafatizo T yihariye ya SARS-CoV-2 irashobora guhanura ibyago byo kwandura kandi bigomba gusuzumwa mugihe hagenzurwa ubudahangarwa bw’umuntu ku giti cye n’abaturage.
Gupima no gusobanukirwa n’ubudahangarwa bw'umubiri wanduye SARS-CoV-2 ni ngombwa gushyiraho ingamba zifatika zo mu gihe kizaza hagamijwe kugabanya ingaruka z’ubuzima rusange n’ubukungu by’indwara ziterwa na COVID-19.Kumenya isano iri hagati y’ubudahangarwa bizatanga amakuru y’ingenzi ku bijyanye n’uko abaturage bashobora kwandura virusi, bikaba bishoboka ko baburira hakiri kare ko bajyanwa mu bitaro, kandi bikanemerera abantu kwikemurira ibibazo byabo byo kwandura ndetse n’ibyago byo kwanduza abandi.Igenzura ry’ubudahangarwa ryagaragaye ko ari ingenzi gusuzuma imikorere y’inkingo za COVID-19 ku barwayi bafite ubuzima bwiza kandi bafite ibyago byinshi 1,2,3 cyane cyane muri SARS-CoV-24, kandi gutahura ubudahangarwa bizasobanura ko ari ngombwa kongera ubudahangarwa Kurinda inkingo no kwirinda icyorezo kizaza.
Urwego rwumuntu kudahangarwa kwandura SARS-CoV-2 biterwa nimpamvu nyinshi: umutwaro wa virusi mugihe cyo guhura, virusi, imyaka, urukingo rwanduye / kwandura, indwara, imiti, cyane cyane, kwandura SARS-CoV .2 ubudahangarwa bw'umubiri bwo kurwanya indwara bubaho mugihe cyo kwandura virusi5.Isuzuma ry’ubudahangarwa bw'umubiri wanduye SARS-CoV-2 na / cyangwa inkingo byibanze ku bushakashatsi bwakozwe na serologiya bupima ko antibodiyite zihariye za poroteyine zubaka (urugero: spike glycoprotein).Ariko, kuba antibodies zihari cyangwa zidahari ntizigaragaza neza igisubizo cyikingira cyikingira, kuko ibisubizo byatanzwe mugihe cyigihe6 no kutabogama kwa SARS-CoV-2 muburyo bwo gukira cyangwa gukingirwa inshuro ebyiri Ibikorwa bidakomeye, bishobora gutera abantu benshi umubare wanduye.Mubyukuri, kurinda ibimenyetso COVID-19 byatewe na Omicron variant (B.1.1.529) byagabanutse kugera kuri 10% nyuma y amezi 4-6 gusa yo gukingirwa kwa mRNA, nubwo kurinda indwara zikomeye byakomeje> 68% byibuze amezi 7.Gupima imiterere yibikoresho bya T T ibisubizo, bitanga uburinzi bwigihe kirekire kwirinda kwandura virusi, nicyo kimenyetso cyiza cyerekana kwandura SARS-CoV-2, bityo rero bikaba byerekana neza ibyago byo kwipimisha neza kuri COVID-199, kuva T yihariye selile zirashobora kwirinda kwandura.nta serokonversion10,11.Icyakora, gupima ibisubizo by'uturemangingo T ntitwitabiriwe cyane kubera ingorane zishingiye ku buryo n'ibibazo byo mu bikoresho byo kubona no gutwara amaraso y'amaraso, cyane cyane iyo hakozwe ubushakashatsi bunini bwo kureba kugira ngo hamenyekane ingaruka z'inkingo no gukurikirana ubudahangarwa bw'umubiri.Nyamara, abantu bakingiwe berekana ibikorwa bya selile T birwanya SARS-CoV-2, birashobora gukuraho igihombo cya antibody kugirango bagabanye ubukana bwa COVID-1912,13.
Hano, twashatse kumva niba igipimo kimwe cy’ibisubizo by’akagari ka SARS-CoV-2 T gishobora guhanura ingaruka ziterwa n’indwara ya SARS-CoV-2 mu gihe cy’amezi 6 uhereye ku maraso, tutitaye ku mpamvu zitera ubudahangarwa bw'umubiri.Kugirango dukore ibizamini bya T selile byinjira cyane kandi bikurikizwa mubushakashatsi bunini, twagerageje no gukora ikizamini cya miniaturizasi kugirango gishobore gukorwa hifashishijwe urugero rwamaraso ya capillary.
Twapimye ubudahangarwa bw'umubiri ndetse no gusetsa mubaterankunga bazima dukoresheje gutahura hamwe ingirabuzimafatizo za SARS-CoV-2 T na antibodies za IgG zishingiye ku maraso y'amaraso yose (kubiranga abitabiriye amahugurwa, reba Werurwe 2022 14. Mu baterankunga bakingiwe, SARS-CoV-2- Ibisubizo byihariye bya T-selile byagenwe no gupima plasma interferon-IF (IFN-γ) nyuma yo guterwa amaraso yose hamwe na peptide ya SARS-CoV-2 (nkuko byari bisanzwe, reba 14,15,16,17,18) hamwe nibisubizo bya IgG bijyanye hamwe na nucleocapsid (N) yariyongereye mubatangaje ko banduye mbere, nubwo ibisubizo byombi byari byinshi mubaterankunga batakingiwe mbere banduye, umubare munini mu mubiri (Igishusho 1a, b). IgG ibisubizo birwanya spike glycoproteine ​​(RBD, S1, S2) bari hejuru cyane mu baterankunga bakingiwe mbere (Ishusho 1c - e).
igisubizo cya SARS-CoV-2 cyihariye IFN-γ + T ibisubizo byapimwe byapimwe nubushakashatsi bwuzuye bwamaraso kandi bushingiye ku rukingo rwabitabiriye ndetse nuburyo bwanduye bwa SARS-CoV-2 (byemejwe na PCR na / cyangwa ikizamini cyo gutembera) 'Vac + / Inf + 'n = 60 (icyatsi),' Vac + / Inf- 'n = 82 (ubururu),' Vac- / Inf + 'n = 4 (umuhondo),' Vac- / Inf- 'n = 1 (ntibikoreshwa).SARS-CoV-2 yihariye IgG ihuza reaction yibanda kuri nucleocapsid (“N”) (b; **** P <0.0001, ** P = 0.0016), indangururamajwi ihuza (“RBD”) (c; ** P = 0.0022, * P <0.015), spike subunit 1 (“S1”) (d; *** P = 0.0005, * (Vac + / Inf + na Vac + / Inf-) P = 0.022, * (Vac- / Inf + vs. cyangwa ikizamini cyo gutembera kuruhande) imiterere yanduye.'Vac + / Inf +' n = 60 (icyatsi), 'Vac + / Inf-' n = 71-82 (ubururu), 'Vac- / Inf +' n = 4 (umuhondo).Kugereranya kwakozwe hakoreshejwe ikizamini cya Kruskal-Wallis, gihindurwa kugereranya byinshi ukoresheje ikizamini cya Dunn.Ibyatanzwe byerekanwa nkimbonerahamwe (umurongo wo hagati kuri median, umupaka wo hejuru kuri 75th kwijana, umupaka wo hasi kuri 25%) hamwe na whiskers kumurongo ntarengwa kandi ntarengwa.Buri kadomo kagaragaza umuterankunga.Amakuru mabi atangwa muburyo bwa dosiye yibanze.
Nyuma yo gutoranya amaraso, abitabiriye amahugurwa basabwe kwipimisha raporo nziza ya PCR na / cyangwa ibisubizo byikizamini cya COVID-19;niba abitabiriye amahugurwa bapimye neza hagati ya 1 Nzeri 2021 na 29 Ukuboza 2021, bakekaga ko banduye Delta (B.1.617.2) variant coronavirus na Omicron (B.1.1.529) kugeza muri Leta zunze ubumwe za Amerika nyuma y’itariki ya 29 Ukuboza 2021, ubwo ubu buryo bwo guhangayika buba bwiganje.Mu baterankunga 148 basuzumwa, twabonye ko ubwandu bwa 26.3% (39/148) mu mezi 6 nyuma yo gutanga amaraso, 38 muri bo bakaba barabonye ikinini cya kabiri cyangwa icya gatatu cy’urukingo rwa COVID-19 (intambwe yanduye yabaye nyuma ya Pfizer / BioNTech ( BNT162b2) urukingo rwa mRNA cyangwa urukingo rwa AstraZeneca (ChAdOx1 nCoV-19));umuterankunga udakingiwe nawe yaranduye.Ubunini bwa SARS-CoV-2 yihariye IFN-γ-nziza ya T selile ibisubizo byagabanutse cyane mubatanze ikizamini cyiza cyo gusuzuma indwara ya COVID-19 kuruta abaterankunga batanduye (P <0.0001; Ishusho 2a), ahanini bitewe Kwinjiza neza ibisubizo bya T ukoresheje urukingo muri bamwe mubitabiriye amahugurwa (P = 0.050; Ishusho yinyongera 1).Nta sano ryari hagati yubunini bwa IFN-γ + T igisubizo cyakagari nigihe cyo kubona ibisubizo byiza bya COVID-19 (Ishusho yinyongera).Ibinyuranye, ntabwo RBD-, S1-, S2 ihuza IgG ibisubizo (Ishusho 2b - d) cyangwa RBD-, S1 itabogamye antibody ibisubizo byihariye kubwoko bwa gasozi cyangwa delta SARS-CoV-2 (B.1.617).) (Ishusho yinyongera. 3) irashobora gutandukanya abantu bafite ibyago byo kwandura.Nyamara, ibisubizo bike bya N-bihuza IgG kurwanya SARS-CoV-2 bifitanye isano n’ibyago byo kwandura COVID-19 (P = 0.0084; Ishusho 2e);abipimishije neza ntibashoboka 85% (P = 0.00035; CYANGWA 0.15, 95).% CI: 0.047–0.39 (Ishusho y'inyongera 4).
Amaraso y'amaraso atangwa n'abaterankunga bazima (n = 148) yasuzumye SARS-CoV-2 yihariye IFN-γ + T-selile ibisubizo (a; **** P <0.0001) no guhuza reseptor ya Spike na SARS-CoV yihariye. -2 gukangura.indangarugero (“RBD”) (b), spike 1 subunit (“S1 ″) (c), spike 2 subunit (“ S2 ″) (d), na nucleocapsid (“N”) (e; ** P = 0.0084) .Abitabiriye amahugurwa bapimishije COVID-19 (PCR na / cyangwa urujya n'uruza) bamenyekanye;kwandura kwose kwabaye mugihe cyamezi 6 uhereye kumaraso.Kugereranya kwakozwe hifashishijwe ikizamini cya Mann-Whitney.Ibyatanzwe byerekanwa nkimbonerahamwe (umurongo wo hagati kuri median, umupaka wo hejuru kuri 75th kwijana, umupaka wo hasi kuri 25%) hamwe na whiskers kumurongo ntarengwa kandi ntarengwa.Buri kadomo kagaragaza umuterankunga.ns ntabwo ari ngombwa.Ubushuhe f bwerekana urwego rwicumu rifitanye isano nimpinduka kuri dataset yagenwe.Kugereranya bitari bifite imibare ihambaye byakuwe muri matrix kandi byashyizweho na selile zidafite akamaro.Amakuru mabi atangwa muburyo bwa dosiye yibanze.
Isuzumabumenyi ryateganijwe ryagabanijwe rya 14 ryafatwaga nkubushake bwo gusuzuma ibyago byo kongera kwandura, bityo hashyizweho intera hagati y’imiterere kugirango hashyizweho ibipimo by’ingaruka zuzuye.Icyitegererezo cyibarurishamibare, cyarimo gusa ibihinduka byagize ingaruka zikomeye kubisubizo, byerekanaga ko ubunini bwa SARS-CoV-2 bwihariye IFN-γ + T bwakorewe selile aribwo buryo bukomeye bwo kwirinda indwara kugira ngo hamenyekane amahirwe y’umuntu ku giti cye yapimwe kuri COVID.-19 nziza (Igishusho 2f hamwe ninyongera Igishusho 4).Abarwayi bafite SARS-CoV-2 yihariye IFN-γ + T igisubizo cyakagari mugice cya gatatu (194-489 pg / ml IFN-γ) na kane (> 489 pg / ml IFN-γ) quartile 65% (P = 0.055; CYANGWA 0.35, 95% CI: 0.11–1.00) na 90% (P = 0.0050; CYANGWA 0.098, 95% CI: 0.014–0.42) bari bafite abitabiriye benshi.Amahirwe ni make (Ishusho yinyongera. 4).Muri rusange, abitabiriye amahugurwa ya SARS-CoV-2 yihariye ya T ituruka kumaraso yimitsi ≤79 pg / mL IFN-γ bafite ibyago 43.2% byo kwandura indwara mumezi 6, ugereranije nigisubizo> 489 pg / mL.ml ya IFN-γ yagize ibyago byo kwandura 5.4% (imbonerahamwe 2).
Kwipimisha amaraso kwamaraso bigarukira muburambe bitewe no gukenera icyitegererezo cya phlebotomiste.Kugirango hongerwe kuboneka T selile na IgG kwipimisha SARS-CoV-2, hashyizweho ubundi buryo bwo gupima amaraso ya capillary kugirango abitabiriye babone urugero rwamaraso yintoki murugo.Dukurikije ubumenyi dufite, nta raporo zabanjirije iyi zigeze zipima imikorere ya selile yihariye ya T mu maraso ya capillary.Isano rikomeye ryerekanwe mbere hagati ya lymphocyte ziboneka hakoreshejwe capillary igereranijwe hamwe namaraso yimitsi.Byongeye kandi, byavuzwe ko ubushakashatsi bushingiye ku maraso bupima SARS-CoV-2 yihariye ya T bwakoresheje T selile ikoresha 320 μL gusa y’amaraso y’imitsi, 20 ikuraho impungenge ziterwa ninshuro za selile progenitor T mu maraso ya capillary.
Twifashishije ubu buryo bwisanzuye busanzwe bufatika bwa selile ya SARS-CoV-2 T na antibodies ya IgG dushingiye kumaraso ya capillary yose kugirango tupime ubudahangarwa bw'umubiri ndetse no gusetsa abitabiriye amahugurwa hamwe nibibazo bitandukanye ndetse no gukingira / kwandura (Imbonerahamwe 1).bashakishijwe baturutse mu Bwongereza hagati ya 24 Mutarama na 14 Werurwe 202214. Benshi (90.9%) by'intangarugero z'intoki babonetse neza kandi boherezwa muri laboratoire mu masaha 24 yo gukusanya.Rimwe na rimwe wasangaga ibyitegererezo byakiriwe mu masaha 48 nyuma yo kuvoma amaraso, ariko nta na hamwe muri ubwo buryo bwatsinze igenzura ry’ubuziranenge kandi ntibwagize ingaruka ku bipimo rusange bya T cyangwa antibody (Ishusho yinyongera 5).Nubwo hari itandukaniro mubunini bwa SARS-CoV-2 yihariye ya selile IFN-γ + T yapimwe mubipimo byamaraso ya capillary na venine mubantu bamwe, nta tandukaniro ryibanze ryagaragaye muri rusange (P = 0.88; Ishusho yinyongera 6 ).).
SARS-CoV-2 yihariye ya IFN-γ + T ibisubizo by'akagari byiyongereye cyane ku bantu bakingiwe na bo bavuze ko banduye mbere (P = 0.0001), ariko ntibiri hejuru cyane ugereranije n'abaterankunga batakingiwe mbere (P = 0.19, Ishusho. 3a).).IgG ibisubizo birwanya spike glycoproteine ​​(RBD, S1, S2) byari hejuru cyane mubaterankunga bakingiwe kurusha abaterankunga batakingiwe, hatitawe ku kwandura mbere (Ishusho 3b-d).Igishimishije, igisubizo hagati ya N-IgG igisubizo cyari kinini mubitabiriye mbere batanduye inkingo ugereranije nabitabiriye inkingo, nubwo ibyo bitageze ku kamaro (Ishusho 3e).Mu baterankunga batakingiwe kandi batanduye biyitiriye ubwabo, 15 kuri 37 (40.5%) bitabiriye amahugurwa bahisemo N-ihuza IgG, hejuru y’urugero rwashyizweho mbere ya 2.0 BAU / mL14;aba 15 bitabiriye amahugurwa Cumi na babiri muri abo barwayi bapimwe neza ko IFN-γ + T yakiriye selile hejuru y’urugero rwashyizweho mbere ya 22.7 pg / mL IFN-γ14.Kubwibyo, birashoboka ko abitabiriye aya mahugurwa mbere banduye SARS-CoV-2 kandi ntibapimwe COVID-19 kubera guhitamo kwawe, kubura PCR na / cyangwa ibikoresho bitemba, cyangwa ntibabimenyeshejwe.Nubwo hari isano rikomeye hagati y ibisubizo bya T selile kuri IFN-γ + na N-ihuza IgG murwego rwabaterankunga batakingiwe (P = 0.0044; Igishushanyo cyinyongera, igisubizo cya N-IgG cyagabanutse vuba kuruta igisubizo cya N-IgG, naho IFN-γ + T selile yagumishijwe hatitawe kumiterere yinkingo, nubwo umubare wabaterankunga mubyumweru 50 nyuma yikibazo cyari gito (Umugereka winyongera.) selile hamwe na RBD bifitanye isano, nubwo abitabiriye amahugurwa bakiriye inshuro ebyiri za BNT162b2 bakurikirwa no gukingirwa kwa mRNA1273 berekanye urwego rwisumbuyeho rwa selile IFN-γ + T bumvise cyane SARS-CoV-2 kurusha abahawe dosiye ebyiri za ChAdOx1 na BNT162b2 (Inyongera Igicapo 9) Byongeye kandi, raporo zavuzweho zagize itandukaniro rito muri rusange mubisubizo bya T byagaragaye ugereranije nabaterankunga bazima (Ishusho yinyongera 10).
igisubizo cya SARS-CoV-2 cyihariye IFN-γ + T ibisubizo byapimwe byapimwe nubushakashatsi bwakozwe bwamaraso yose kandi bushingiye kumukingo wabitabiriye ndetse nuburyo bwanduye bwa SARS-CoV-2 (byemejwe na PCR na / cyangwa ikizamini cyo gutembera kuruhande).'Vac + / Inf +' n = 42 (icyatsi), 'Vac + / Inf-' n = 158 (ubururu), 'Vac- / Inf +' n = 33 (umuhondo), 'Vac- / Inf-' n = 37 (imvi).**** P <0.0001, *** P = 0.0001, * (Vac + / Inf- na Vac- / Inf-) P = 0.045, * (Vac- / Inf + na Vac- / Inf-) P = 0.014 .SARS-CoV-2 yihariye IgG ihuza ibisubizo kuri spike reseptor ihuza domaine (“RBD”) (b; **** P <0.0001, ns: ntabwo ari ngombwa), subike subike 1 (“S1”) (c; * * ** P <0.0001, ns: ntabwo ari ngombwa), spike subunit 2 (“S2 ″) (d; **** P <0.0001, *** P = 0.0005, * P = 0.016) na nucleocapsid (“ N ”) (e; **** P <0. imiterere.'Vac + / Inf +' n = 46 (icyatsi), 'Vac + / Inf-' n = 182 (ubururu), 'Vac- / Inf +' n = 34 (umuhondo), 'Vac- / Inf-' n = 37 (imvi).Kugereranya kwakozwe hakoreshejwe ikizamini cya Kruskal-Wallis, gihindurwa kugereranya byinshi ukoresheje ikizamini cya Dunn.Ibyatanzwe byerekanwa nkimbonerahamwe (umurongo wo hagati kuri median, umupaka wo hejuru kuri 75th kwijana, umupaka wo hasi kuri 25%) hamwe na whiskers kumurongo ntarengwa kandi ntarengwa.Buri kadomo kagaragaza umuterankunga.Amakuru mabi atangwa muburyo bwa dosiye yibanze.
Nkubwa mbere, abitabiriye amahugurwa basabwe gutanga raporo nziza ya PCR na / cyangwa ibisubizo byamaraso ya COVID-19;Ikigo cy’ubuzima cy’Ubwongereza kivuga ko abitabiriye amahugurwa bakekwagaho kuba baranduye Omicron coronavirus (B.1.1.529) mu gihe cyo gupima virusi itera virusi, kuko ari yo yari yiganje mu Bwongereza mu gihe cyo kwiga.Mu baterankunga 299 basuzumwa, twabonye igipimo cyanduye cya 8.0% (24/299) mu mezi atatu nyuma yo gutanga capillary, barindwi muri bo ntibakingiwe.Umubare w'ingaruka mbi mu bitabiriye amahugurwa bose wari muke mu bapimishije COVID-19 (10.7%) ugereranije n'abapimishije COVID-19 (24.4%, Imbonerahamwe 1), ibyo bikaba bishobora guterwa n'uko abitabiriye amahugurwa bamwe indwara ziritonde kandi zirinde ingaruka zishobora kubaho nka diyabete na kanseri.Nkuko bigaragara mu maraso y’imitsi, SARS-CoV-2 yihariye interferon-γ (IFN-γ) -uturemangingo T twapimye mu maraso ya capillary y’abantu batanze ikizamini cyiza cyo gusuzuma COVID-19.Ubunini bwibisubizo bwari hasi cyane ugereranije nabaterankunga batanduye (P = 0.034; Igicapo 4a) kubera ko ugereranije no kwinjizwa nabi kwakagari ka T ukoresheje urukingo na / cyangwa kwandura mbere (Ishusho yinyongera 11).Mu buryo nk'ubwo, ntabwo RBD-, S1-, S2 ihuza IgG ibisubizo (Ishusho 4b - d) cyangwa RBD-, S1 itabogamye antibody ibisubizo byihariye kubwoko bwa gasozi cyangwa delta SARS-CoV-2 (B. 1.617).(Ishusho yinyongera 12).Abantu bafite ibyago byose byo kwandura barashobora kumenyekana.Bitandukanye na cohort yimitsi, ibisubizo bya N bifitanye isano na IgG nabyo ntibitandukanya ibyago bya COVID-19 (Igicapo 4e), byerekana ko variant ya Omicron (B.1.1.529) yongerera ubudahangarwa bw'umubiri kubantu banduye mbere, nkuko biherutse gusobanurwa 21. Ibinyuranye, imbaraga za SARS-CoV-2 zihariye IFN-γ T igisubizo cyongeye kuba impinduka zingenzi muguhitamo itandukaniro ryikizamini cya COVID-19 (Ishusho 4f).Muri rusange, abitabiriye amahugurwa ya SARS-CoV-2 yihariye ya capillary T-selile ≤ 23.7 pg / mL IFN-γ bafite ibyago byo kwandura 14.9% mumezi atatu ugereranije nigisubizo> 141,6 pg / mL.ml IFN.-γ yagize ibyago byo kwandura 4.4% (Imbonerahamwe 2).
IFN-γ + T ibisubizo by'akagari byihariye kuri SARS-CoV-2 (a; * P = 0.034) na SARS-CoV-2 yihariye IgG igenewe reseptor-ihuza indangarubuga (“RBD”) (b), spike subunit 1 (' S1 ′) (c), spike subunit 2 ('S2 ′) (d) na nucleocapsid ihuza reaction (' N ') (e).Abitabiriye amahugurwa bagaragaje ko ari byiza mu bizamini bya COVID-19 (PCR na / cyangwa ikizamini cyo gutembera kw'amaraso), indwara zose zabaye mu mezi 3 nyuma yo gupimwa amaraso.Kugereranya kwakozwe hifashishijwe ikizamini cya Mann-Whitney.Ibyatanzwe byerekanwa nkimbonerahamwe (umurongo wo hagati kuri median, umupaka wo hejuru kuri 75th kwijana, umupaka wo hasi kuri 25%) hamwe na whiskers kumurongo ntarengwa kandi ntarengwa.Buri kadomo kagaragaza umuterankunga.ns ntabwo ari ngombwa.Ubushuhe f bwerekana urwego rwicumu rifitanye isano nimpinduka kuri dataset yagenwe.Kugereranya bitari bifite imibare ihambaye byakuwe muri matrix kandi byashyizweho na selile zidafite akamaro.Amakuru mabi atangwa muburyo bwa dosiye yibanze.
Mugihe tujya mu cyiciro gikurikira cy’icyorezo cya COVID-19, intego izibanda ku gukumira no gucunga ibyago ku giti cyabo no kumenya abanyamuryango batishoboye.Gushiraho ihuriro ry’ubudahangarwa kuri COVID-19 ni ngombwa kugirango umenye neza kandi uvure ayo matsinda afite ibyago byinshi.Ubu hari ibimenyetso byinshi byerekana ko ubudahangarwa bwa T-selile burinda ubwandu bwa SARS-CoV-2 kandi bugabanya ubukana bwa COVID-1910.Amakuru yatanzwe hano yerekana ko imbaraga za SARS-CoV-2 zihariye IFN-γ + T selile zisubiza spike, membrane, na nucleocapsid proteine ​​zubaka zitanga uburinzi bukomeye kuri COVID-19 kuruta guhuza antibody.19 biteza imbere cyangwa bitesha agaciro ibisubizo .kandi bigomba kwitabwaho mugihe cyo gusuzuma ubudahangarwa bwa buri muntu na / cyangwa ubushyo.Virusi ya RNA nka SARS-CoV-2 cyangwa ibicurane bya grippe A (IAV) birinda kutabogama kwa serologiya mu buryo bwihuse bwihuse epitopes B-selile igaragara kuri antigene zo hejuru zemewe na antibodies.Kurinda ubudahangarwa bw'umubiri bitangwa na selile T birashobora kwerekana intego ya epitopes ituruka mu turere twinshi twabitswe na poroteyine za virusi zidashobora guhita zihunga ubudahangarwa bw'umubiri.Kurinda T selile-medrated kurinda ibishya SARS-CoV-2 bisa nuburinzi bwa heterosubtypic bwunganirwa na T selile yibasira poroteyine zabitswe ziboneka muri IAV22,23.
Nubwo hari imbaraga nini zo gupima ubudahangarwa bw'umubiri kuri COVID-19, ugereranije ni gake hitabwa ku iterambere ry’ukuri, ryinjira cyane, risanzwe rya T-selile.Ingorabahizi gakondo hamwe nigiciro kijyanye no gupima ibisubizo by'utugari T bibuza kumenya neza ubudahangarwa bwa T mugihe cyo gusuzuma ubudahangarwa bw'abaturage benshi.Mugihe ubushakashatsi bwinshi bwamaraso peptide yubushakashatsi bwakozwe vuba aha, buriwese arasaba phlebotomiste kubona amaraso, bikagabanya kuboneka nubunini.Sisitemu y'amaraso ya capillary ikoreshwa cyane kugirango hamenyekane ubwinshi bwa antibodiyite za SARS-CoV-2 mu baturage.Twahinduye amaraso ya capillary kugirango dukore ubushakashatsi bwuzuye bwamaraso peptide kugirango dusuzume reaction ya T selile ya proteine ​​zubaka za SARS-CoV-2 hamwe na SARS-CoV-2 ibisubizo byihariye bya antibody.Mubyukuri, gupima hamwe kwa SARS-CoV-2 yihariye antibodiyite na selile T muburyo bumwe bwamaraso ya capillary birashimishije cyane: (i) bigabanya gukenera kwipimisha amaraso menshi kubitabiriye amahugurwa, (ii) bizamura uburambe bwabitabiriye no gusobanukirwa;(iii) kunoza ibikoresho no kugabanya kwigana, (iv) kugabanya ingaruka z’ibidukikije kuko ibikenerwa muri laboratoire no gutanga icyitegererezo bisabwa.Nubwo muri rusange IFN-γ reaction yari isa hagati y’amaraso y’amaraso ahuye na capillary, byagaragaye ko ari hasi mu gice cy’amaraso ya capillary yabitabiriye (Ishusho 4a) ugereranije n’amaraso y’amaraso (Ishusho 2a).IFN-γ indangagaciro Hariho ibisobanuro byinshi kuri ubu bushakashatsi, aribyo, umubare munini w'abitabiriye amahugurwa hamwe n'ingaruka zisaba ubuvuzi bwa immunosuppressive binjijwe mu itsinda rya capillary blood sampling cohort (Imbonerahamwe 1) na Viability na / cyangwa imikorere ya selile T yavuye mu mitsi. ibyitegererezo birashobora kuba bike, cyane cyane urebye imiterere yo kubika igihe kirekire kuburugero mbere yo gutera peptide.
Kugeza ubu urukingo rwa COVID-19 rutanga uburyo bwiza bwo kwirinda indwara zikomeye ku bahabwa benshi mu mezi 6 nyuma yo gukingirwa8.Igishimishije, nubwo inkingo mbi iterwa na serologiya itabogamye ya SARS-CoV-26,7, ibisubizo bya T-selile byatanzwe no gukingirwa ubwoko bwa SARS-CoV-2 byakomeje kuba byiza cyane, kuko abandi 25 bagaragaye.Amakuru twerekanye hano yerekana akamaro ko gusuzuma mu buryo bwagutse gusuzuma ubudahangarwa bw'inkingo, bikagaragaza inkingo zifite ubudahangarwa bwa T-selile zidahagije kugira ngo wirinde kwandura gitunguranye no kwanduza virusi.Twabonye kandi ko abantu benshi batakingiwe binjiye mu mutwe wa capillary bagize igisubizo gikomeye cy’utugingo ngengabuzima twa SARS-CoV-2 (na N-binding IgG) tutitaye ku nkingo zabanjirije iyi, bikaba bishoboka ko biterwa no kwandura mbere.Aho gukingiza abantu babikwiye, ibyago byabo byo kwandura bigomba gusuzumwa hashingiwe ku miterere y’ikingira ryabo hamwe n’amahitamo abimenyeshejwe.
Intambamyi z’ubu bushakashatsi zirimo kwemeza ko abitabiriye ubwabo ubwabo banduye ko banduye SARS-CoV-2 nyuma yo gukusanya amaraso kugira ngo bamenye akamaro k’ubudahangarwa;abitabiriye amahugurwa bamwe bashobora kwandura ibimenyetso kandi ntibashobora kwipimisha PCR na / cyangwa kuruhande rwa COVID-19.Dataset yacu yabuze kandi amakuru yerekeye imiti yabitabiriye mugihe cyo gupima amaraso.Byongeye kandi, urebye ko abitabiriye amahugurwa bose bagaragaje gusa ibimenyetso byoroheje / bitagereranywa cyangwa nta bimenyetso, ntabwo byashobokaga kumenya ibisubizo by’ubudahangarwa bivuye mu makuru yacu yahanuye ko ibyago by’indwara zikomeye ndetse n’ibitaro bya COVID-19.Ariko, kuba CD8 + T ibisubizo bya selile birwanya epitoces yihariye ya nucleocapsid biherutse guhuzwa no kurinda COVID-1926.Byongeye kandi, ubushakashatsi bwakoreshejwe hano ntabwo bwapimye ibisubizo bya selile T kuri proteine ​​zihariye zagaragajwe hakiri kare za SARS-CoV-2 zidafite imiterere-karemano ziherutse kugaragara ko zegeranya cyane cyane mu bakozi b’ubuzima bwa seronegative bagiye bahura n’abarwayi banduye.Hashingiwe kuri iki gikorwa, urebye ubwinshi bw’ubwandu bw’abaturage mu gihe cyo gushaka abakozi kandi bikaba bishoboka cyane ko abantu bandura virusi, umubare w’utugari twa SARS-CoV-2 T twabonetse mu bizamini byacu nawo bigaragara ko ushoboye gukuraho.kwandura subclinical muri cohort zacu.Hanyuma, ntabwo twapimye umusaruro wa interleukin 2 na selile T kuko akazi kacu kambere kagaragaje kutamenya neza ibisubizo bya T-selile ya SARS-CoV-214, nubwo ibisubizo byihariye bya IL-2 bishobora kwerekana mbere-reaction-reaction.selile zijyanye no kwirinda indwara ya SARS-CoV-211.
Ufatiye hamwe, aya makuru yerekana icyifuzo gikenewe cyubushakashatsi bwigihe kirekire bwinjizamo SARS-CoV-2 yihariye T ibisubizo byingirabuzimafatizo mu ngamba z’ubudahangarwa bw’abaturage.Izi mbaraga zishobora gufashwa niterambere ryikizamini gishya cyamaraso apima T-selile.
Umushinga w’ubushakashatsi wasabye abitabiriye amahugurwa kuva muri Gashyantare 2021 kugeza muri Werurwe 2022. Itsinda ry’abaterankunga bazima (n = 148) batanze urugero rw’amaraso y’imitsi yari agizwe ahanini n’abakozi ba kaminuza n’abanyeshuri bitabiriye serivisi yo gusuzuma COVID-19 ya kaminuza ya Cardiff cyangwa abakozi bo mu ishuri ribanza muri Cardiff.Abitabiriye amahugurwa bose bari bafite ubuzima bwiza kandi ntibigeze batangaza ko bafashe imiti ikingira indwara (reba Imbonerahamwe 1 kubiranga).Itsinda ryabitabiriye batanze urugero rwamaraso ya capillary harimo abaterankunga bose kubushake (bafite imyaka 18+) baturutse mubwongereza.Hagati ya 24 Mutarama na 14 Werurwe 2022, 342 bitabiriye ubwo bushakashatsi, muri bo 299 batanze laboratoire y'amaraso.Abenshi mu bitabiriye amahugurwa bakomeje kutakingirwa kandi / cyangwa bagaragaje ingaruka zikomeye, harimo indwara ziterwa na autoimmune na kanseri (reba Imbonerahamwe 1 kubiranga).Ubu bushakashatsi bwakiriwe neza na komite ishinzwe imyitwarire yubushakashatsi bwa Newcastle na Tyneside ya 2 (ID IRAS: 294246) hamwe na komite ishinzwe imyitwarire y’ubushakashatsi bw’ubuvuzi bwa kaminuza ya Cardiff (SREC ref: SMREC 21/01).Abitabiriye amahugurwa bose batanze uruhushya rwanditse mbere yo kubishyiramo.Abitabiriye amahugurwa nta ndishyi bahawe kubera ko bitabiriye ubu bushakashatsi.
Amaraso y'amaraso yabonetse hakoreshejwe venipuncture muri litiro 6 cyangwa 10 za litiro cyangwa sodium heparin vacutainers (BD).Amaraso ya capillary yabonetse akoresheje urutoki hanyuma akusanyirizwa muri microcontainers ya heparin (BD).Nibura byibuze 400 µl yamaraso;icyitegererezo icyo aricyo cyose kiri munsi yaya mafranga azangwa.Izindi mpamvu zo kwangwa ntangarugero zirimo coagulation nini na / cyangwa hemolysis no kunanirwa gukusanya plasma ya viscous yo gusesengura (Ishusho yinyongera 5).Amaraso 299 yuzuye ya capillary yabonetse kugirango asuzume ibisubizo bya antibody, muribyo 270 byanabonetse mugusuzuma ibisubizo bya selile T.
SARS-CoV-2 ibisubizo byihariye bya T selile byasuzumwe hifashishijwe COVID-19 Immuno-T (ImmunoServ Ltd) kandi byakozwe nkuko byasobanuwe mbere14.Muri make, ml 6 imwe cyangwa ml 10 ya sodium heparin (BD) ya voutainer yakuwe kuri buri wese mu bitabiriye amahugurwa hanyuma itunganyirizwa muri laboratoire mu masaha 12 nyuma yo gukusanya amaraso.Nubwo ingero nyinshi zatunganijwe mu masaha 24, amaraso ya capillary ya 400-600 μl heparinize (BD) yakusanyirijwe mu masaha 48 nyuma yo guterwa urutoki.Amaraso ya Venusi na / cyangwa capillary yatewe hamwe nibidendezi bitandukanye bya peptide yihariye ya SARS-CoV-2 (ubwoko bwubwoko bwa gasozi) nkuko byasobanuwe mbere14.Iri somero rya peptide ririmo urutonde rwa 420 15-mer hamwe na aside 11 yuzuye aminide ikwirakwiza poroteyine zose (S1 na S2) (S; poroteyine ya NCBI: QHD43416 1), nucleocapsid phosphoprotein (NP; poroteyine ya NCBI: QHD43423 2) na membrane glycoproteine ​​(M) ; Poroteyine ya NCBI: QHD43419 1) ikurikirana rya code (byitwa “S- / NP- / M-isomero rya peptide isomero”).Peptide zose zasukuwe kugeza kuri> 70%, zishonga mumazi meza kandi zikoreshwa mugihe cyanyuma cya 0.5 μg / ml kuri peptide.Ingero zashyizwe kuri 37 ° C mumasaha 20-24.Imiyoboro noneho yashizwemo 5000 × g muminota 3 hanyuma ~ 150 µl ya plasma yakusanyirijwe hejuru ya buri cyitegererezo cyamaraso.Bika icyitegererezo cya plasma kuri -20 ° C mugihe cyukwezi kumwe mbere yo gukora cytokine / antibody detection.
IFN-γ yapimwe hifashishijwe IFN-γ ELISA MAX Deluxe Set (BioLegend, catalog numero 430116) kandi ikorwa ukurikije amabwiriza yabakozwe.Ako kanya nyuma yo guhagarika igisubizo (2N H2SO4) hiyongereyeho, microplate yasomwe kuri 450 nm ukoresheje umusomyi wa plaque ya BioLegend Mini ELISA.IFN-γ yagereranijwe nuburyo busanzwe bwo gutandukanya ibicuruzwa ukoresheje GraphPad Prism.Indangagaciro ziri munsi yimipaka yo hasi yipimishije yanditsweho 7.8 pg / ml, agaciro kari hejuru yumupaka wo hejuru wibisobanuro byanditse nka 1000 pg / ml.
Antibodiyite zirwanya SARS-CoV-2 RBD / S1 / S2 / N IgG zapimwe hakoreshejwe Bio-Plex Pro Human IgG SARS-CoV-2 4-plex panel (Bio-Rad, injangwe no 12014634) kandi yanditseho ukurikije amabwiriza yabakozwe.amabwiriza.Ingero zerekana agaciro hejuru yumubare wibipimo byongeye gusubirwamo kuri 1: 1000.Impuzandengo ya fluorescence ubukana bw'amasaro yapimwe ku gikoresho cya Bio-Plex 200 (Bio-Rad).Antibody yibanze yabazwe na VIROTROL SARS-CoV-2 igenzura rimwe (Bio-Rad) hanyuma ihinduka OMS / NIBSC 20/136 International Reference Standard Units (BAU / mL) ukoresheje ibintu bya kalibrasi yabakozwe.
RBD na S1 subunit yihariye itesha agaciro antibodiyite zirwanya SARS-CoV-2 zo mu bwoko bwa delta na delta (B.1.617) Imirongo ya SARS-CoV-2 yapimwe hifashishijwe Bio-Plex Pro Human SARS-CoV-2 Antibody Kit (Bio) -Rad, igice no 12016897), ukurikije amabwiriza yabakozwe.Gupima impuzandengo ya fluorescence kuri Bio-Plex 200 (Bio-Rad) hanyuma ubare ijanisha ryabujijwe (ni ukuvuga kutabogama) ukoresheje formula ikurikira:
Kwanduza kwanduza kwanduza SARS-CoV-2 byakozwe nkuko byasobanuwe mbere28.Muri make, 600 PFU yubwoko bwa SARS-CoV-2 yashyizwemo inshuro 3 zikurikirana za plasma zibiri muri duplicate kumasaha 1 kuri 37 ° C.Uruvange noneho rwongewe muri selile VeroE6 mumasaha 48.Monolayers yakosowe na 4% ya paraformaldehyde, ihindurwamo 0.5% NP-40 hanyuma ishyirwa mumasaha 1 muguhagarika buffer (PBS irimo 0.1% hagati ya 3% n'amata asukuye).Antibody yibanze (anti-nucleocapsid 1C7, Stratech) yongewemo muguhagarika buffer kumasaha 1 mubushyuhe bwicyumba.Nyuma yo gukaraba, antibody ya kabiri (anti-imbeba IgG-HRP, Pierce) yongewemo muguhagarika buffer kumasaha 1.Monolayers yarogejwe, itezwa imbere ikoresheje Sigmafast OPD hanyuma usome kumusomyi wa plaque Clariostar Omega.Iriba idafite virusi, idafite virusi ariko idafite antibodi, na sera isanzwe yerekana ibikorwa hagati yashyizwe muri buri igeragezwa nkigenzura.
Isesengura mibare ryakozwe muri GraphPad Prism (verisiyo 9.4.1).Ubusanzwe amakuru yashyizweho yageragejwe hakoreshejwe ikizamini cya Shapiro-Wilk.Ibipimo bitari ibipimo byakoreshejwe kubigereranya byose.Ikizamini cya Mann-Whitney cyakoreshejwe kuburugero rudakorewe.Ibizamini byose byari impande zombi hamwe numubare wingenzi wa P ≤ 0.05.
Isesengura ryambere ryubushakashatsi bwa dataset ryakozwe muri R (verisiyo 4.0.3).Ibi bikubiyemo iterambere rya Spearman univariate urwego ruhuza matrix, aho ihuriro riri hagati yimpinduka ebyiri ryerekanwa nubunini namabara ya kare.Ubusobanuro bwibarurishamibare hagati yamashyirahamwe bwabazwe hakoreshejwe rho ya Spearman, aho indangagaciro ≤0.05 zabonwaga ko ari ngombwa.Kugereranya bitari bifite imibare ihambaye byakuwe muri matrix kandi byashyizweho na selile zidafite akamaro.P-indangagaciro zahinduwe kubigereranya byinshi ukoresheje ubugororangingo bwa Holm.Ikibiri cya logistic regression cyakoreshejwe mukugereranya ingaruka zimpinduka muri dataset kubisubizo byiza kuri COVID-19.IFN-γ T ibisubizo bya selile hamwe na anti-RBD / S1 / S2 / N IgG amanota ya titer yahinduwe mubintu, aho buri muntu yahawe quartile ikwiye kuri buri manota.Nyuma yibyo, icyitegererezo cyambere cyubushakashatsi cyateguwe hifashishijwe imikorere ya glm muri pake y'ibarurishamibare (V4.0.3).Ikigereranyo kidasanzwe gikomoka kuri ubu buryo bwumwimerere cyakuwe muri coefficient yicyitegererezo ukoresheje imikorere ya 'odd_plot' mumikorere ya OddsPlotty (V1.0.2).Mugihe dutezimbere icyitegererezo cyo kwemeza, twakoresheje imikorere ya "bestglm" kuva muri pack ya bestglm (V0.37.3) kugirango tugabanye kubogama kubakoresha no kwemeza ko igice cyiza cyabahanuzi gishobora gutoranywa.Uburyo bwatoranijwe bwari "bwuzuye" kandi igipimo cyamakuru yakoreshejwe mugusuzuma icyitegererezo gikwiye ni AIC.Igikorwa kimwe cyasobanuwe haruguru cyakoreshejwe kugirango ubone igipimo kidasanzwe.
Kubindi bisobanuro kubijyanye nigishushanyo mbonera cyo kwiga, reba ubushakashatsi bwibidukikije bujyanye niyi ngingo.
Inzandiko no gusaba ibikoresho bigomba koherezwa kwa Dr. Martin Scarr cyangwa Porofeseri Andrew Godkin.Iyi ngingo itanga amakuru yumwimerere.
Kode ya R ikoreshwa mugukora imiterere yimibare iraboneka kumugaragaro nta gusaba29.Gusubiramo amakuru nimpushya urashobora kubisanga kuri www.umuco.com/ibisobanuro.
Munro, APS n'abandi.Umutekano nubudahangarwa bwinkingo ndwi za COVID-19 nkumuti wa gatatu (booster) nyuma yinshuro ebyiri za ChAdOx1 nCov-19 cyangwa BNT162b2 (COV-BOOST) mubwongereza: icyiciro cya 2, gihumye, multicentre, cyateganijwe, kigenzurwa.Lancet 398, 2258–2276 (2021).
Stewart, ASV n'abandi.Ubudahangarwa bw'umubiri, umutekano, hamwe na reactogenicity yo gukingira ibanze rya COVID-19 (Com-COV2) ukoresheje mRNA, virusi ya virusi, hamwe ninkingo za poroteyine zunganira mu Bwongereza: icyiciro cya 2, impumyi imwe, ibizamini byateganijwe, ikizamini kidakabije.Lancet 399, 36–49 (2022).
Lee, ARIB n'abandi.Ingaruka z'inkingo za COVID-19 mu barwayi badafite ubudahangarwa: Isubiramo rifatika na Meta-Isesengura.BMJ 376, e068632 (2022).
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