Abubuwan sinadaran bakin karfe 347 Girman venous ko jini na capillary, musamman don SARS-CoV-2, martanin T-cell yana ƙayyade rigakafi ga COVID-19.

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347 bakin karfe sinadaran abun da ke ciki

Bakin Karfe 347 Coil Tube Chemical Composition

A sinadaran abun da ke ciki da kuma inji Properties na bakin karfe 347 coil tube ne kamar haka:
Carbon - 0.030% max
Chromium - 17-19%
Nickel - 8-10.5%
Manganese - 1% max

Bakin Karfe 347 Coil Tube Mechanical Properties

Dangane da Bakin Karfe 347 Coil Tube Manufacturer, Mechanical Properties na 347 Coil Tube:
- Ƙarfin Ƙarfi (psi) - 75,000 min
- Ƙarfin Haɓaka (psi) - 30,000 min
- Tsawaita (% a cikin 2 ″) - 25% min
Brinell Hardness (BHN) - 170 max

Aikace-aikace & Amfani da Bakin Karfe 347 Coil Tube

• Bakin Karfe 347 Coil Tube Ana amfani dashi a cikin Sugar Mills.
• Bakin Karfe 347 Coil Tube Ana amfani dashi a cikin Taki.
• Bakin Karfe 347 Coil Tube Ana amfani dashi a Masana'antu.
• Bakin Karfe 347 Coil Tube da aka yi amfani da shi a Shuka wutar lantarki.
• Bakin Karfe 347 Coil Tube Amfani da Abinci da Kiwo.
• Bakin Karfe 347 Coil Tube da ake amfani da shi a Shuka Mai da Gas.
• Bakin Karfe 347 Coil Tube Manufacturer wanda aka yi amfani da shi a Masana'antar Ginin Jirgin ruwa.

Ana tunanin takamaiman ƙwayoyin T na SARS-CoV-2 don kariya daga kamuwa da cuta da ci gaban COVID-19, amma babu wata shaida kai tsaye ga wannan.Anan, mun kwatanta duka ma'aunin jini na SARS-CoV-2-takamaiman interferon-γ tabbataccen sel T tare da ingantaccen sakamakon gwajin COVID-19 (PCR da/ko kwarara ta gefe) a cikin watanni 6 na tarin jinin Lian.Daga cikin mahalarta 148 da suka ba da gudummawar samfuran jini na venous, girman amsa ta musamman ta kwayar cutar SARS-CoV-2 ta kasance mafi girma a cikin waɗanda ke da kariya fiye da waɗanda suka kamu da cutar (P <0.0001).% haɗarin kamuwa da cuta, yayin da babban ƙarfi ya rage wannan haɗarin zuwa 5.4%.Waɗannan sakamakon an haɗa su zuwa ƙarin mahalarta 299 waɗanda suka gwada gwajin jini mai ƙima wanda zai iya sauƙaƙe samun damar yin amfani da bayanan rigakafi na T-cell na yawan jama'a (14.9% vs. 4.4%).Don haka, auna ƙwayoyin T na musamman don SARS-CoV-2 na iya yin hasashen haɗarin kamuwa da cuta kuma yakamata a kimanta shi yayin sa ido kan matsayin garkuwar mutum da yawan jama'a.
Aunawa da fahimtar martanin rigakafi ga kamuwa da cutar ta SARS-CoV-2 yana da mahimmanci don haɓaka ingantattun dabaru na gaba don rage lafiyar jama'a da tasirin tattalin arzikin barkewar COVID-19 na gaba.Gano abubuwan da ke da alaƙa da rigakafi zai ba da mahimman bayanai game da haɗarin yawan jama'a ga kamuwa da cuta, mai yuwuwa faɗakarwa da wuri na asibiti kololuwa, da kuma ba mutane damar da kansu su sarrafa haɗarin kamuwa da cuta da haɗarin kamuwa da wasu.Sa ido kan rigakafi ya tabbatar da mahimmanci don kimanta tasirin rigakafin COVID-19 a cikin lafiyayyen marasa lafiya da masu haɗari 1,2,3 musamman a cikin ƙwayoyin cuta na SARS-CoV-24, kuma gano ƙarancin rigakafi zai haifar da buƙatar haɓaka rigakafi Yi allurar rigakafi da hanawa. annobar nan gaba .
Matsayin rigakafi na mutum zuwa kamuwa da cuta ta SARS-CoV-2 ya dogara da dalilai da yawa: nauyin hoto na hoto a lokacin bayyanar, bambance-bambancen ƙwayoyin cuta, shekaru, yanayin alurar riga kafi / kamuwa da cuta, cututtuka, magunguna, kuma mafi mahimmanci, kamuwa da cutar SARS-CoV .2 amsawar rigakafi mai daidaitawa yana faruwa a lokacin bayyanar cutar5.Kimanta martanin rigakafin rigakafi ga kamuwa da cuta ta SARS-CoV-2 da/ko allurar rigakafi ya mai da hankali kan kididdigar serological waɗanda ke auna kasancewar ƙwayoyin rigakafi na musamman don gina jiki (misali spike glycoprotein).Koyaya, kasancewar ko rashi na ƙwayoyin rigakafi kaɗai ba ya ƙayyade daidaitaccen martanin rigakafin rigakafi, saboda ana rage martani sosai akan lokaci6 da kuma kawar da bambance-bambancen SARS-CoV-2 a cikin murmurewa ko masu allurar rigakafin sau biyu Rauni aiki, wanda zai haifar da babban aiki. yawan kamuwa da cututtuka7.Tabbas, kariya daga alamun COVID-19 da Omicron bambance-bambancen (B.1.1.529) ya haifar zuwa kusan 10% bayan watanni 4-6 kawai na rigakafin mRNA, kodayake kariya daga cutar mai tsanani ta ci gaba> 68% na akalla watanni 78.Matsakaicin amsawar ƙwayoyin sel T masu daidaitawa, waɗanda ke ba da kariya ta dogon lokaci daga kamuwa da cuta, ita ce mafi kyawun alamar kamuwa da kamuwa da cuta ta SARS-CoV-2, don haka mafi kyawun nuni na haɗarin gwajin inganci ga COVID-199, tunda takamaiman T. Kwayoyin iya hana kamuwa da cuta.ba tare da seroconversion10,11.Duk da haka, auna martanin ƙwayoyin T cell ya sami ƙasa da hankali saboda matsalolin hanyoyin da matsalolin dabaru wajen samun da jigilar samfuran jini, musamman lokacin gudanar da manyan nazarin binciken don tantance ingancin rigakafin da kuma lura da rigakafi.Koyaya, mutanen da aka yi wa alurar riga kafi suna nuna ƙarfin aikin ƙwayoyin T a kan bambance-bambancen SARS-CoV-2, mai yuwuwar rage asarar sake kunnawar rigakafi don iyakance tsananin COVID-1912,13.
Anan, mun nemi fahimtar ko ma'auni guda na amsawar kwayar halitta ta SARS-CoV-2 na iya yin hasashen cikakken haɗarin kamuwa da cutar SARS-CoV-2 a cikin watanni 6 na samfurin jini, ba tare da la'akari da abubuwan da ke haifar da rigakafin rigakafi ba.Domin yin gwajin kwayar halitta mai girma na T cell kuma ya dace da babban karatu, mun kuma yi ƙoƙarin sanya gwajin a ɗan ƙaranci don a iya yin ta ta amfani da samfurin jini na ɗan yatsa.
Mun auna martanin rigakafi na salon salula da na ban dariya a cikin masu ba da gudummawa masu lafiya ta amfani da haɗin gano ƙwayoyin SARS-CoV-2 T da ƙwayoyin rigakafi na IgG dangane da dukkanin jini mai jiwuwa (don halayen mahalarta, duba Maris 2022 14. A cikin masu ba da rigakafin alurar riga kafi, SARS-CoV-2- An ƙaddara takamaiman martanin T-cellular ta hanyar auna matakan plasma interferon-γ (IFN-γ) biyo bayan haɓakar jini gaba ɗaya tare da peptide SARS-CoV-2 (kamar yadda a baya, refs. 14,15,16,17,18) da kuma martanin IgG da ke da alaƙa. tare da nucleocapsid (N) sun karu a cikin wadanda suka ba da rahoton kamuwa da cuta a baya, ko da yake dukkanin amsa sun kasance mafi girma a cikin masu ba da gudummawar da ba a riga sun kamu da su ba, mafi girma a cikin jiki (Fig. 1a,b) Amsoshi na IgG akan spike glycoproteins (RBD, S1, S2) sun kasance mafi girma a cikin masu ba da gudummawar allurar riga-kafi (Hoto 1c-e).
An auna martanin SARS-CoV-2 takamaiman IFN-γ+ T ta hanyar gwajin jini gaba ɗaya kuma dangane da allurar rigakafin mahalarta da kuma yanayin kamuwa da SARS-CoV-2 na farko (wanda PCR da / ko gwajin kwarara na gefe ya tabbatar)'Vac + /Inf +'n = 60 (kore), 'Vac + /Inf-' n = 82 (blue), 'Vac-/Inf +' n = 4 (rawaya), 'Vac-/Inf-' n = 1 (ba a yi amfani ba).SARS-CoV-2-takamaiman halayen IgG masu ɗaurin kai suna niyya nucleocapsid (“N”) (b; **** P <0.0001, ** P = 0.0016), yanki mai ɗaure mai karɓa (“RBD”) (c; ** P = 0.0022, * P <0.015), spike subunit 1 ("S1") (d; *** P = 0.0005, * (Vac + / Inf + vs. Vac + / Inf-) P = 0.022, * (Vac- /Inf+ vs. Vac+/Inf-) P = 0.012) da kuma kololuwa subunit 2 ("S2") (e) an auna ta ta venous dukan jini gwaje-gwaje da kuma dangane da mahalarta alurar riga kafi da kuma kafin SARS -CoV-2 (tabbatar da PCR da/ ko gwajin kwarara na gefe) yanayin kamuwa da cuta.'Vac + /Inf +' n = 60 (kore), 'Vac + /Inf-' n = 71-82 (blue), 'Vac-/Inf +' n = 4 (rawaya).An yi kwatancen ta amfani da gwajin Kruskal-Wallis, wanda aka daidaita don kwatancen da yawa ta amfani da gwajin Dunn.Ana nuna bayanan azaman ginshiƙi (layi na tsakiya a tsaka-tsaki, iyakar babba a kashi 75th, ƙaramin iyaka a kashi 25) tare da wasiƙa a mafi ƙaranci da ƙimar ƙima.Kowace digo tana wakiltar mai bayarwa.Ana ba da albarkatun ɗanyen bayanai a cikin nau'in fayilolin ɗanyen bayanai.
Bayan samfurin jini, an tambayi mahalarta don su ba da rahoton kansu tabbatacce PCR da/ko sakamakon gwajin kwarara na gefe don COVID-19;Idan mahalarta sun gwada inganci tsakanin 1 Satumba 2021 da 29 Disamba 2021, ana tsammanin sun kamu da cutar ta Delta (B.1.617.2) bambance-bambancen coronavirus da Omicron (B.1.1.529) zuwa Kiwon Lafiyar Jama'a Wales bayan 29 ga Disamba, 2021, lokacin da wannan zaɓi na damuwa ya zama rinjaye.Daga cikin masu ba da gudummawa 148 masu kimantawa, mun lura da adadin kamuwa da cuta na 26.3% (39/148) a cikin watanni 6 na gudummawar jini, 38 daga cikinsu sun sami kashi na biyu ko na uku na rigakafin COVID-19 (ciwon kamuwa da cuta ya faru ne bayan Pfizer/BioNTech) BNT162b2) rigakafin mRNA ko maganin AstraZeneca (ChAdOx1 nCoV-19));wani mai bayar da alluran rigakafi shima ya kamu da cutar.Girman martanin SARS-CoV-2-takamaiman IFN-γ-tabbatacce T cell ya ragu sosai a cikin waɗanda suka ba da rahoton ingantaccen gwajin gwaji don COVID-19 fiye da masu ba da gudummawa marasa kamuwa (P <0.0001; siffa 2a), galibi saboda mafi kyawun shigar da martanin cell T ta hanyar rigakafi a wasu mahalarta (P = 0.050; Ƙarin Hoto 1).Babu wata alaƙa tsakanin girman amsawar tantanin halitta IFN-γ+ T da lokacin zuwa ingantaccen sakamakon gwajin COVID-19 (Ƙarin Hoto 2).Sabanin haka, ba RBD-, S1-, S2-dauri IgG martani (Figures 2b-d) ko RBD-, S1-neutralizing antibody martani kasance musamman ga daji-type ko delta SARS-CoV-2 (B.1.617).) (Ƙarin Hoto na 3) na iya bambanta tsakanin mutanen da ke cikin haɗarin kamuwa da cuta.Koyaya, ƙananan martanin IgG masu alaƙa da N-ƙira da SARS-CoV-2 sun danganta da haɗarin kamuwa da COVID-19 (P = 0.0084; Hoto 2e);waɗanda suka gwada inganci sun kasance 85% ƙasa da ƙasa (P = 0.00035; KO 0.15, 95).% CI: 0.047-0.39 (Ƙarin Hoto 4).
Samfuran jini na jini daga masu ba da gudummawa lafiya (n = 148) sun tantance takamaiman martanin SARS-CoV-2-IFN-γ+ T-cell (a; **** P <0.0001) da ɗaure mai karɓar Spike ga takamaiman SARS-CoV -2 abin kara kuzari.yanki ("RBD") (b), spike 1 subunit ("S1″) (c), spike 2 subunit ("S2″) (d), da nucleocapsid ("N") (e; ** P = 0.0084) .Mahalarta da suka gwada inganci don COVID-19 (PCR da/ko kwarara ta gefe) sun gano;duk cututtuka sun faru a cikin watanni 6 na samfurin jini.An yi kwatancen ta amfani da gwajin Mann-Whitney mai wutsiya biyu.Ana nuna bayanan azaman ginshiƙi (layi na tsakiya a tsaka-tsaki, iyakar babba a kashi 75th, ƙaramin iyaka a kashi 25) tare da wasiƙa a mafi ƙaranci da ƙimar ƙima.Kowace digo tana wakiltar mai bayarwa.ns ba shi da mahimmanci.Taswirar zafi f tana nuna alaƙar matsayi na Spearman tsakanin masu canji don ƙayyadadden saitin bayanai.Kwatancen da ba su da mahimmancin ƙididdiga an cire su daga matrix kuma an yi musu alama da sel mara kyau.Ana ba da albarkatun ɗanyen bayanai a cikin nau'in fayilolin ɗanyen bayanai.
An yi la'akari da ingantaccen yankewar ganowar da aka saita na 14 a matsayin mai sabani don tantance haɗarin sake kamuwa da cuta, don haka an kafa jeri na tsaka-tsaki don kafa cikakkun sigogin haɗari.Tsarin ƙididdiga, wanda kawai ya haɗa da masu canji waɗanda ke da tasiri mai mahimmanci akan sakamakon, ya nuna cewa girman SARS-CoV-2-takamaiman amsa tantanin halitta IFN-γ+ T shine mafi mahimmancin rigakafin ƙwayoyin cuta don tantance damar mutum na kasancewa. gwajin COVID.-19 tabbatacce (Hoto na 2f da Ƙarin Hoto 4).Marasa lafiya da SARS-CoV-2 takamaiman amsa tantanin halitta IFN-γ+ T a cikin na uku (194-489 pg/ml IFN-γ) da na huɗu (> 489 pg/ml IFN-γ) quartiles 65% (P = 0.055; KO 0.35, 95% CI: 0.11-1.00) da 90% (P = 0.0050; KO 0.098, 95% CI: 0.014-0.42) sun sami ƙarin mahalarta.Damar ba su da yawa (Ƙarin Hoto 4).Gabaɗaya, mahalarta tare da takamaiman martanin cell na SARS-CoV-2 daga jini mai jiwuwa ≤79 pg/mL IFN-γ suna da haɗarin 43.2% na kamuwa da cuta a cikin watanni 6, idan aka kwatanta da amsa>489 pg/ml.ml na IFN-γ yana da haɗarin kamuwa da cuta na 5.4% (tebur 2).
Gwajin jini gabaɗaya na Venous yana da iyaka a iyawarsa saboda buƙatar tattara samfurin ta phlebotomist.Don haɓaka samuwar ƙwayoyin T da gwajin IgG don SARS-CoV-2, an ƙirƙiri madadin gwajin jini na capillary don bawa mahalarta damar samun samfuran jinin yatsa a gida.A iyakar saninmu, ba a sami rahotannin baya ba game da auna aikin tantanin halitta na antigen a cikin samfuran jini na capillary.An nuna alaƙa mai ƙarfi a baya tsakanin kididdigar lymphocyte da aka samu ta amfani da kwatankwacin samfuran jini da venous jini.Bugu da kari, an ba da rahoton cewa duk binciken da aka yi na tushen jini da ke auna martanin tantanin halitta na SARS-CoV-2 yana amfani da 320 μL na jini mai jijiya kawai, 20 yana kawar da damuwa game da yawan sel T a cikin samfuran jinin capillary.
Mun yi amfani da wannan babban madaidaicin daidaitaccen ƙimar haɗin gwiwar sel na SARS-CoV-2 T da ƙwayoyin rigakafi na IgG dangane da dukkanin jini don auna amsawar salon salula da na ban dariya a cikin mahalarta masu kamuwa da cuta daban-daban da matsayin riga-kafi / kamuwa da cuta (Table 1).dauka daga ko'ina cikin Birtaniya tsakanin 24 Janairu da 14 Maris 202214. Yawancin (90.9%) na samfurin yatsa an samu daidai kuma an aika zuwa dakin gwaje-gwaje a cikin sa'o'i 24 na tarin.A wasu lokuta, ana karɓar samfurori a cikin sa'o'i 48 na zana jini, amma babu ɗayan waɗannan samfuran da ya wuce gwajin ingancin inganci kuma bai shafi ma'aunin T cell gabaɗaya ba (Ƙarin Hoto 5).Kodayake akwai bambance-bambance a cikin girman amsawar tantanin halitta na SARS-CoV-2-takamaiman IFN-γ+ T da aka auna a cikin samfuran jini na jini da venous a wasu mutane, babu wani bambance-bambance masu mahimmanci gabaɗaya (P = 0.88; Ƙarin Hoto 6). ).).
SARS-CoV-2-takamaiman martanin cell IFN-γ+ T sun karu sosai a cikin mutanen da aka yi wa alurar riga kafi waɗanda kuma suka ba da rahoton kamuwa da cuta a baya (P = 0.0001), amma bai fi girma ba fiye da na masu ba da gudummawar da ba a yi musu allurar a baya ba (P = 0.19, Fig. 3 a).).Amsoshin IgG game da spike glycoprotein (RBD, S1, S2) sun kasance mafi girma a cikin masu ba da gudummawar alurar riga kafi fiye da masu ba da rigakafi, ba tare da la'akari da matsayin kamuwa da cuta ba (Hoto 3b-d).Abin sha'awa, ma'anar amsawar N-daure IgG ta kasance mafi girma a cikin mahalarta waɗanda ba a yi musu allurar riga-kafi ba idan aka kwatanta da waɗanda aka yi wa allurar, kodayake wannan bai kai ga mahimmanci ba (Hoto 3e).Daga cikin masu ba da agaji marasa rigakafi da marasa lafiya waɗanda suka bayyana kansu, 15 na 37 (40.5%) mahalarta sun kasance tabbatacce ga N-linked IgG, sama da matakin da aka kafa a baya na 2.0 BAU/mL14;waɗannan mahalarta 15 Goma sha biyu daga cikin waɗannan marasa lafiya sun gwada tabbatacce don amsawar kwayar halitta ta IFN-γ+ a sama da matakin da aka kafa a baya na 22.7 pg/mL IFN-γ14.Don haka, da alama waɗannan mahalarta sun kamu da cutar ta SARS-CoV-2 a baya kuma ba a gwada su don COVID-19 ba saboda zaɓi na sirri, rashin PCR da / ko kayan aikin kwarara na gefe, ko kuma asymptomatic.Kodayake akwai mahimmin alaƙa tsakanin martanin T cell zuwa IFN-γ+ da matakan IgG masu alaƙa da N-linked a cikin masu ba da gudummawar da ba a ba da rigakafin ba (P = 0.0044; Ƙarin Hoto, N-linked IgG amsa ya ragu da sauri fiye da amsawar IgG na N-linked, yayin da IFN-γ + T cell martani an kiyaye ba tare da la'akari da matsayin rigakafin, kodayake adadin masu ba da gudummawa a makonni 50 bayan ƙalubalen ya yi ƙasa (Ƙarin Hoto. 8).Nau'in rigakafin gabaɗaya ya ɗan bambanta a cikin martanin IgG da aka lura musamman ga SARS-CoV-2, T. Kwayoyin da ke da alaƙa da RBD, kodayake mahalarta waɗanda suka karɓi allurai biyu na BNT162b2 waɗanda suka biyo bayan maganin mRNA1273 sun nuna matakan IFN-γ + T da yawa sun fi kulawa da SARS-CoV-2 fiye da waɗanda suka karɓi allurai biyu na ChAdOx1 da BNT162b2 (Ƙari). Hoto 9) Bugu da ƙari, rahotannin da aka ba da rahoton ba su da bambanci sosai a cikin amsawar T cell da aka lura da su idan aka kwatanta da masu ba da lafiya (Ƙarin Hoton 10).
An auna martanin SARS-CoV-2 takamaiman IFN-γ+ T ta hanyar gwajin jini gaba ɗaya kuma an dogara ne akan allurar rigakafin mahalarta da kuma yanayin kamuwa da SARS-CoV-2 na farko (tabbatar ta PCR da/ko gwajin kwarara ta gefe).'Vac + /Inf +' n = 42 (kore), 'Vac + /Inf-' n = 158 (blue), 'Vac-/Inf +' n = 33 (rawaya), 'Vac- / Inf-' n = 37 (launin toka).****P <0.0001, ***P = 0.0001, *(Vac +/Inf- vs. Vac-/Inf-) P = 0.045, *(Vac-/Inf + vs. Vac- / Inf-) P = 0.014 .SARS-CoV-2 ƙayyadaddun halayen IgG na ɗaurin kai ga yanki mai ɗaure mai karɓar karu (“RBD”) (b; **** P <0.0001, ns: ba mahimmanci), ƙarar subunit 1 (“S1”) (c; * * ** P <0.0001, ns: ba mahimmanci), spike subunit 2 ("S2″) (d; **** P <0.0001, *** P = 0.0005, * P = 0.016) da nucleocapsid ("N") (e; **** P <0.0001, ns ba mahimmanci) an auna su ta amfani da cikakken nazarin jini na venous kuma dangane da allurar rigakafin mahalarta da kuma kafin SARS-CoV-2 (tabbatar da PCR da / ko bincike na kwarara ta gefe) An rarraba cututtuka ta hanyar. matsayi.'Vac + /Inf +' n = 46 (kore), 'Vac + /Inf-' n = 182 (blue), 'Vac-/Inf +' n = 34 (rawaya), 'Vac-/Inf-' n = 37 (launin toka).An yi kwatancen ta amfani da gwajin Kruskal-Wallis, wanda aka daidaita don kwatancen da yawa ta amfani da gwajin Dunn.Ana nuna bayanan azaman ginshiƙi (layi na tsakiya a tsaka-tsaki, iyakar babba a kashi 75th, ƙaramin iyaka a kashi 25) tare da wasiƙa a mafi ƙaranci da ƙimar ƙima.Kowace digo tana wakiltar mai bayarwa.Ana ba da albarkatun ɗanyen bayanai a cikin nau'in fayilolin ɗanyen bayanai.
Kamar yadda ya gabata, an nemi mahalarta su bayar da rahoton tabbataccen sakamakon PCR da/ko na gefe don COVID-19;a cewar Hukumar Lafiya ta Burtaniya, ana tsammanin mahalarta sun kamu da cutar ta Omicron coronavirus (B.1.1.529) a lokacin gwajin bambance-bambancen kwayar cutar, saboda ita ce bambance-bambancen da ke cikin Burtaniya yayin lokacin binciken.Daga cikin masu ba da gudummawa 299 masu ƙima, mun lura da adadin kamuwa da cuta na 8.0% (24/299) a cikin watanni uku na gudummawar capillary, bakwai daga cikinsu ba a yi musu allurar ba.Adadin cututtuka tsakanin duk mahalarta ya kasance ƙasa da waɗanda suka gwada inganci don COVID-19 (10.7%) fiye da waɗanda suka gwada rashin lafiyar COVID-19 (24.4%, Table 1), wanda na iya kasancewa saboda gaskiyar cewa mahalarta tare da wasu cututtuka sun fi taka tsantsan kuma suna kariya daga abubuwan da za su iya haifar da su kamar ciwon sukari da ciwon daji.Kamar yadda aka gani a cikin rukunin jini na venous, SARS-CoV-2-specific interferon-γ (IFN-γ) -tabbatattun ƙwayoyin T waɗanda aka auna a cikin samfuran jinin capillary daga daidaikun mutane da ke ba da rahoton ingantaccen gwajin gwaji na COVID-19.Girman amsawa ya kasance ƙasa da ƙasa fiye da masu ba da agaji marasa lafiya (P = 0.034; Hoto 4a) saboda ƙarancin ƙarancin shigar da amsawar kwayar cutar T ta hanyar rigakafi da / ko kamuwa da cuta ta gaba (Ƙarin Hoto 11).Hakazalika, ba RBD-, S1-, S2-dauri IgG martani (Figures 4b-d) ko RBD-, S1-neutralizing antibody martani kasance takamaiman ga daji-type ko delta SARS-CoV-2 (B. 1.617).(Ƙarin adadi na 12).Ana iya gano daidaikun mutane a kowane muhimmin haɗarin kamuwa da cuta.Ya bambanta da ƙungiyar venous, martanin IgG masu alaƙa da N suma ba su bambanta haɗarin COVID-19 (Hoto 4e), yana ba da shawarar cewa bambance-bambancen Omicron (B.1.1.529) yana ƙaruwa da gujewa rigakafi a cikin mutanen da suka kamu da cutar, kamar yadda aka bayyana kwanan nan 21. Sabanin haka, ƙarfin SARS-CoV-2-takamaiman amsa tantanin halitta IFN-γ T shine ya sake zama mafi mahimmancin canji a cikin ƙayyadaddun daidaitattun daidaiton gwaji ga COVID-19 (Hoto 4f).Gabaɗaya, mahalarta tare da takamaiman amsawar T-cell na SARS-CoV-2 ≤23.7 pg/mL IFN-γ suna da haɗarin kamuwa da cuta 14.9% a cikin watanni uku idan aka kwatanta da amsa>141.6 pg/ml.ml IFN.-γ yana da haɗarin kamuwa da cuta na 4.4% (Table 2).
IFN-γ+ T cell martani takamaiman ga SARS-CoV-2 (a; * P = 0.034) da SARS-CoV-2 takamaiman IgG-niyya mai ɗaure mai karɓa ("RBD") (b), juzu'in juzu'i 1 (' S1′) (c), karu subunit 2 ('S2′) (d) da nucleocapsid daurin dauki ('N') (e).Mahalarta sun gano suna da inganci don gwajin COVID-19 (PCR da/ko gwajin jini na gefe), duk cututtukan sun faru ne a cikin watanni 3 na samfurin jini.An yi kwatancen ta amfani da gwajin Mann-Whitney mai wutsiya biyu.Ana nuna bayanan azaman ginshiƙi (layi na tsakiya a tsaka-tsaki, iyakar babba a kashi 75th, ƙaramin iyaka a kashi 25) tare da wasiƙa a mafi ƙaranci da ƙimar ƙima.Kowace digo tana wakiltar mai bayarwa.ns ba shi da mahimmanci.Taswirar zafi f tana nuna alaƙar matsayi na Spearman tsakanin masu canji don ƙayyadadden saitin bayanai.Kwatancen da ba su da mahimmancin ƙididdiga an cire su daga matrix kuma an yi musu alama da sel mara kyau.Ana ba da albarkatun ɗanyen bayanai a cikin nau'in fayilolin ɗanyen bayanai.
Yayin da muka matsa zuwa mataki na gaba na cutar ta COVID-19, za a mai da hankali kan yin rigakafi zuwa ga gudanar da haɗarin mutum da gano membobin al'umma masu rauni.Ƙaddamar da alaƙar rigakafi ga COVID-19 yana da mahimmanci don ganowa da kuma kula da waɗannan ƙungiyoyi masu haɗari.Yanzu akwai ƙara shaida cewa rigakafin T-cell yana ba da kariya daga kamuwa da cutar SARS-CoV-2 kuma yana iyakance tsananin COVID-1910.Bayanan da aka gabatar anan sun nuna cewa haɗakar ƙarfin SARS-CoV-2-takamaiman martanin tantanin halitta IFN-γ+ T game da karu, membrane, da sunadarai na tsarin nucleocapsid suna ba da kariya mafi girma daga COVID-19 fiye da ɗaurin antibody.19 yana haɓaka ko kawar da martani. .kuma yakamata a yi la'akari da shi lokacin tantance rigakafin mutum da/ko garken garken.Kwayoyin cutar RNA irin su SARS-CoV-2 ko cutar mura A (IAV) suna guje wa kawar da kwayar cutar ta hanyar saurin haɓakar abubuwan da ke tattare da ƙwayoyin B-cell akan antigens na saman da ƙwayoyin rigakafi suka gane.Amsar kariya ta rigakafi da ƙwayoyin T ke bayarwa na iya yin nuni da niyya na epitopes daga ƙarin yankuna da aka kiyaye su na sunadaran ƙwayoyin cuta waɗanda ba za su iya tsere wa amsawar rigakafi da sauri ba.Kariyar T-cell daga sabon bambance-bambancen SARS-CoV-2 yayi kama da kariyar heterosubtypic wanda T cell ke yin niyya na sunadaran da aka adana da aka gani a cikin nau'ikan IAV22,23.
Duk da babban yuwuwar auna martanin garkuwar salula ga COVID-19, an ba da kulawa kaɗan ga haɓaka ingantaccen, babban abin samarwa, daidaitaccen ƙididdigar T-cell.Matsalolin gargajiya da farashin da ke da alaƙa da auna martanin tantanin halitta T sun hana ingantacciyar ƙayyadaddun rigakafin T cell lokacin da ake tantance yawan rigakafi na yawan jama'a.Yayin da tallace-tallace da yawa na ƙididdigar haɓakar peptide na jini sun kasance kwanan nan, kowa a halin yanzu yana buƙatar phlebotomist don samun jini, iyakance samuwa da sikelin.Ana amfani da tsarin jinin capillary don tantance yawan ƙwayoyin rigakafi na SARS-CoV-2 a cikin yawan jama'a.Mun daidaita gwaje-gwajen jini na capillary don yin cikakken gwajin kuzarin peptide na jini don tantance amsawar kwayar halittar T zuwa sunadaran tsarin SARS-CoV-2 da takamaiman martanin rigakafin cutar SARS-CoV-2.A gaskiya ma, haɗakar ma'auni na musamman na SARS-CoV-2-takamaiman ƙwayoyin cuta da ƙwayoyin T a cikin samfurin jini guda ɗaya yana da kyau sosai: (i) yana rage buƙatar gwajin jini da yawa a kowane ɗan takara, (ii) inganta ƙwarewar mahalarta da fahimta;(iii) inganta dabaru da rage kwafi, (iv) rage tasirin muhalli kamar yadda ake buƙatar ƙarancin abubuwan amfani da dakin gwaje-gwaje da isar da samfur.Ko da yake gabaɗaya IFN-γ reactivity ya kasance daidai tsakanin madaidaicin venous da samfuran jini na capillary, an lura da shi ya kasance ƙasa da ƙasa a cikin ƙungiyar jini na mahalarta (Fig. 4a) idan aka kwatanta da ƙungiyar jini ta venous (Fig. 2a).Ƙimar IFN-γ Akwai bayanai da yawa don wannan binciken, wato, yawancin mahalarta tare da cututtuka da ke buƙatar maganin rigakafi da aka dauka a cikin ƙungiyar samfurin jini na capillary (Table 1) da Viability da / ko aiki na kwayoyin T da aka samu daga jijiyoyin jini. samfurori na iya zama ƙananan, musamman la'akari da yanayin ajiyar dogon lokaci na samfurori kafin haɓakar peptide.
Alurar riga kafi na COVID-19 da ake samu a halin yanzu yana ba da mafi kyawun kariya daga cututtuka masu tsanani ga yawancin masu karɓa a cikin watanni 6 na rigakafin8.Abin ƙarfafawa, duk da ƙarancin allurar rigakafin da aka haifar da serological bambance-bambancen SARS-CoV-26,7, martanin T-cell da aka samu ta hanyar allurar rigakafin SARS-CoV-2 na daji sun kasance suna mai da hankali sosai, yayin da wasu 25 suka fito.Bayanan da muke gabatarwa a nan suna nuna mahimmancin ƙima mai faɗi game da rigakafin rigakafin rigakafi, yana nuna alluran rigakafin rashin isasshen rigakafi na T-cell don hana kamuwa da cuta kwatsam da ci gaba da yaɗuwar ƙwayar cuta.Mun kuma lura cewa yawancin mutanen da ba a yi musu allurar rigakafi ba da aka ɗauka a cikin ƙungiyar ta capillary suna da muhimmiyar amsa ta musamman na ƙwayoyin T-Sars-CoV-2 (da N-binding IgG) ba tare da la'akari da rigakafin da aka yi a baya ba, wanda wataƙila saboda kamuwa da cuta a baya.Maimakon a yi wa mutanen da suka dace allurar rigakafi, ya kamata a tantance haɗarin kamuwa da su bisa la'akari da matsayinsu na rigakafi na yanzu da kuma zaɓin da aka yi.
Iyakoki na wannan binciken sun haɗa da tabbacin cewa mahalarta sun ba da rahoton kamuwa da cutar da kansu tare da SARS-CoV-2 bayan tattara jini don sanin mahimmancin rigakafi;wasu mahalarta na iya samun kamuwa da cutar asymptomatic kuma ba za su iya yin gwajin PCR da/ko gwajin kwarara ta gefe don COVID-19 ba.Saitin bayanan mu kuma ya rasa bayanai game da magungunan mahalarta a lokacin gwajin jini.Bugu da ƙari, da aka ba cewa duk mahalartanmu sun ba da rahoton kawai alamu masu laushi / matsakaici ko babu alamun, ba zai yiwu ba a gano martanin rigakafi daga saitin bayanan mu wanda ya annabta haɗarin haɗari mai tsanani da asibiti don COVID-19.Koyaya, kasancewar martanin sel CD8+ T akan takamaiman ƙayyadaddun abubuwan nucleocapsid kwanan nan an danganta su da kariya daga mummunan COVID-1926.Bugu da kari, kididdigar da aka yi amfani da ita a nan ba ta auna martanin kwayar cutar T ba ga takamaiman sunadaran da ba na tsarin SARS-CoV-2 waɗanda aka nuna kwanan nan sun fi son taruwa a cikin ma'aikatan kiwon lafiya waɗanda ke hulɗa da masu cutar.Dangane da wannan aikin, idan aka yi la'akari da yawaitar watsawar al'umma a lokacin daukar ma'aikata da kuma yuwuwar kamuwa da kamuwa da cutar a cikin jama'a, adadin takamaiman ƙwayoyin SARS-CoV-2 da aka samu a cikin gwaje-gwajenmu suma suna da ikon sharewa.cututtuka na subclinical a cikin rukunin mu.A ƙarshe, ba mu auna samar da interleukin 2 ta sel T ba saboda aikinmu na baya ya nuna rashin kyawun gano takamaiman martanin tantanin halitta na SARS-CoV-214, kodayake takamaiman martanin IL-2 na iya nuna kasancewar giciye-reactivity.Kwayoyin da ke da alaƙa da kariya daga kamuwa da cutar SARS-CoV-211.
A hade, waɗannan bayanan suna nuna mahimmancin buƙatu na dogon nazari na dogon lokaci wanda ya haɗa da takamaiman martanin cell na SARS-CoV-2 cikin matakan rigakafin yawan jama'a.Ana iya taimakawa waɗannan ƙoƙarin ta hanyar haɓaka sabon gwajin jini na capillary wanda ke auna martanin T-cell.
Aikin binciken ya ɗauki mahalarta daga Fabrairu 2021 zuwa Maris 2022. Ƙungiyar masu ba da gudummawar lafiya (n = 148) waɗanda suka ba da gudummawar samfuran jini na venous sun ƙunshi ma'aikatan jami'a da ɗaliban da ke shiga sabis na gwajin COVID-19 na Jami'ar Cardiff ko ma'aikata a makarantar firamare a cikin CardiffDuk mahalarta suna da lafiya kuma ba su bayar da rahoton shan duk wani magungunan rigakafi ba (duba Table 1 don halaye).Ƙungiyar mahalarta waɗanda suka ba da gudummawar samfuran jinin jini sun haɗa da duk masu ba da gudummawa na son rai (shekaru 18+) daga ko'ina cikin Burtaniya.Tsakanin Janairu 24 da Maris 14, 2022, mahalarta 342 sun shiga cikin binciken, wanda 299 suka gabatar da samfuran jini zuwa dakin gwaje-gwaje.Mahalarta da yawa sun kasance ba a yi musu alluran rigakafi ba da/ko sun ba da rahoton munanan cututtuka, gami da cututtuka na autoimmune da ciwon daji (duba Table 1 don halaye).Wannan binciken ya sami amincewar ɗa'a daga Newcastle da North Tyneside 2 Kwamitin Da'a na Bincike (ID IRAS: 294246) da Kwamitin Da'a na Cibiyar Nazarin Magunguna na Jami'ar Cardiff (SREC ref: SMREC 21/01).Duk mahalarta sun ba da izini a rubuce kafin haɗawa.Mahalarta ba su sami wani diyya don shiga wannan binciken ba.
An samo samfuran jinin jini ta hanyar venipuncture cikin 6 ko 10 ml lithium ko sodium heparin vacutainers (BD).An samo samfuran jinin capillary tare da lancet na yatsa sannan kuma an tattara su a cikin microcontainers na heparin (BD).Ana buƙatar mafi ƙarancin 400 µl na jini;duk wani samfurin ƙasa da wannan adadin za a ƙi.Wasu dalilai na ƙin yarda da samfurin sun haɗa da babban coagulation da / ko hemolysis da gazawar tattara jini mai danko don bincike (Ƙarin Hoton 5).An sami samfuran jini na capillary 299 don tantance martanin antibody, wanda samfuran 270 kuma ana samun su don tantance martanin T cell.
SARS-CoV-2 takamaiman martanin cell T an tantance su ta amfani da COVID-19 Immuno-T assay (ImmunoServ Ltd) kuma an yi shi kamar yadda aka bayyana a baya14.A taƙaice, an ɗauki venous vacutainer 6 ml ko 10 ml sodium heparin (BD) daga kowane ɗan takara kuma an sarrafa shi a cikin dakin gwaje-gwaje a cikin awanni 12 na tarin jini.Kodayake yawancin samfurori an sarrafa su cikin sa'o'i 24, 400-600 μl heparinized microbleeding (BD) jinin capillary an tattara shi a cikin sa'o'i 48 na samfurin yatsa.Samfuran jini na jini da / ko na capillary an motsa su tare da wuraren tafkunan peptide daban na musamman don SARS-CoV-2 (bambance-bambancen nau'in daji) kamar yadda aka bayyana a baya14.Wannan ɗakin karatu na peptide ya ƙunshi jerin 420 15-mer tare da nau'ikan amino acid 11 da suka mamaye dukkan furotin (S1 da S2) (S; furotin NCBI: QHD43416 1), nucleocapsid phosphoprotein (NP; furotin NCBI: QHD43423 2) da membrane glycoprotein ; NCBI sunadaran: QHD43419 1) jerin coding (wanda ake kira "S-/NP-/M-combinatorial peptide library").Dukkan peptides an tsarkake su zuwa> 70%, an narkar da su a cikin ruwa maras kyau kuma an yi amfani da su a matakin ƙarshe na 0.5 μg / ml da peptide.An sanya samfurin a zazzabi na 37 ° C na awanni 20-24.Daga nan an saka bututun a 5000 × g na mintuna 3 kuma an tattara ~ 150 µl na plasma daga saman kowane samfurin jini.Ajiye samfuran plasma a -20 ° C har zuwa wata ɗaya kafin gudanar da gwajin gano cytokine/antibody.
An auna IFN-γ ta amfani da IFN-γ ELISA MAX Deluxe Set (BioLegend, lambar kasida 430116) kuma an yi shi bisa ga umarnin masana'anta.Nan da nan bayan an ƙara bayani tasha (2N H2SO4), an karanta microplate a 450 nm ta amfani da BioLegend Mini ELISA farantin.IFN-γ an ƙididdige shi ta daidaitaccen madaidaicin lanƙwasa ta amfani da GraphPad Prism.An ƙididdige ƙimar da ke ƙasa da ƙarancin ganowa na assay azaman 7.8 pg/ml, ƙimar sama da ƙimar ganowa na sama an rubuta su azaman 1000 pg/ml.
Anti-SARS-CoV-2 RBD/S1/S2/N IgG antibodies an auna ta ta amfani da Bio-Plex Pro Human IgG SARS-CoV-2 4-plex panel (Bio-Rad, cat. no. 12014634) da kuma lakafta bisa ga umarnin masana'anta .umarnin .Samfurori masu ba da rahoto sama da iyakar ƙididdigewa an sake nazarin su a dilution 1:1000.An auna matsakaicin ƙarfin haske na beads akan kayan aikin Bio-Plex 200 (Bio-Rad).VIROTROL SARS-CoV-2 an ƙididdige yawan abubuwan rigakafin ƙwayoyin cuta ta hanyar gwajin sarrafawa guda ɗaya (Bio-Rad) kuma an canza su zuwa WHO/NIBSC 20/136 Standard Reference Standard Units (BAU/ml) ta amfani da ma'aunin daidaitawar masana'anta.
RBD da S1 subunit-takamaiman ƙwayoyin rigakafin ƙwayoyin cuta da nau'in SARS-CoV-2 da nau'in daji da delta (B.1.617) SARS-CoV-2 an auna su ta amfani da Bio-Plex Pro Human SARS-CoV-2 Variant Neutralization Antibody Kit (Bio) -Rad, sashi na 12016897), bisa ga umarnin masana'anta.Auna matsakaicin ƙarfin kyalli akan Bio-Plex 200 (Bio-Rad) kuma ƙididdige hanawa kashi (watau neutralization) ta amfani da dabara mai zuwa:
An yi gwajin rigakafin kamuwa da cuta don SARS-CoV-2 kamar yadda aka bayyana a baya28.A taƙaice, 600 PFU na nau'in SARS-CoV-2 na daji an haɗa su tare da dilutions na plasma sau 3 a cikin kwafi na awa 1 a 37 ° C.Bayan haka an ƙara cakuda zuwa ƙwayoyin VeroE6 na awanni 48.Monolayers an gyara su tare da 4% paraformaldehyde, permeabilized tare da 0.5% NP-40 kuma an sanya shi na sa'a 1 a cikin toshe buffer (PBS mai ɗauke da 0.1% tsakanin 0.1% da 3% skimmed madara).Maganin rigakafi na farko (anti-nucleocapsid 1C7, Stratech) an ƙara shi zuwa toshe buffer na awa 1 a zafin jiki.Bayan wankewa, an ƙara maganin rigakafi na biyu (anti-mouse IgG-HRP, Pierce) zuwa toshe buffer na awa 1.An wanke masu monolayers, an haɓaka su ta amfani da Sigmafast OPD kuma an karanta su akan mai karanta farantin Clariostar Omega.Rijiyoyin da ba su da ƙwayar cuta, ba tare da ƙwayar cuta ba amma ba tare da ƙwayoyin rigakafi ba, da kuma daidaitaccen sera da ke nuna matsakaicin aiki an haɗa su cikin kowane gwaji azaman sarrafawa.
An gudanar da nazarin ƙididdiga a cikin GraphPad Prism (sigar 9.4.1).An gwada daidaitattun saitin bayanan ta amfani da gwajin Shapiro-Wilk.An yi amfani da ƙa'idodin da ba daidai ba don duk kwatancen.An yi amfani da gwajin Mann-Whitney don samfuran da ba a haɗa su ba.Duk gwaje-gwajen sun kasance masu gefe biyu tare da maƙasudin mahimmanci na P ≤ 0.05.
An yi nazarin binciken farko na saitin bayanai a cikin R (Sigar 4.0.3).Wannan ya haɗa da haɓaka matrix ɗin daidaitawa na univariate na Spearman, inda alaƙar tsakanin masu canji biyu ke wakilta ta girman da launi na murabba'ai.An ƙididdige mahimmancin ƙididdiga tsakanin ƙungiyoyi ta amfani da Spearman's rho, inda aka ɗauki ƙimar ≤0.05 mahimmanci.Kwatancen da ba su da mahimmancin ƙididdiga an cire su daga matrix kuma an yi musu alama da sel mara kyau.P-darajar an daidaita su don kwatancen da yawa ta amfani da gyaran Holm.An yi amfani da samfurin juzu'i na binary don daidaita tasirin masu canji a cikin bayanan akan ingantaccen amsa ga COVID-19.Amsoshin tantanin halitta na IFN-γ da ƙimar anti-RBD/S1/S2/N IgG titer an canza su zuwa dalilai, inda aka sanya kowane mutum zuwa adadin da ya dace don kowane maki.Bayan haka, an ƙaddamar da samfurin bincike na farko ta amfani da aikin glm a cikin kunshin ƙididdiga (V4.0.3).Matsakaicin rashin daidaituwa da aka samo daga wannan ƙirar ta asali an fitar da su daga ƙididdiga na ƙirar ta amfani da aikin 'odds_plot' a cikin kunshin OddsPlotty (V1.0.2).Lokacin haɓaka ƙirar tabbatarwa ta giciye, mun yi amfani da aikin "bestglm" daga fakitin bestglm (V0.37.3) don iyakance ra'ayin mai amfani da kuma tabbatar da cewa za'a iya zaɓar mafi kyawun tsarin tsinkaya.Hanyar da aka zaɓa ta kasance "m" kuma ma'aunin bayanin da aka yi amfani da shi don tantance dacewa samfurin shine AIC.An yi amfani da aikin guda ɗaya da aka kwatanta a sama don samun rabon rashin daidaituwa.
Don ƙarin bayani kan ƙirar binciken, duba ƙayyadaddun binciken Nature mai alaƙa da wannan labarin.
Ya kamata a tura wasiku da buƙatun kayan zuwa Dr. Martin Scarr ko Farfesa Andrew Godkin.Wannan labarin yana ba da bayanan asali.
Lambar R da aka yi amfani da ita don ƙirƙirar ƙididdiga yana samuwa a bainar jama'a ba tare da buƙata29 ba.Ana iya samun bayanan sake bugawa da lasisi a www.nature.com/reprints.
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