347 zitsulo zosapanga dzimbiri za mankhwala Kukula kwa magazi a venous kapena capillary, enieni a SARS-CoV-2, mayankho a T-cell amatsimikizira chitetezo ku COVID-19.

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347 zitsulo zosapanga dzimbiri za mankhwala

Chitsulo Chosapanga 347 Coil Tube Chemical Mapangidwe

Zomwe zimapangidwira komanso makina a chubu chachitsulo chosapanga dzimbiri 347 ndi motere:
- Carbon - 0.030% max
Chromium - 17-19%
Nickel - 8-10.5%
Manganese - 1% max

Zitsulo Zopanda 347 Coil Tube Mechanical Properties

Malinga ndi Stainless Steel 347 Coil Tube Manufacturer, Mechanical Properties of 347 Coil Tube:
- Kulimbitsa Mphamvu (psi) - 75,000 min
- Mphamvu Zokolola (psi) - 30,000 min
- Kutalikira (% mu 2 ″) - 25% min
Kuuma kwa Brinell (BHN) - 170 max

Kugwiritsa Ntchito ndi Kugwiritsa Ntchito Stainless Steel 347 Coil Tube

• Stainless Steel 347 Coil Tube yomwe imagwiritsidwa ntchito mu Magayo a Shuga.
• Chubu Chachitsulo chosapanga dzimbiri 347 chogwiritsidwa ntchito mu Feteleza.
• Coil Tube ya Stainless 347 yomwe imagwiritsidwa ntchito pamakampani.
• Coil Tube ya Stainless Steel 347 yomwe imagwiritsidwa ntchito muzomera zamagetsi.
• Chitsulo Chosapanga 347 Coil Tube chomwe chimagwiritsidwa ntchito mu Chakudya ndi Mkaka.
• Chitsulo chosapanga dzimbiri 347 Coil Tube chomwe chimagwiritsidwa ntchito popanga Mafuta ndi Gasi.
• Stainless Steel 347 Coil Tube Manufacturer omwe amagwiritsidwa ntchito mu ShipBuilding Industry.

Ma cell a SARS-CoV-2-enieni a T amaganiziridwa kuti amateteza ku matenda ndi kufalikira kwa COVID-19, koma palibe umboni wachindunji wa izi.Apa, tidayerekeza kuyeza kwamagazi athunthu a SARS-CoV-2-specific interferon-γ ma cell a T omwe ali ndi zotsatira zoyezetsa zoyezetsa za COVID-19 (PCR ndi/kapena kutuluka kwapambuyo) mkati mwa miyezi 6 ya kusonkhanitsa magazi a Lian.Mwa omwe adatenga nawo gawo 148 omwe adapereka zitsanzo zamagazi a venous, kukula kwa SARS-CoV-2-specific T cell kuyankha kunali kokulirapo mwa iwo omwe adatetezedwa kuposa omwe adadwala (P <0.0001).% chiwopsezo chotenga matenda, pomwe kukwera kwakukulu kunachepetsa ngoziyi kufika pa 5.4%.Zotsatirazi zidapangidwanso kwa owonjezera a 299 omwe adayesa kuyesa kwa magazi kwa scalable capillary komwe kungathandize kupeza chidziwitso cha chitetezo cha T-cell (14.9% vs. 4.4%).Chifukwa chake, kuyeza kwa ma T cell a SARS-CoV-2 kumatha kulosera za kuopsa kwa matenda ndipo kuyenera kuwunikiridwa poyang'anira momwe chitetezo cha mthupi chikuyendera.
Kuyeza ndikumvetsetsa kuyankha kwa chitetezo chamthupi ku matenda a SARS-CoV-2 ndikofunikira kupanga njira zamtsogolo zochepetsera thanzi la anthu komanso mavuto azachuma pakubuka kwamtsogolo kwa COVID-19.Kuzindikiridwa kwa chitetezo chamthupi kumapereka chidziwitso chofunikira chokhudza kutengeka kwa anthu ku matenda a virus, mwina chenjezo lachiwopsezo chogonekedwa m'chipatala, komanso kulola anthu kudziwongolera okha kuti atenge kachilomboka komanso chiopsezo chopatsa ena.Kuyang'anira chitetezo chamthupi kwatsimikizira kufunikira kowunika mphamvu ya katemera wa COVID-19 mwa odwala athanzi komanso omwe ali pachiwopsezo chachikulu1,2,3 makamaka omwe ali ndi matenda a SARS-CoV-24, ndipo kuzindikirika kwa chitetezo chamthupi kudzatanthauza kufunikira kolimbikitsa chitetezo chamthupi Pezani katemera ndikupewa. miliri yamtsogolo .
Kutetezedwa kwa munthu ku matenda a SARS-CoV-2 kumadalira pazifukwa zingapo: kuchuluka kwa ma virus panthawi yomwe akhudzidwa, mitundu yosiyanasiyana ya ma virus, zaka, katemera wam'mbuyomu / matenda, comorbidities, mankhwala, ndipo koposa zonse, matenda odana ndi SARS-CoV. .2 kusinthika kwa chitetezo chamthupi kumachitika panthawi yomwe wakhudzidwa ndi kachilomboka5.Kuwunika momwe chitetezo cha mthupi chimayankhira ku matenda a SARS-CoV-2 ndi/kapena katemera wayang'ana kwambiri zoyeserera za serological zomwe zimayesa kupezeka kwa ma antibodies apadera a mapuloteni opangidwa (mwachitsanzo spike glycoprotein).Komabe, kupezeka kapena kusapezeka kwa ma antibodies pawokha sikumatsimikizira bwino momwe chitetezo cha mthupi chimayankhira, chifukwa mayankho amachepetsedwa pakapita nthawi6 komanso kusalowerera ndale kwa mitundu yosiyanasiyana ya SARS-CoV-2 pakuchira kapena katemera wa anthu omwe apatsidwa katemera kawiri Zofooka, zomwe zitha kupangitsa kuti pakhale vuto lalikulu. kuchuluka kwa matenda opambana 7.Zowonadi, kutetezedwa kuzizindikiro za COVID-19 zoyambitsidwa ndi mtundu wa Omicron (B.1.1.529) kudachepera pafupifupi 10% pambuyo pa miyezi 4-6 yokha ya katemera wa mRNA, ngakhale chitetezo ku matenda oopsa chinapitilira> 68% kwa miyezi 78.Kuyeza mayankho osinthika a ma cell a T, omwe amapereka chitetezo chanthawi yayitali ku matenda a virus, ndiye chizindikiro chabwino kwambiri chotengera matenda a SARS-CoV-2, chifukwa chake ndikuwonetsa bwino za chiopsezo choyezetsa COVID-199, popeza T. maselo amatha kuteteza matenda.popanda seroconversion10,11.Komabe, kuyeza kwa mayankho a T cell sikunapezeke chidwi chochepa chifukwa cha zovuta za njira komanso zovuta zogwirira ntchito pakupeza ndi kutumiza zitsanzo za magazi a venous, makamaka pochita maphunziro akuluakulu owonetsetsa kuti aone ngati katemera akugwira ntchito ndikuwunika chitetezo chokwanira.Komabe, anthu omwe ali ndi katemera amawonetsa zochitika zamphamvu zama cell a T motsutsana ndi mitundu ya SARS-CoV-2, zomwe zitha kuthetsa kutayika kwa ma antibody reactivity kuti achepetse kuuma kwa COVID-1912,13.
Apa, tidafuna kuti timvetsetse ngati kuyeza kumodzi kwa ma cell a SARS-CoV-2 T kumatha kulosera za chiwopsezo cha matenda a SARS-CoV-2 mkati mwa miyezi 6 yotengera magazi, mosasamala kanthu za zomwe zidayambitsa chitetezo chamthupi.Pofuna kupanga kuyesa kwa maselo a T kukhala okwera kwambiri komanso kumagwira ntchito ku maphunziro akuluakulu, tinayesanso kuyesa kuyesa pang'ono kuti athe kuchitidwa pogwiritsa ntchito magazi a capillary fingerstick.
Tidayeza mayankho a chitetezo cham'thupi ndi nthabwala mwa opereka athanzi pogwiritsa ntchito kuzindikira kophatikizana kwa ma SARS-CoV-2 T ndi ma antibodies a IgG kutengera magazi athunthu am'mitsempha (kwa mawonekedwe a otenga nawo mbali, onani Marichi 2022 14. Mwa opereka katemera, SARS-CoV-2- Mayankho enieni a T-cellular adatsimikiziridwa ndi kuyeza plasma interferon-γ (IFN-γ) kutsatira kukondoweza kwa magazi ndi SARS-CoV-2 peptide (monga poyamba, refs. 14,15,16,17,18) ndi mayankho a IgG ogwirizana ndi nucleocapsid (N) adawonjezeka mwa omwe adanena za matenda am'mbuyomu, ngakhale kuti mayankho onsewa anali apamwamba mwa opereka omwe sanatengedwe kale omwe anali ndi kachilomboka, maximal m'thupi (mkuyu 1a, b) Mayankho a IgG motsutsana ndi spike glycoproteins (RBD, S1, S2) anali apamwamba kwambiri mwa opereka katemera omwe anali ndi kachilombo kale (Chithunzi 1c-e).
Mayankho a ma cell a SARS-CoV-2-enieni a IFN-γ+ T adayezedwa ndi kuyezetsa magazi kwa venous komanso kutengera katemera wa omwe adatenga nawo gawo komanso momwe alili ndi kachilombo ka SARS-CoV-2 (kutsimikiziridwa ndi PCR ndi/kapena kuyezetsa magazi)' Vac + /Inf +' n = 60 (wobiriwira), 'Vac + /Inf-' n = 82 (buluu), 'Vac-/Inf +' n = 4 (yellow), 'Vac-/Inf-' n = 1 (osagwiritsidwa ntchito).SARS-CoV-2-specific IgG reactions chandamale nucleocapsid (“N”) (b; ****P <0.0001, **P = 0.0016), spiked receptor-binding domain (“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) ndi nsonga yayikulu 2 (“S2”) (e) idayezedwa ndi kuyezetsa magazi kwa venous ndikutengera katemera wa omwe adatengapo nawo komanso SARS -CoV-2 yam'mbuyomu (yotsimikiziridwa ndi PCR ndi/ kapena lateral flow test) matenda opatsirana.'Vac + /Inf +' n = 60 (wobiriwira), 'Vac + /Inf-' n = 71-82 (buluu), 'Vac-/Inf +' n = 4 (yellow).Kuyerekeza kunachitika pogwiritsa ntchito mayeso a Kruskal-Wallis, osinthidwa kuti afananize kangapo pogwiritsa ntchito mayeso a Dunn.Deta imawonetsedwa ngati ma chart (mzere wapakati pa wapakati, malire apamwamba pa 75th percentile, malire otsika pa 25th percentile) ndi ndevu pamlingo wocheperako komanso wapamwamba kwambiri.Dontho lililonse likuyimira wopereka.Zambiri zimaperekedwa m'mafayilo a data yaiwisi.
Pambuyo poyesa magazi, otenga nawo mbali adafunsidwa kuti adzinene okha kuti ali ndi vuto la PCR ndi/kapena zotsatira zoyezetsa za COVID-19;Ngati otenga nawo gawo adapezeka kuti ali ndi kachilombo pakati pa 1 Seputembala 2021 ndi 29 Disembala 2021, akuyembekezeka kuti ali ndi kachilombo ka Delta (B.1.617.2) ndi Omicron (B.1.1.529) kupita ku Public Health Wales pambuyo pa Disembala 29, 2021, pomwe njira iyi ya nkhawa imakhala yayikulu.Mwa opereka 148 oyenerera, tidawona kuchuluka kwa matenda a 26.3% (39/148) mkati mwa miyezi 6 yopereka magazi, 38 mwa iwo adalandira mlingo wachiwiri kapena wachitatu wa katemera wa COVID-19 (kupambana kwa matendawa kunachitika pambuyo pa Pfizer/BioNTech ( BNT162b2) katemera wa mRNA kapena katemera wa AstraZeneca (ChAdOx1 nCoV-19));wopereka wopanda katemera nayenso adadwala.Kukula kwa mayankho a SARS-CoV-2-enieni a IFN-γ-positive T cell anali otsika kwambiri mwa omwe adanenanso za kuyezetsa koyezetsa kwa COVID-19 kuposa omwe adapereka omwe alibe kachilombo (P <0.0001; mkuyu 2a), makamaka chifukwa cha kulowetsedwa koyenera kwa mayankho a T cell ndi katemera mwa otenga nawo mbali (P = 0.050; Supplementary Fig. 1).Panalibe kugwirizana pakati pa kukula kwa IFN-γ+ T cell kuyankha ndi nthawi yopeza zotsatira zabwino za COVID-19 (Chithunzi Chowonjezera 2).Mosiyana ndi izi, mayankho a RBD-, S1-, S2-binding IgG (Zithunzi 2b-d) kapena RBD-, S1-neutralizing antibody mayankho anali enieni amtundu wakutchire kapena delta SARS-CoV-2 (B.1.617).) (Supplementary Fig. 3) akhoza kusiyanitsa pakati pa anthu omwe ali pachiopsezo chotenga matenda.Komabe, mayankho otsika a N-olumikizidwa ndi IgG motsutsana ndi SARS-CoV-2 ogwirizana ndi chiopsezo chotenga kachilombo ka COVID-19 (P = 0.0084; Chithunzi 2e);omwe adapezeka kuti ali ndi kachilomboka anali ochepera 85% (P = 0.00035; OR 0.15, 95).% CI: 0.047-0.39 (Chithunzi Chowonjezera 4).
Zitsanzo zamagazi a venous kuchokera kwa opereka athanzi (n = 148) adayesa mayankho a SARS-CoV-2-enieni a IFN-γ+ T-cell (a; ****P <0.0001) ndikumanga kwa Spike receptor ku SARS-CoV yeniyeni -2 zolimbikitsa.domain (“RBD”) (b), spike 1 subunit (“S1″) (c), spike 2 subunit (“S2″) (d), ndi nucleocapsid (“N”) (e; **P = 0.0084) .Omwe adapezeka ndi COVID-19 (PCR ndi/kapena lateral flow) adadziwika;matenda onse adachitika mkati mwa miyezi 6 mutatenga magazi.Kuyerekeza kunachitika pogwiritsa ntchito mayeso a Mann-Whitney okhala ndi michira iwiri.Deta imawonetsedwa ngati ma chart (mzere wapakati pa wapakati, malire apamwamba pa 75th percentile, malire otsika pa 25th percentile) ndi ndevu pamlingo wocheperako komanso wapamwamba kwambiri.Dontho lililonse likuyimira wopereka.ns sizofunikira.Heatmap f ikuwonetsa kulumikizana kwaupangiri wa Spearman pakati pazosintha zamtundu womwe watchulidwa.Kufananitsa komwe sikunali kofunikira pakuwerengera sikunaphatikizidwe ku matrix ndikuyika ma cell opanda kanthu.Zambiri zimaperekedwa m'mafayilo a data yaiwisi.
Kuyesedwa koyezetsa kotsimikizika kwa 14 kunkaonedwa kuti ndikosavuta kwambiri kuti ayesenso kuopsa kotenganso kachilomboka, motero magawo a interquartile adakhazikitsidwa kuti akhazikitse magawo owopsa.Zowerengera, zomwe zimangophatikiza zosintha zomwe zidakhudza kwambiri zotsatira, zidawonetsa kuti kukula kwa SARS-CoV-2-specific IFN-γ+ T cell kuyankha kunali kofunikira kwambiri kwa chitetezo chamthupi pozindikira mwayi wamunthu kukhala. adayezetsa COVID.-19 zabwino (Chithunzi 2f ndi Supplementary Figure 4).Odwala omwe ali ndi SARS-CoV-2 yeniyeni ya IFN-γ+ T selo yachitatu (194-489 pg/ml IFN-γ) ndi yachinayi (>489 pg/ml IFN-γ) quartiles 65% (P = 0.055; OR 0.35, 95% CI: 0.11-1.00) ndi 90% (P = 0.0050; OR 0.098, 95% CI: 0.014-0.42) anali ndi ophunzira ambiri.Mwayi ndi wochepa (Supplementary Fig. 4).Ponseponse, otenga nawo mbali omwe anali ndi SARS-CoV-2 kuyankha kwa T cell kuchokera m'magazi a venous ≤79 pg/mL IFN-γ anali ndi chiopsezo cha 43.2% chotenga kachilombo pakadutsa miyezi 6, poyerekeza ndi yankho> 489 pg/mL.ml ya IFN-γ anali ndi chiopsezo chotenga matenda a 5.4% (tebulo 2).
Kuyezetsa magazi kwa venous kumakhala kochepa chifukwa cha kufunikira kotolera zitsanzo ndi phlebotomist.Kuti muwonjezere kupezeka kwa kuyezetsa kwa T cell ndi IgG kwa SARS-CoV-2, njira ina yotsatsira magazi ya capillary yapangidwa kuti ilole otenga nawo mbali kuti atenge magazi a chala kunyumba.Monga momwe tikudziwira, sipanakhalepo malipoti am'mbuyomu onena za kuyeza kwa antigen-specific T cell function mu zitsanzo za magazi a capillary.Kulumikizana kwakukulu kwawonetsedwa kale pakati pa ma lymphocyte omwe amapezeka pogwiritsa ntchito zitsanzo zamagazi a capillary ndi venous.Kuphatikiza apo, zanenedwa kuti zoyesa zonse zotengera magazi zoyezera mayankho a ma T cell a SARS-CoV-2 amangogwiritsa ntchito 320 μL yokha yamagazi a venous,20 kuchotsa nkhawa za kuchuluka kwa ma cell a progenitor T mu zitsanzo zamagazi a capillary.
Tidagwiritsa ntchito njira yolumikizirana yokhazikika iyi ya ma SARS-CoV-2 T ndi ma antibodies a IgG kutengera magazi athunthu a capillary kuyeza kuyankha kwa chitetezo chamthupi mwa otenga nawo mbali omwe ali ndi ma comorbidities osiyanasiyana komanso katemera / matenda am'mbuyomu (Table 1).adalembedwa kuchokera ku UK kudutsa pakati pa 24 January ndi 14 March 202214. Ambiri (90.9%) a zitsanzo zala adapezedwa molondola ndikutumizidwa ku labotale mkati mwa maola 24 atatolera.Nthawi zina, zitsanzo zinalandiridwa mkati mwa maola a 48 atatenga magazi, koma palibe zitsanzozi zomwe zinadutsa kuwongolera khalidwe ndipo sizinakhudze chiwerengero chonse cha T cell kapena antibody (Supplementary Fig. 5).Ngakhale panali kusiyana kwa kukula kwa SARS-CoV-2-specific IFN-γ+ T cell kuyankhidwa motsatira magazi a capillary ndi venous magazi mwa anthu ena, panalibe kusiyana kwakukulu ponseponse (P = 0.88; Supplementary Fig. 6) ).).
Mayankho a SARS-CoV-2-enieni a IFN-γ+ T adawonjezeka kwambiri mwa anthu omwe adalandira katemera omwe adanenanso za matenda am'mbuyomu (P = 0.0001), koma osakwera kwambiri kuposa omwe adapereka kale omwe adalandira katemera (P = 0.19, Fig. 3 a).).Mayankho a IgG motsutsana ndi spike glycoprotein (RBD, S1, S2) anali apamwamba kwambiri mwa opereka katemera kuposa omwe adapereka osatemera, mosasamala kanthu kuti anali ndi kachilombo koyambitsa matenda (Chithunzi 3b-d).Chochititsa chidwi n'chakuti, kuyankha kwa N-bound IgG kunali kwakukulu kwambiri mwa omwe anali asanatengedwe kale omwe anali ndi kachilomboka poyerekeza ndi omwe adalandira katemera, ngakhale kuti izi sizinafikire kufunikira (Chithunzi 3e).Pakati pa opereka omwe sanatengedwe komanso osakhudzidwa omwe adadziwonetsera okha, 15 a 37 (40.5%) omwe anali nawo anali abwino kwa N-linked IgG, pamwamba pa malo omwe adakhazikitsidwa kale a 2.0 BAU / mL14;Otsatirawa a 15 khumi ndi awiri mwa odwalawa adayesedwa kuti ali ndi vuto la IFN-γ + T cell kuyankha pamwamba pa 22.7 pg / mL IFN-γ14.Chifukwa chake, zikutheka kuti omwe adatenga nawo gawowa adadwalapo kale ndi SARS-CoV-2 ndipo sanayezedwe ku COVID-19 chifukwa cha kusankha kwawo, kusowa kwa PCR ndi / kapena zida zoyendera, kapena anali asymptomatic.Ngakhale panali kulumikizana kwakukulu pakati pa mayankho a ma T cell ku IFN-γ + ndi ma IgG olumikizidwa ndi N mu opereka osalandira katemera (P = 0.0044; Chithunzi chowonjezera, mayankho a IgG olumikizidwa ndi N adatsika mwachangu kuposa mayankho a IgG olumikizidwa ndi N, pomwe IFN-γ + Mayankho a T cell adasungidwa mosasamala kanthu za katemera, ngakhale kuti chiwerengero cha opereka chithandizo pa masabata a 50 pambuyo pa zovuta chinali chochepa (Supplementary Fig. 8) . maselo ndi RBD-ogwirizana, ngakhale ophunzira amene analandira Mlingo iwiri ya BNT162b2 kutsatiridwa ndi mRNA1273 revaccination anasonyeza kwambiri milingo apamwamba IFN-γ + T maselo anali tcheru SARS-CoV-2 kuposa amene analandira awiri Mlingo wa ChAdOx1 ndi BNT162b2 (Supplementary Chithunzi cha 9) Kuwonjezera apo, ma comorbidities omwe adanenedwa anali ndi kusiyana kochepa kwakukulu mu mayankho a T cell poyerekeza ndi opereka thanzi labwino (Supplementary Fig. 10).
Mayankho a SARS-CoV-2-enieni a IFN-γ+ T adayezedwa ndi kuyezetsa magazi kwa capillary ndipo adatengera katemera wa omwe adatenga nawo gawo komanso kachilombo ka SARS-CoV-2 kam'mbuyo (kutsimikiziridwa ndi PCR ndi/kapena kuyezetsa magazi).'Vac + /Inf +' n = 42 (wobiriwira), 'Vac + /Inf-' n = 158 (buluu), 'Vac-/Inf +' n = 33 (yellow), 'Vac- /Inf-' n = 37 (imvi).****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 yeniyeni ya IgG yomangiriza zomwe zimamangiriza spike receptor binding domain ("RBD") (b; ****P <0.0001, ns: sizofunikira), spike subunit 1 ("S1") (c; * * **P <0.0001, ns: osati yofunika), spike subunit 2 (“S2″) (d; ****P <0.0001, ***P = 0.0005, *P = 0.016) ndi nucleocapsid (“N”) (e; ****P <0.0001, ns osafunikira) adayezedwa pogwiritsa ntchito kusanthula kwamagazi athunthu komanso kutengera katemera wa omwe adatenga nawo gawo komanso SARS-CoV-2 yam'mbuyomu (yotsimikiziridwa ndi PCR ndi / kapena kusanthula kwakuyenda kotsatira) Matendawa adagawidwa ndi udindo.'Vac + /Inf +' n = 46 (wobiriwira), 'Vac + /Inf-' n = 182 (buluu), 'Vac-/Inf +' n = 34 (yellow), 'Vac-/Inf-' n = 37 (imvi).Kuyerekeza kunachitika pogwiritsa ntchito mayeso a Kruskal-Wallis, osinthidwa kuti afananize kangapo pogwiritsa ntchito mayeso a Dunn.Deta imawonetsedwa ngati ma chart (mzere wapakati pa wapakati, malire apamwamba pa 75th percentile, malire otsika pa 25th percentile) ndi ndevu pamlingo wocheperako komanso wapamwamba kwambiri.Dontho lililonse likuyimira wopereka.Zambiri zimaperekedwa m'mafayilo a data yaiwisi.
Monga kale, otenga nawo mbali adafunsidwa kuti afotokoze zabwino za PCR ndi / kapena zotsatira zakuyenda kwa magazi kwa COVID-19;malinga ndi UK Health Agency, omwe adatenga nawo mbali adaganiziridwa kuti adatenga kachilombo ka Omicron (B.1.1.529) panthawi yoyezetsa kusiyanasiyana kwa kachiromboka, popeza kunali kosiyana kwambiri ku UK panthawi yophunzira.Pakati pa opereka 299 oyenerera, tidawona kuchuluka kwa matenda a 8.0% (24/299) mkati mwa miyezi itatu yopereka capillary, asanu ndi awiri mwa omwe sanatewere.Chiwerengero cha comorbidities pakati pa onse omwe adatenga nawo gawo chinali chocheperako mwa omwe adapezeka kuti ali ndi COVID-19 (10.7%) kuposa omwe adapezeka kuti alibe COVID-19 (24.4%, Table 1), zomwe zitha kukhala chifukwa choti otenga nawo gawo ndi ena. matenda amakhala osamala komanso amateteza ku zotsatira zomwe zingachitike monga shuga ndi khansa.Monga tawonera m'gulu lamagazi a venous, ma SARS-CoV-2-specific interferon-γ (IFN-γ) -ma cell a T omwe amayezedwa m'magazi a capillary kuchokera kwa anthu omwe akuwonetsa kuti ali ndi vuto la COVID-19.Kuyankha kwakukulu kunali kochepa kwambiri kusiyana ndi opereka omwe sanatengeke (P = 0.034; Chithunzi 4a) chifukwa cha kuperewera kwapang'onopang'ono kwa kuyankha kwa T cell ndi katemera ndi / kapena matenda asanayambe (Supplementary Figure 11).Mofananamo, mayankho a RBD-, S1-, S2-binding IgG (Zithunzi 4b-d) kapena RBD-, S1-neutralizing antibody mayankho anali enieni amtundu wakuthengo kapena delta SARS-CoV-2 (B. 1.617).(Chithunzi chowonjezera 12).Anthu omwe ali pachiwopsezo chilichonse chotenga matenda amatha kudziwika.Mosiyana ndi gulu la venous, mayankho a IgG okhudzana ndi N samasiyanitsa chiwopsezo cha COVID-19 (Chithunzi 4e), kutanthauza kuti mtundu wa Omicron (B.1.1.529) umakulitsa chitetezo chamthupi mwa anthu omwe ali ndi kachilombo kale, monga tafotokozera posachedwa 21. Mosiyana ndi izi, mphamvu ya SARS-CoV-2-specific IFN-γ T cell kuyankha kunalinso kusinthika kofunikira kwambiri pozindikira kuti ali ndi vuto la COVID-19 (Chithunzi 4f).Ponseponse, omwe anali ndi SARS-CoV-2-specific capillary T-cell response ≤23.7 pg/mL IFN-γ anali ndi chiopsezo cha 14.9% chotenga matenda pa miyezi itatu poyerekeza ndi yankho> 141.6 pg/mL.ml IFN.-γ anali ndi chiopsezo cha matenda a 4.4% (Table 2).
Mayankho a IFN-γ+ T amtundu wa SARS-CoV-2 (a; *P = 0.034) ndi SARS-CoV-2 yeniyeni ya IgG-targeted receptor-binding domain (“RBD”) (b), spike subunit 1 (' S1′) (c), spike subunit 2 ('S2′) (d) ndi nucleocapsid binding reaction ('N') (e).Otenga nawo mbali adadziwika kuti ali ndi chiyembekezo choyezetsa COVID-19 (PCR ndi/kapena kuyezetsa magazi pambuyo pake), matenda onse adachitika mkati mwa miyezi itatu atatenga magazi.Kuyerekeza kunachitika pogwiritsa ntchito mayeso a Mann-Whitney okhala ndi michira iwiri.Deta imawonetsedwa ngati ma chart (mzere wapakati pa wapakati, malire apamwamba pa 75th percentile, malire otsika pa 25th percentile) ndi ndevu pamlingo wocheperako komanso wapamwamba kwambiri.Dontho lililonse likuyimira wopereka.ns sizofunikira.Heatmap f ikuwonetsa kulumikizana kwaupangiri wa Spearman pakati pazosintha zamtundu womwe watchulidwa.Kufananitsa komwe sikunali kofunikira pakuwerengera sikunaphatikizidwe ku matrix ndikuyika ma cell opanda kanthu.Zambiri zimaperekedwa m'mafayilo a data yaiwisi.
Pamene tikulowa mu gawo lotsatira la mliri wa COVID-19, chidwi chidzasintha kuchoka pachitetezo kupita ku kasamalidwe ka anthu omwe ali pachiwopsezo ndikuzindikira anthu omwe ali pachiwopsezo.Kukhazikitsa njira zodzitetezera ku COVID-19 ndikofunikira kuti tidziwe bwino ndikusamalira magulu omwe ali pachiwopsezo chachikulu.Tsopano pali umboni wochulukirapo woti chitetezo cha T-cell chimateteza ku matenda a SARS-CoV-2 ndikuchepetsa kuopsa kwa COVID-1910.Zomwe zafotokozedwa apa zikuwonetsa kuti mphamvu zophatikizika za ma SARS-CoV-2-enieni a IFN-γ+ T cell mayankho motsutsana ndi spike, membrane, ndi nucleocapsid structural proteins amapereka chitetezo chokulirapo ku COVID-19 kuposa momwe antibody binding.19 imalimbikitsa kapena kuchepetsa mayankho .ndipo ziyenera kuganiziridwa powunika chitetezo cha munthu ndi/kapena ng'ombe.Ma virus a RNA monga SARS-CoV-2 kapena virus influenza A (IAV) amapewa kusalowerera ndale kwa serological posintha mwachangu ma epitopes a B-cell pama antigen apamtunda odziwika ndi ma antibodies.Chitetezo cha chitetezo cha mthupi chomwe chimaperekedwa ndi maselo a T chikhoza kuwonetsa kulunjika kwa ma epitopes kuchokera kumadera otetezedwa kwambiri a mapuloteni a tizilombo omwe sangathe kuthawa mwamsanga chitetezo cha mthupi.Chitetezo cha T cell-mediated motsutsana ndi mitundu ya SARS-CoV-2 ndi yofanana ndi chitetezo cha heterosubtypic cholumikizidwa ndi ma cell a T omwe amaloza mapuloteni osungidwa omwe amawonedwa mu ma IAV22,23 subtypes.
Ngakhale pali kuthekera kwakukulu koyesa kuyankha kwa chitetezo chamthupi ku COVID-19, chidwi chochepa chaperekedwa pakupanga zoyesa zolondola, zapamwamba, zoyeserera za T-cell.Zovuta zachikhalidwe ndi ndalama zomwe zimayenderana ndi kuyeza mayankho a T cell zimalepheretsa kutsimikizika kolondola kwa chitetezo cha T cell pakuwunika chitetezo chambiri cha anthu.Ngakhale zoyeserera zingapo zamalonda zamagazi a peptide zapezeka posachedwa, aliyense pano amafunikira phlebotomist kuti apeze magazi, kuchepetsa kupezeka ndi kukula kwake.Makina amagazi a capillary amagwiritsidwa ntchito kwambiri kudziwa kuchuluka kwa ma antibodies a SARS-CoV-2 pagulu.Tidasintha kuyesa kwamagazi a capillary kuti tiyese kuyesa kwamphamvu kwa peptide yamagazi kuti tiwunikire kuyambiranso kwa T cell ku SARS-CoV-2 mapuloteni opangidwa ndi SARS-CoV-2 ma antibodies enieni.M'malo mwake, kuyeza kophatikizana kwa ma antibodies enieni a SARS-CoV-2 ndi maselo a T omwe ali m'magazi a capillary kumakhala kokongola kwambiri: (i) kumachepetsa kufunika koyezetsa magazi kangapo pa aliyense wotenga nawo mbali, (ii) kumakulitsa chidziwitso cha omwe akutenga nawo mbali komanso kumvetsetsa;(iii) kuwongolera kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe ka kayendetsedwe kake ndi kuchepetsa kubwerezabwereza, (iv) kuchepetsa kuwonongeka kwa chilengedwe monga momwe zinthu zogwiritsira ntchito mu labotale zimafunikira komanso kupereka zitsanzo.Ngakhale kuti IFN-γ reactivity inali yofanana pakati pa zitsanzo za magazi a venous ndi capillary, zinkawoneka kuti ndizochepa m'magazi a capillary blood cohort of participants (mkuyu 4a) poyerekeza ndi venous blood cohort (mkuyu 2a).Makhalidwe a IFN-γ Pali mafotokozedwe angapo okhudzana ndi izi, monga, chiwerengero chachikulu cha omwe ali ndi comorbidities omwe amafunikira immunosuppressive therapy adalowetsedwa mu gulu la capillary blood sampling cohort (Table 1) ndi Viability ndi / kapena ntchito ya maselo a T omwe amachokera ku mitsempha. zitsanzo zingakhale zotsika, makamaka poganizira za kusungidwa kwa nthawi yaitali kwa zitsanzo musanayambe kukondoweza kwa peptide.
Katemera wa COVID-19 yemwe akupezeka pano akupereka chitetezo chabwino kwambiri ku matenda oopsa kwa ambiri omwe amalandila pakadutsa miyezi 6 atalandira katemera8.Chosangalatsa ndichakuti, ngakhale kuti katemera wa SARS-CoV-26,7 anali wosasinthika bwino, mayankho a T-cell omwe adabwera chifukwa cha katemera wa SARS-CoV-2 adakhalabe achangu, pomwe ena 25 adatulukira.Zomwe timapereka pano zikuwonetsa kufunikira kwa kuwunika kozama kwa katemera wa immunogenicity, ndikuwunikira katemera wokhala ndi chitetezo chokwanira cha T-cell kuti ateteze matenda adzidzidzi komanso kufalikira kwa kachilomboka mosalekeza.Tidawonanso kuti anthu ambiri osatemera omwe adalembetsedwa m'gulu la capillary anali ndi chidwi kwambiri ndi ma SARS-CoV-2-specific T cell (ndi N-binding IgG) mosasamala kanthu za katemera wakale, womwe mwina umakhala chifukwa cha matenda am'mbuyomu.M'malo mopereka katemera kwa anthu oyenerera, chiopsezo chawo chotenga kachilombo chiyenera kuyesedwa malinga ndi momwe alili panopa komanso zomwe asankha.
Zochepa za kafukufukuyu zikuphatikiza chitsimikiziro chakuti otenga nawo mbali adadziwonetsa okha kuti ali ndi kachilombo ka SARS-CoV-2 atatolera magazi kuti adziwe kufunikira kwa chitetezo chamthupi;ena atha kukhala ndi matenda asymptomatic ndipo sangathe kuyezetsa PCR ndi/kapena lateral flow flow ya COVID-19.Zolemba zathu zinalibenso zambiri zokhuza mankhwala omwe adatenga nawo gawo panthawi yomwe amayesa magazi.Kuphatikiza apo, popeza onse omwe adatenga nawo gawo adangowonetsa zofooka / zolimbitsa thupi zokha kapena opanda zizindikiro, sikunali kotheka kuzindikira mayankho a chitetezo chamthupi pazidziwitso zathu zomwe zidaneneratu za chiwopsezo chowonjezeka cha matenda akulu ndikugonekedwa m'chipatala ku COVID-19.Komabe, kupezeka kwa mayankho a CD8+ T cell motsutsana ndi ma epitopes enieni a nucleocapsid kwalumikizidwa posachedwa ndi chitetezo ku COVID-1926.Kuphatikiza apo, kuyesa komwe kukugwiritsidwa ntchito pano sikunayese mayankho a T cell ku mapuloteni omwe sanatchulidwe a SARS-CoV-2 omwe posachedwapa awonetsedwa kuti amadziunjikira mwabwino kwa ogwira ntchito yazaumoyo omwe adakumana ndi odwala omwe ali ndi kachilomboka.Kutengera ntchitoyi, chifukwa cha kuchuluka kwa kufalikira kwa anthu ammudzi panthawi yolemba ntchito komanso mwayi wopezeka ndi matenda okhudzana ndi anthu, kuchuluka kwa ma SARS-CoV-2 ma cell enieni a T omwe amapezeka pamayeso athu akuwonekanso kuti angathe kuloledwa.matenda a subclinical m'magulu athu.Pomaliza, sitinayeze kupanga kwa interleukin 2 ndi ma T cell chifukwa ntchito yathu yam'mbuyomu idawonetsa kusazindikirika bwino kwa mayankho a T-cell a SARS-CoV-214, ngakhale mayankho achindunji a IL-2 atha kuwonetsa kusinthika komwe kunalipo kale.maselo okhudzana ndi chitetezo ku matenda a SARS-CoV-211.
Kuphatikizidwa pamodzi, izi zikuwonetsa kufunikira kofunikira kwa maphunziro a nthawi yayitali omwe amaphatikiza mayankho a SARS-CoV-2-specific T cell mumiyeso ya chitetezo chamthupi la anthu.Izi zitha kuthandizidwa popanga mayeso atsopano a magazi a capillary omwe amayesa kuyankha kwa T-cell.
Ntchito yofufuzayi idalemba anthu kuyambira February 2021 mpaka Marichi 2022. Gulu la opereka athanzi (n = 148) omwe adapereka magazi a venous anali makamaka ogwira ntchito ku yunivesite ndi ophunzira omwe adachita nawo ntchito yowunikira COVID-19 ku Cardiff University kapena ogwira ntchito pasukulu ya pulaimale ku. Cardiff.Onse omwe adatenga nawo gawo anali athanzi ndipo sananene kuti amwa mankhwala oletsa chitetezo chamthupi (onani Gulu 1 kuti muwone mawonekedwe).Gulu la otenga nawo mbali omwe adapereka zitsanzo za magazi a capillary anali ndi onse opereka mwaufulu (azaka 18+) ochokera ku UK konse.Pakati pa Januware 24 ndi Marichi 14, 2022, anthu 342 adalembetsa nawo kafukufukuyu, omwe 299 adapereka zitsanzo zamagazi ku labotale.Ambiri omwe adatenga nawo gawo adakhalabe osalandira katemera komanso/kapena adanenanso za zovuta zina, kuphatikiza matenda a autoimmune ndi khansa (onani Table 1 kuti muwone mawonekedwe).Kafukufukuyu adalandira chivomerezo cha chikhalidwe kuchokera ku Newcastle ndi North Tyneside 2 Research Ethics Committee (ID IRAS: 294246) ndi Cardiff University School of Medicine Research Ethics Committee (SREC ref: SMREC 21/01).Onse omwe adatenga nawo mbali adapereka chilolezo chodziwitsidwa asanaphatikizidwe.Ophunzira sanalandire chipukuta misozi chifukwa chochita nawo kafukufukuyu.
Zitsanzo zamagazi a venous zidapezedwa ndi venipuncture mu 6 kapena 10 ml ya lithiamu kapena sodium heparin vacutainers (BD).Miyezo yamagazi a capillary idapezedwa ndi lancet chala ndikusonkhanitsidwa mu heparin microcontainers (BD).Magazi osachepera 400 µl amafunika;chitsanzo chilichonse chocheperapo chidzakanidwa.Zifukwa zina zokanira zitsanzo zinaphatikizapo coagulation yaikulu ndi / kapena hemolysis ndi kulephera kusonkhanitsa plasma viscous kusanthula (Supplementary Fig. 5).Ma 299 amagazi a capillary analipo kuti athe kuyesa mayankho a antibody, omwe zitsanzo 270 zinaliponso zowunika mayankho a T cell.
Mayankho amtundu wa T-cell a SARS-CoV-2 adawunikidwa pogwiritsa ntchito COVID-19 Immuno-T assay (ImmunoServ Ltd) ndipo adachita monga momwe adafotokozera kale14.Mwachidule, 6 ml kapena 10 ml ya sodium heparin (BD) venous vacutainer (BD) adatengedwa kuchokera kwa wophunzira aliyense ndikusinthidwa mu labotale mkati mwa maola 12 atatolera magazi.Ngakhale kuti zitsanzo zambiri zidakonzedwa mkati mwa maola 24, magazi a 400-600 μl a heparinized microbleeding (BD) adasonkhanitsidwa mkati mwa maola 48 atatengedwa ndi chala.Magazi a venous ndi/kapena capillary adalimbikitsidwa ndi maiwe a peptide apadera a SARS-CoV-2 (zosiyana zamtundu wakuthengo) monga tafotokozera kale14.Laibulale ya peptide iyi ili ndi zotsatizana za 420 15-mer zokhala ndi ma amino acid 11 opitilira muyeso (S1 ndi S2) (S; NCBI protein: QHD43416 1), nucleocapsid phosphoprotein (NP; NCBI protein: QHD43423 2) ndi membrane glycoprotein ; Puloteni ya NCBI: QHD43419 1) zotsatizana (zotchedwa "S-/NP-/M-combinatorial peptide library").Ma peptides onse adayeretsedwa ku> 70%, kusungunuka m'madzi osabala ndipo amagwiritsidwa ntchito pomaliza 0.5 μg/ml pa peptide.Zitsanzo zidakulungidwa pa 37 ° C kwa maola 20-24.Machubuwo anali centrifuged pa 5000 × g kwa mphindi 3 ndipo ~ 150 µl ya plasma inasonkhanitsidwa kuchokera pamwamba pa magazi aliwonse.Sungani zitsanzo za plasma pa -20 ° C kwa mwezi umodzi musanagwiritse ntchito zofufuza za cytokine / antibody.
IFN-γ idayesedwa pogwiritsa ntchito IFN-γ ELISA MAX Deluxe Set (BioLegend, catalog number 430116) ndipo idachitidwa motsatira malangizo a wopanga.Atangosiya njira yothetsera (2N H2SO4) idawonjezedwa, microplate idawerengedwa pa 450 nm pogwiritsa ntchito owerenga mbale ya BioLegend Mini ELISA.IFN-γ idayesedwa ndi ma curve wokhazikika pogwiritsa ntchito GraphPad Prism.Makhalidwe omwe ali pansi pa malire otsika omwe amayesedwa adalembedwa ngati 7.8 pg/ml, zomwe zili pamwamba pa malire apamwamba a mayesowo zinalembedwa ngati 1000 pg/ml.
Anti-SARS-CoV-2 RBD/S1/S2/N IgG ma antibodies adayesedwa pogwiritsa ntchito gulu la Bio-Plex Pro Human IgG SARS-CoV-2 4-plex panel (Bio-Rad, cat. no. 12014634) ndipo amalembedwa molingana ndi malangizo opanga .malangizo .Zitsanzo zofotokozera zamtengo wapatali kuposa malire a kuchuluka kwake zidawunikidwanso pa 1: 1000 dilution.Avereji yamphamvu ya fluorescence ya mikanda idayezedwa pa chida cha Bio-Plex 200 (Bio-Rad).Kuchuluka kwa ma antibodies kumawerengedwa ndi VIROTROL SARS-CoV-2 single control assay (Bio-Rad) ndikusinthidwa kukhala WHO/NIBSC 20/136 International Reference Standard Units (BAU/mL) pogwiritsa ntchito calibration factor ya wopanga.
RBD ndi S1 ​​subunit-specific neutralizing antibodies motsutsana ndi SARS-CoV-2 zakuthengo ndi mizere ya delta (B.1.617) SARS-CoV-2 mizere idayezedwa pogwiritsa ntchito Bio-Plex Pro Human SARS-CoV-2 Variant Neutralization Antibody Kit (Bio -Rad, gawo la 12016897), malinga ndi malangizo a wopanga.Yezerani kuchuluka kwa fluorescence pa Bio-Plex 200 (Bio-Rad) ndikuwerengera kuchuluka kwa zopinga (ie, neutralization) pogwiritsa ntchito njira iyi:
Mayesero osalowerera ndale a SARS-CoV-2 adachitidwa monga momwe adafotokozera28.Mwachidule, 600 PFU yamtundu wakuthengo SARS-CoV-2 idalumikizidwa ndi 3-fold serial dilution ya plasma mobwereza kwa ola limodzi pa 37 ° C.Chosakanizacho chinawonjezeredwa ku maselo a VeroE6 kwa maola 48.Ma Monolayers anali opangidwa ndi 4% paraformaldehyde, permeabilized ndi 0.5% NP-40 ndi incubated kwa ola la 1 mu blocking buffer (PBS yomwe ili ndi 0.1% pakati ndi 3% mkaka wosakanizidwa).Anti-nucleocapsid 1C7, Stratech) adawonjezedwa kuti atseke chotchinga kwa ola limodzi pa kutentha kwapakati.Pambuyo kutsuka, anti-mouse IgG-HRP, Pierce) adawonjezedwa kutsekereza buffer kwa ola limodzi.Ma Monolayers adatsukidwa, kupangidwa pogwiritsa ntchito Sigmafast OPD ndikuwerenga pa owerenga mbale ya Clariostar Omega.Zitsime zopanda kachilombo, zopanda kachilombo koma zopanda ma antibodies, ndi sera yokhazikika yowonetsa zochitika zapakatikati zidaphatikizidwa mukuyesera kulikonse monga zowongolera.
Kusanthula kwachiwerengero kunachitika mu GraphPad Prism (mtundu 9.4.1).Chizoloŵezi cha deta chinayesedwa pogwiritsa ntchito mayeso a Shapiro-Wilk.Njira zopanda parametric zidagwiritsidwa ntchito pofananiza zonse.Mayeso a Mann-Whitney adagwiritsidwa ntchito pazitsanzo zopanda pake.Mayesero onse anali a mbali ziwiri ndi gawo lofunikira la P ≤ 0.05.
Kusanthula koyambirira kwa dataset kudachitika mu R (mtundu 4.0.3).Izi zikuphatikiza kukulitsa kwa Spearman's univariate rank correlation matrix, pomwe kulumikizana pakati pamitundu iwiri kumayimiridwa ndi kukula ndi mtundu wa mabwalo.Kufunika kwachiwerengero pakati pa mayanjano kunawerengedwa pogwiritsa ntchito Spearman's rho, pomwe ma ≤0.05 amaonedwa kuti ndi ofunika.Kufananitsa komwe sikunali kofunikira pakuwerengera sikunaphatikizidwe ku matrix ndikuyika ma cell opanda kanthu.P-makhalidwe adasinthidwa kwa mafananidwe angapo pogwiritsa ntchito kukonza kwa Holm.Mtundu wabinary logistic regression model unagwiritsidwa ntchito kutengera zomwe zasintha mu dataset poyankha zabwino ku COVID-19.Mayankho a IFN-γ T cell ndi anti-RBD/S1/S2/N IgG titer scores adasinthidwa kukhala zinthu, pomwe munthu aliyense adapatsidwa gawo loyenera pagawo lililonse.Pambuyo pake, chitsanzo choyambirira cha kafukufuku chinapangidwa pogwiritsa ntchito ntchito ya glm mu phukusi la chiwerengero (V4.0.3).Magawo azovuta omwe amachokera ku mtundu woyambirirawu adatengedwa kuchokera ku ma coefficients amtunduwo pogwiritsa ntchito 'odd_plot' mu phukusi la OddsPlotty (V1.0.2).Popanga mtundu wotsimikizira, tidagwiritsa ntchito "bestglm" kuchokera pa phukusi la bestglm (V0.37.3) kuti tichepetse kukondera kwa ogwiritsa ntchito ndikuwonetsetsa kuti gawo labwino kwambiri la zolosera zitha kusankhidwa.Njira yomwe idasankhidwa inali "yokwanira" ndipo mfundo yomwe idagwiritsidwa ntchito poyesa kukwanira kwachitsanzo inali AIC.Njira yofananira yomwe tafotokozayi idagwiritsidwa ntchito kuti mupeze kuchuluka kwa zovuta.
Kuti mumve zambiri za kapangidwe ka maphunziro, onani nkhani ya Nature yolumikizidwa ndi nkhaniyi.
Makalata ndi zopempha za zipangizo ziyenera kutumizidwa kwa Dr. Martin Scarr kapena Pulofesa Andrew Godkin.Nkhaniyi imapereka deta yoyambirira.
Khodi ya R yomwe imagwiritsidwa ntchito popanga mitundu yowerengera imapezeka poyera popanda kufunsa29.Zambiri zosindikizanso ndi zilolezo zitha kupezeka pa www.nature.com/reprints.
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