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Kuhili ʻole 347 Coil Tube Chemical Composition
ʻO ka hui kemika a me nā waiwai mechanical o ke kila kila 347 coil tube penei:
- Kalapona – 0.030% ka nui
- Chromium – 17-19%
- Nikela – 8-10.5%
- Manganese – 1% ka nui
| Papa | C | Mn | Si | P | S | Cr | N | Ni | Ti |
| 347 | 0.08 ka nui | 2.0 ka nui | 1.0 ka nui | 0.045 ka nui | 0.030 ka nui | 17.00 – 19.00 | 0.10 ka nui | 9.00 – 12.00 | 5(C+N) – 0.70 ka nui |
Kuhili 'ole 347 Coil Tube Mechanical Pono
Wahi a ka Stainless Steel 347 Coil Tube Manufacturer, Mechanical Properties o 347 Coil Tube:
- Ka ikaika ʻo Tensile (psi) - 75,000 min
- Ka ikaika hua (psi) - 30,000 min
- Elongation (% in 2″) – 25% min
- Paʻa Brinell (BHN) – 170 ka nui
| Mea waiwai | ʻO ka mānoanoa | Lae hehee | Ikaika U'i | Ka ikaika o ka hua (0.2%offset) | ʻO ka lōʻihi |
| 347 | 8.0 g/cm3 | 1457 °C (2650 °F) | Psi – 75000 , MPa – 515 | Psi – 30000 , MPa – 205 | 35 % |
Nā noi a me ka hoʻohana ʻana i ka pahu hao hao 347 coil
- ʻO ke kila kila 347 paipu wili i hoʻohana ʻia ma nā hale kō.
- ʻO ke kila kila 347 Puka Coil i hoʻohana ʻia i ka Fertilizer.
- ʻO ke kila kila 347 Coil Tube i hoʻohana ʻia ma ka ʻoihana.
- ʻO ke kila kila 347 Coil Tube i hoʻohana ʻia i nā mea kanu mana.
- ʻO ke kila kila 347 Coil Tube i hoʻohana ʻia i ka meaʻai a me ka waiu.
- ʻO ke kila kila 347 Puka Coil i hoʻohana ʻia i loko o ka mea kanu ʻaila a me ke kinoea.
- ʻO ke kila kila 347 Coil Tube Manufacturer i hoʻohana ʻia i ka ʻoihana ShipBuilding.
Manaʻo ʻia nā cell T kikoʻī SARS-CoV-2 e pale aku i ka maʻi a me ka holomua o COVID-19, akā ʻaʻohe mea hōʻike pololei no kēia.Ma ʻaneʻi, ua hoʻohālikelike mākou i nā ana koko holoʻokoʻa o SARS-CoV-2-specific interferon-γ positive T cell me nā hopena hoʻāʻo diagnostic COVID-19 maikaʻi (PCR a/a i ʻole kahe lateral) i loko o 6 mau mahina o ka hōʻiliʻili koko o Lian.Ma waena o 148 mau mea komo i hāʻawi i nā hōʻailona koko venous, ʻoi aku ka kiʻekiʻe o ka pane o ka cell T cell SARS-CoV-2-specific i ka poʻe i mālama ʻia ma mua o ka poʻe i loaʻa i ka maʻi (P <0.0001).% pilikia o ka ma'i, oiai ua hoemi ka ikaika nui i keia pilikia i 5.4%.Ua hoʻonui ʻia kēia mau hopena i kahi hui 299 hou aʻe i hoʻāʻo i kahi hōʻike koko capillary hiki ke hoʻomaʻamaʻa i ke komo ʻana i ka ʻikepili palekana T-cell lehulehu (14.9% vs. 4.4%).No laila, hiki i ke ana ʻana o nā pūnae T kikoʻī no SARS-CoV-2 ke wānana i ka hopena o ka maʻi a pono e loiloi ʻia i ka wā e nānā ana i ke kūlana pale ʻana o kēlā me kēia kanaka.
ʻO ke ana ʻana a me ka hoʻomaopopo ʻana i ka pane ʻana i ka maʻi SARS-CoV-2 he mea nui ia e hoʻomohala i nā hoʻolālā e hiki mai ana e hōʻemi i ka olakino ākea a me ka hopena o ka hoʻokele waiwai o nā maʻi maʻi COVID-19 e hiki mai ana.ʻO ka ʻike ʻana i nā correlates immune e hāʻawi i ka ʻike koʻikoʻi e pili ana i ka maʻalahi o ka heluna kanaka i ka maʻi maʻi viral, hiki paha i ka ʻōlelo mua ʻana o nā hale hoʻokipa kiʻekiʻe, a e ʻae pū i ka poʻe e hoʻokele pono i ko lākou pilikia o ka maʻi a me ka pilikia o ka hoʻopili ʻana i nā poʻe ʻē aʻe.Ua hōʻike koʻikoʻi ka nānā ʻana i ka immunocompromised e loiloi i ka maikaʻi o nā kano COVID-19 i nā mea maʻi olakino a kiʻekiʻe loa 1,2,3 ʻoi loa i nā mutants SARS-CoV-24, a ʻo ka ʻike ʻana o ka immunocompromised ʻo ia ka mea e pono ai e hoʻoikaika i ka Immunity E hoʻopaʻa ʻia a pale aku. nā ʻūhā e hiki mai ana .
ʻO ke kiʻekiʻe o ka pale ʻana o kahi kanaka i ka maʻi SARS-CoV-2 e pili ana i nā kumu he nui: ka viral load i ka manawa o ka hoʻolaha ʻana, nā ʻano maʻi virus, nā makahiki, ke kūlana o ka maʻi maʻi / maʻi maʻi, nā comorbidities, nā lāʻau lapaʻau, a ʻo ka mea nui loa, ka maʻi anti-SARS-CoV. .2 hiki mai ka pane immune adaptive i ka manawa i ʻike ʻia i ka maʻi maʻi5.ʻO ka loiloi ʻana i ka pane ʻana i ka maʻi i ka maʻi SARS-CoV-2 a/a i ʻole ka hoʻopaʻa ʻana ua nānā ʻia i nā serological assays e ana i ka loaʻa ʻana o nā antibodies kikoʻī no kahi protein structural (e laʻa, spike glycoprotein).Eia nō naʻe, ʻo ka hele ʻana a i ʻole ka haʻalele ʻana o nā antibodies wale nō ʻaʻole ia e hoʻoholo pololei i kahi pane pale pale, no ka mea, ua hoʻemi nui ʻia nā pane i ka manawa 6 a me ka neutralization o nā ʻano like ʻole SARS-CoV-2 i ka hoʻihoʻi ʻana a i ʻole nā mea paʻi pālua i ka hana nāwaliwali, hiki ke alakaʻi i kahi nui. ka helu o nā maʻi maʻi 7.ʻOiaʻiʻo, ua emi ka pale ʻana i ka hōʻailona COVID-19 i hoʻokumu ʻia e ka ʻano ʻano Omicron (B.1.1.529) ma kahi o 10% ma hope o 4-6 mau mahina wale nō o ka hoʻopaʻa ʻana i ka mRNA, ʻoiai ua hoʻomau ka pale ʻana i nā maʻi koʻikoʻi> 68% no ka liʻiliʻi 7 mahina8.ʻO ke ana ʻana i nā pane cell T cell adaptive, e hāʻawi ana i ka pale lōʻihi mai ka maʻi maʻi viral, ʻo ia ka hōʻailona maikaʻi loa o ka hiki ke loaʻa i ka maʻi SARS-CoV-2, a no laila he hōʻailona ʻoi aku ka maikaʻi o ka hopena o ka hoʻāʻo ʻana i ka maikaʻi no COVID-199, ʻoiai ʻo T kikoʻī. hiki i nā pūnaewele ke pale i ka maʻi.me ka seroconversion10,11.Eia nō naʻe, ua emi iki ka nānā ʻana o ke ana ʻana o nā pane T cell ma muli o nā pilikia me ka ʻano hana a me nā pilikia logistical i ka loaʻa ʻana a me ka lawe ʻana i nā laʻana koko venous, ʻoi aku hoʻi i ka wā e hana ana i nā haʻawina nānā nui e loiloi i ka maikaʻi o ka maʻi a me ka nānā ʻana i ka pale.Eia nō naʻe, hōʻike ka poʻe i hoʻopaʻa ʻia i ka hana paʻa T cell e kūʻē i nā ʻano like ʻole SARS-CoV-2, hiki ke hoʻopau i ka nalowale o ka antibody reactivity e kaupalena i ka paʻakikī o COVID-1912,13.
Ma ʻaneʻi, ʻimi mākou e hoʻomaopopo inā hiki i kahi ana hoʻokahi o ka pane cell SARS-CoV-2 T ke wānana i ka pilikia maoli o ka maʻi SARS-CoV-2 i loko o 6 mau mahina o ka hoʻāʻo ʻana i ke koko, me ka nānā ʻole i nā mea i hoʻopili mua ʻia.I mea e ho'āʻo ai i ka hoʻāʻo ʻana o ka T cell i ka puka kiʻekiʻe a pili i nā noiʻi ʻoi aku ka nui, ua hoʻāʻo pū mākou e hana i ka hōʻike miniaturized i hiki ke hana ʻia me ka hoʻohana ʻana i kahi laʻana koko capillary fingerstick.
Ua ana mākou i nā pane pale kino a me ka humoral i nā mea hāʻawi olakino me ka hoʻohana ʻana i ka ʻike hui ʻana o nā pūnana SARS-CoV-2 T a me nā antibodies IgG e pili ana i ke koko venous holoʻokoʻa (no nā hiʻohiʻona komo, e ʻike iā Malaki 2022 14. Ua hoʻoholo ʻia nā pane T-cellular kikoʻī ma ke ana ʻana i nā pae interferon-γ (IFN-γ) plasma ma hope o ka hoʻoulu ʻana i ke koko holoʻokoʻa me ka peptide SARS-CoV-2 (e like me ka wā ma mua, refs. 14,15,16,17,18) a me nā pane IgG pili. me ka nucleocapsid (N) ua hoʻonui ʻia i loko o ka poʻe i hōʻike i ka maʻi ma mua, ʻoiai ʻoi aku ka kiʻekiʻe o nā pane ʻelua i nā mea hāʻawi mua ʻole i hoʻopaʻa ʻia, ʻoi loa i loko o ke kino (Fig. 1a, b). Nā pane IgG e kūʻē i ka spike glycoproteins (RBD, S1, S2) ʻoi aku ka kiʻekiʻe loa i nā mea hāʻawi i hoʻopaʻa ʻia i ka maʻi ma mua (Figure 1c–e).
Ua ana ʻia nā pane cell IFN-γ+ kikoʻī SARS-CoV-2 e ka hoʻāʻo ʻana i ke koko holoʻokoʻa a hoʻokumu ʻia ma ka hoʻopaʻa ʻana o nā poʻe hui a me ke kūlana maʻi SARS-CoV-2 ma mua (i hōʻoia ʻia e ka PCR a / a i ʻole ka hoʻāʻo ʻana o ka kahe lateral)' Vac + /Inf +' n = 60 ('ōmaʻomaʻo), 'Vac + /Inf-' n = 82 (uliuli), 'Vac-/Inf +' n = 4 (melemele), 'Vac-/Inf-' n = 1 (ʻaʻole i hoʻohana ʻia).SARS-CoV-2-specific IgG binding reactions target nucleocapsid (“N”) (b; ****P <0.0001, **P = 0.0016), spiked receptor-binding domain (“RBD”) (c; ** P = 0.0022, *P <0.015), ʻāpana spike 1 (“S1”) (d; ***P = 0.0005, *(Vac + /Inf+ vs. Vac + /Inf-) P = 0.022, *(Vac- /Inf+ vs. Vac+/Inf-) P = 0.012) a me ka piko subunit 2 (“S2”) (e) ua ana ʻia e nā hoʻāʻo koko holoʻokoʻa venous a ma muli o ka hoʻopaʻa ʻana o ka mea komo a me ka SARS -CoV-2 mua (i hōʻoia ʻia e PCR a// a i ʻole ka hoʻāʻo ʻana o ke kahe lateral) kūlana infectious.'Vac + /Inf +' n = 60 ('ōmaʻomaʻo), 'Vac + /Inf-' n = 71-82 (uliuli), 'Vac-/Inf +' n = 4 (melemele).Hoʻohālikelike ʻia me ka hoʻohana ʻana i ka hoʻāʻo Kruskal-Wallis, i hoʻoponopono ʻia no nā hoʻohālikelike lehulehu me ka hoʻohana ʻana i ka hoʻāʻo Dunn.Hōʻike ʻia ka ʻikepili ma ke ʻano he kiʻi (laina waena ma waena, palena kiʻekiʻe ma 75th percentile, palena haʻahaʻa ma 25th percentile) me nā ʻumikū ma ka liʻiliʻi a me ka nui loa.Hōʻike kēlā me kēia kiko i kahi mea hāʻawi.Hāʻawi ʻia ka ʻikepili maka ma ke ʻano o nā faila ʻike maka.
Ma hope o ka hoʻāʻo ʻana i ke koko, ua noi ʻia nā mea komo e hōʻike ponoʻī iā lākou iho i ka PCR maikaʻi a/a i ʻole nā hopena hoʻāʻo ʻana o ka kahe lateral no COVID-19;inā i hōʻike maikaʻi ʻia nā mea komo ma waena o 1 Kepakemapa 2021 a me 29 Kekemapa 2021, ua manaʻo ʻia ua loaʻa iā lākou ka maʻi me Delta (B.1.617.2) ʻano coronavirus a me Omicron (B.1.1.529) i Public Health Wales ma hope o Dekemaba 29, 2021, i ka manawa lilo kēia koho o ka hopohopo.Ma waena o 148 mau mea hāʻawi loiloi, ʻike mākou i ka nui o ka maʻi o 26.3% (39/148) i loko o 6 mau mahina o ka hāʻawi ʻana i ke koko, 38 o lākou i loaʻa i ka lua a i ʻole ke kolu o ka maʻi o ka maʻi COVID-19 (ua loaʻa ka maʻi maʻi ma hope o Pfizer/BioNTech ( BNT162b2) mRNA a i ole AstraZeneca vaccine (ChAdOx1 nCoV-19));ua loaʻa pū kekahi mea hāʻawi i hoʻopaʻa ʻole ʻia.ʻO ka nui o ka SARS-CoV-2-specific IFN-γ-positive T cell pane i haʻahaʻa loa i ka poʻe i hōʻike i kahi hōʻike diagnostic maikaʻi no COVID-19 ma mua o nā mea hāʻawi ʻole ʻia (P <0.0001; Fig. 2a), ma muli o ka ʻO ka hoʻokomo maikaʻi ʻana i nā pane T cell ma o ka hoʻomaʻamaʻa ʻana i kekahi mau mea komo (P = 0.050; Hoʻohui Fig. 1).ʻAʻohe pilina ma waena o ka nui o ka pane IFN-γ+ T cell a me ka manawa i kahi hopena hoʻāʻo COVID-19 maikaʻi (Supplementary Figure 2).I ka hoʻohālikelike ʻana, ʻaʻole i kikoʻī ʻia nā pane RBD-, S1-, S2-binding IgG (Figures 2b-d) a i ʻole RBD-, S1-neutralizing antibody pane no ka wild-type a i ʻole delta SARS-CoV-2 (B.1.617).) (Supplementary Fig. 3) hiki ke hoʻokaʻawale i waena o ka poʻe i pilikia i ka maʻi.Eia naʻe, pili nā pane haʻahaʻa N-linked IgG kūʻē iā SARS-CoV-2 me ka pilikia o ka maʻi COVID-19 (P = 0.0084; Kiʻi 2e);ʻO ka poʻe i hōʻike maikaʻi ʻia he 85% ka liʻiliʻi (P = 0.00035; OR 0.15, 95).% CI: 0.047-0.39 (Helu 4).
ʻO nā laʻana koko Venous mai nā mea hāʻawi olakino (n = 148) i loiloi i ka SARS-CoV-2-specific IFN-γ+ T-cell pane (a; ****P <0.0001) a me ka hoʻopaʻa ʻana o ka mea loaʻa Spike i ka SARS-CoV kikoʻī. -2 hoʻoulu.domain (“RBD”) (b), spike 1 subunit (“S1″) (c), spike 2 subunit (“S2″) (d), and nucleocapsid (“N”) (e; **P = 0.0084 ) .Ua ʻike ʻia nā poʻe i hoʻāʻo maikaʻi ʻia no COVID-19 (PCR a/a i ʻole ke kahe ʻaoʻao);ua loaʻa nā maʻi āpau i loko o 6 mau mahina ma hope o ka hoʻāʻo ʻana i ke koko.Hoʻohālikelike ʻia me ka hoʻohana ʻana i kahi hoʻokolohua Mann-Whitney ʻelua huelo.Hōʻike ʻia ka ʻikepili ma ke ʻano he kiʻi (laina waena ma waena, palena kiʻekiʻe ma 75th percentile, palena haʻahaʻa ma 25th percentile) me nā ʻumikū ma ka liʻiliʻi a me ka nui loa.Hōʻike kēlā me kēia kiko i kahi mea hāʻawi.ʻAʻole nui ka ns.Hōʻike ka wela wela f i ka hoʻopili ʻana o Spearman ma waena o nā mea hoʻololi no ka ʻikepili i kuhikuhi ʻia.Ua hoʻokaʻawale ʻia nā hoʻohālikelike ʻaʻole koʻikoʻi koʻikoʻi mai ka matrix a hōʻailona ʻia me nā cell blank.Hāʻawi ʻia ka ʻikepili maka ma ke ʻano o nā faila ʻike maka.
Ua noʻonoʻo ʻia ka ʻoki ʻoki maikaʻi diagnostic preset o 14 no ka loiloi ʻana i ka pilikia o ka maʻi hou ʻana, no laila ua hoʻokumu ʻia nā pae interquartile e hoʻokumu i nā ʻāpana pilikia.ʻO ke kumu hoʻohālike helu, ka mea i hoʻokomo wale i nā mea hoʻololi i loaʻa ka hopena koʻikoʻi i nā hopena, ua hōʻike ʻo ka nui o ka pane ʻana o ka cell SARS-CoV-2-specific IFN-γ+ T ʻo ia ka biomarker immune koʻikoʻi no ka hoʻoholo ʻana i ka manawa o ke kanaka. hoʻāʻo ʻia no COVID.-19 maikaʻi (Figure 2f a me Hoʻohui Kiʻi 4).ʻO nā poʻe maʻi me kahi SARS-CoV-2 kikoʻī IFN-γ+ T cell pane i ke kolu (194-489 pg/ml IFN-γ) a me ka hā (>489 pg/ml IFN-γ) quartiles 65% (P = 0.055; OR 0.35, 95% CI: 0.11-1.00) a me 90% (P = 0.0050; OR 0.098, 95% CI: 0.014-0.42) i ʻoi aku ka nui o nā mea komo.ʻOi aku ka liʻiliʻi o nā manawa (Hoʻohui Fig. 4).ʻO ka holoʻokoʻa, ʻo nā mea komo me ka SARS-CoV-2 kikoʻī T cell pane mai ke koko venous ≤79 pg/mL IFN-γ he 43.2% ka hopena o ka maʻi breakthrough ma 6 mau mahina, hoʻohālikelike ʻia me ka pane> 489 pg/mL.ml o IFN-γ i loaʻa i ka maʻi o 5.4% (papa 2).
Ua kaupalena ʻia ka hoʻāʻo ʻana o ke koko holoʻokoʻa ma muli o ka pono o ka hōʻiliʻili laʻana e ka phlebotomist.No ka hoʻonui ʻana i ka loaʻa ʻana o ka cell T a me ka hoʻāʻo ʻana o IgG no SARS-CoV-2, ua hoʻomohala ʻia kahi ʻano hana hoʻohālike koko capillary ʻē aʻe e hiki ai i nā poʻe komo ke kiʻi i nā laʻana koko manamana lima ma ka home.I ka maikaʻi o kā mākou ʻike, ʻaʻohe mea i hōʻike mua ʻia e pili ana i ke ana ʻana o ka hana antigen-specific T cell i nā ʻano koko capillary.Ua hōʻike mua ʻia kahi pilina ikaika ma waena o nā helu lymphocyte i loaʻa me ka hoʻohana ʻana i nā laʻana koko capillary a me venous.Eia kekahi, ua hōʻike ʻia ua hoʻohana ʻia nā hoʻokolohua holoʻokoʻa e pili ana i ke koko e ana ana i nā pane cell T cell SARS-CoV-2-specific i ka 320 μL o ke koko venous wale nō, 20 e hoʻopau ana i nā hopohopo e pili ana i ka pinepine o nā pūnae T progenitor i nā ʻāpana koko capillary.
Ua hoʻohana mākou i kēia kiʻekiʻe-throughput standardized collaborative assay o SARS-CoV-2 T cell a me IgG antibodies e pili ana i ke koko holoʻokoʻa capillary e ana i ka pane ʻana i ka cellular a me ka humoral immune pane i nā poʻe i komo me nā ʻano like ʻole a me ke kūlana maʻi / maʻi ma mua (Papa 1).kiʻi ʻia mai ka UK ma waena o 24 Ianuali a me 14 Malaki 202214. ʻO ka hapa nui (90.9%) o nā manamana lima i loaʻa pololei a hoʻouna ʻia i ka hale hana i loko o 24 mau hola o ka hōʻiliʻili ʻana.I kekahi mau hihia, ua loaʻa nā laʻana i loko o 48 mau hola o ke huki koko, akā ʻaʻole i hala kekahi o kēia mau laʻana i nā loiloi hoʻomalu maikaʻi a ʻaʻole i hoʻopilikia i nā ana holoʻokoʻa T cell a i ʻole nā ana antibody (Supplementary Fig. 5).ʻOiai aia nā ʻokoʻa i ka nui o ka SARS-CoV-2-specific IFN-γ+ T cell pane i ana ʻia i kēlā me kēia capillary a me ke koko venous i kekahi poʻe, ʻaʻohe ʻokoʻa koʻikoʻi holoʻokoʻa (P = 0.88; Hoʻohui Fig. 6 ).).
Ua hoʻonui nui ʻia nā pane cell IFN-γ+ T SARS-CoV-2-specific i nā poʻe i hoʻopaʻa ʻia i hōʻike pū kekahi i kahi maʻi ma mua (P = 0.0001), akā ʻaʻole i ʻoi aku ka kiʻekiʻe ma mua o ka poʻe hāʻawi hāʻawi ʻole i hoʻopaʻa ʻia ma mua (P = 0.19, Fig. 3a).).Ua ʻoi aku ka kiʻekiʻe o nā pane IgG e kūʻē i ka spike glycoprotein (RBD, S1, S2) i nā mea hāʻawi i hoʻopaʻa ʻia ma mua o nā mea hāʻawi ʻole ʻia, me ka nānā ʻole i ke kūlana maʻi ma mua (Figure 3b-d).ʻO ka mea e mahalo ai, ʻoi aku ka kiʻekiʻe o ka pane ʻana o N-bound IgG i nā poʻe i hoʻopaʻa ʻole ʻia i ka maʻi ma mua i hoʻohālikelike ʻia me nā poʻe i hoʻopaʻa ʻia, ʻoiai ʻaʻole i hiki ke koʻikoʻi (Figure 3e).Ma waena o nā mea hāʻawi i hoʻopaʻa ʻole ʻia a ʻaʻole i hoʻopaʻa ʻia i hōʻike iā lākou iho, 15 o 37 (40.5%) i komo i kūpono no N-linked IgG, ma luna o ka paepae i hoʻokumu mua ʻia o 2.0 BAU/mL14;ʻO kēia mau mea komo 15 He ʻumikūmālua o kēia mau maʻi i hoʻāʻo maikaʻi ʻia no ka pane ʻana o ka cell IFN-γ + T ma luna o ka paepae i hoʻokumu mua ʻia o 22.7 pg/mL IFN-γ14.No laila, ua maʻi mua ʻia kēia mau mea komo me SARS-CoV-2 a ʻaʻole i hoʻāʻo ʻia no COVID-19 ma muli o ke koho pilikino, nele o ka PCR a / a i ʻole nā mea hoʻoheheʻe lateral, a i ʻole asymptomatic.ʻOiai he pilina koʻikoʻi ma waena o nā pane T cell i IFN-γ+ a me N-linked IgG pae i nā mea hāʻawi ʻole i hoʻopaʻa ʻia (P = 0.0044; Kiʻi Hoʻohui, N-linked IgG pane i emi wikiwiki aʻe ma mua o ka pane IgG pili N, akā ʻo IFN-γ. + Ua mālama ʻia nā pane cell T me ka nānā ʻole i ke kūlana o ka hoʻopaʻa ʻana, ʻoiai he haʻahaʻa ka helu o nā mea hāʻawi i nā pule he 50 ma hope o ka hoʻokūkū (Supplementary Fig. 8). pūnaewele a me RBD e pili ana, ʻoiai nā poʻe i loaʻa i ʻelua mau kau o BNT162b2 a ukali ʻia e ka mRNA1273 revaccination ua hōʻike i nā kiʻekiʻe kiʻekiʻe o nā cell IFN-γ + T i ʻoi aku ka maʻalahi o ka SARS-CoV-2 ma mua o ka poʻe i loaʻa i ʻelua mau kau o ChAdOx1 a me BNT162b2 (Hoʻohui. Fig. 9) Eia kekahi, ua hōʻike ʻia nā comorbidities he liʻiliʻi ka ʻokoʻa holoʻokoʻa i ka nānā ʻana i nā pane cell T i hoʻohālikelike ʻia me nā mea hāʻawi olakino (Supplementary Fig. 10).
Ua ana ʻia nā pane cell IFN-γ+ T SARS-CoV-2 kikoʻī e ka hoʻāʻo ʻana i ke koko holoʻokoʻa a ua hoʻokumu ʻia ma ka hoʻopaʻa ʻana o nā poʻe komo a me ke kūlana infectious SARS-CoV-2 ma mua (i hōʻoia ʻia e ka PCR a/a i ʻole ka hoʻāʻo ʻana o ka kahe lateral).'Vac + /Inf +' n = 42 ('ōmaʻomaʻo), 'Vac + /Inf-' n = 158 (uliuli), 'Vac-/Inf +' n = 33 (melemele), 'Vac- /Inf-' n = 37 (hinahina).****P < 0.0001, ***P = 0.0001, *(Vac+/Inf- vs. Vac-/Inf-) P = 0.045, *(Vac-/Inf+ vs. Vac- /Inf-) P = 0.014 .ʻO SARS-CoV-2 nā hopena pili IgG kikoʻī i ka spike receptor binding domain (“RBD”) (b; ****P <0.0001, ns: ʻaʻole nui), spike subunit 1 (“S1”) (c; * * **P <0.0001, ns: ʻaʻole nui), spike subunit 2 (“S2″) (d; ****P <0.0001, ***P = 0.0005, *P = 0.016) a me ka nucleocapsid (“N”) (e; ****P <0.0001, ns ʻaʻole koʻikoʻi) ua ana ʻia me ka hoʻohana ʻana i ka nānā ʻana i ke koko holoʻokoʻa venous a ma muli o ka hoʻopaʻa ʻana o nā mea komo a me SARS-CoV-2 ma mua (i hōʻoia ʻia e ka PCR a me / a i ʻole ka nānā ʻana i ka kahe lateral) Ua māhele ʻia nā maʻi e kūlana.'Vac + /Inf +' n = 46 ('ōmaʻomaʻo), 'Vac + /Inf-' n = 182 (uliuli), 'Vac-/Inf +' n = 34 (melemele), 'Vac-/Inf-' n = 37 (hinahina).Hoʻohālikelike ʻia me ka hoʻohana ʻana i ka hoʻāʻo Kruskal-Wallis, i hoʻoponopono ʻia no nā hoʻohālikelike lehulehu me ka hoʻohana ʻana i ka hoʻāʻo Dunn.Hōʻike ʻia ka ʻikepili ma ke ʻano he kiʻi (laina waena ma waena, palena kiʻekiʻe ma 75th percentile, palena haʻahaʻa ma 25th percentile) me nā ʻumikū ma ka liʻiliʻi a me ka nui loa.Hōʻike kēlā me kēia kiko i kahi mea hāʻawi.Hāʻawi ʻia ka ʻikepili maka ma ke ʻano o nā faila ʻike maka.
E like me ka wā ma mua, ua noi ʻia nā mea komo e hōʻike i ka hopena PCR maikaʻi a/a i ʻole nā hopena kahe koko no COVID-19;e like me ka UK Health Agency, ua manaʻo ʻia ua loaʻa nā mea komo i ka maʻi o ka Omicron coronavirus (B.1.1.529) i ka manawa o ka hoʻāʻo ʻana i ka ʻano maʻi maʻi maikaʻi, ʻoiai ʻo ia ka ʻano nui ma UK i ka wā aʻo.Ma waena o 299 mau mea hāʻawi loiloi, ʻike mākou i ka nui o ka maʻi o 8.0% (24/299) i loko o ʻekolu mahina o ka hāʻawi ʻana i nā capillary, ʻehiku o lākou ʻaʻole i hoʻopaʻa ʻia.ʻO ka hapa o nā comorbidities ma waena o nā mea komo a pau he haʻahaʻa i ka poʻe i hoʻāʻo maikaʻi ʻia no COVID-19 (10.7%) ma mua o ka poʻe i hoʻāʻo maikaʻi ʻole no COVID-19 (24.4%, Papa 1), ʻo ia paha ma muli o ke ʻano o ka poʻe i komo me kekahi ʻoi aku ka makaʻala a pale aku i nā hopena e like me ka maʻi diabetes a me ka maʻi kanesa.E like me ka mea i ʻike ʻia i loko o kahi cohort koko venous, SARS-CoV-2-specific interferon-γ (IFN-γ) -positive T cell i ana ʻia i nā laʻana koko capillary mai nā poʻe e hōʻike ana i kahi hōʻike diagnostic maikaʻi no COVID-19.He haʻahaʻa loa ka nui o ka pane ma mua o nā mea hāʻawi ʻole ʻia (P = 0.034; Kiʻi 4a) ma muli o ka hoʻokomo maikaʻi ʻana o kahi pane T cell ma o ka hoʻopaʻa ʻana a / a i ʻole ka maʻi ma mua (Supplementary Figure 11).Pēlā nō, ʻaʻole ʻo RBD-, S1-, S2-binding IgG pane (Figures 4b–d) a i ʻole RBD-, S1-neutralizing antibody pane i kikoʻī no ka wild-type a i ʻole delta SARS-CoV-2 (B. 1.617).(Helu helu 12).Hiki ke ʻike ʻia ka poʻe me ka pilikia nui o ka maʻi.I ka hoʻohālikelike ʻana i ka cohort venous, ʻaʻole hoʻokaʻawale nā pane IgG pili i ka COVID-19 (Figure 4e), e hōʻike ana e hoʻonui ka ʻano Omicron (B.1.1.529) i ka pale ʻana i ka pale ʻana i nā poʻe i maʻi mua, e like me ka mea i hōʻike ʻia 21. Ma ka hoʻohālikelike ʻana, ʻo ka ikaika o ka SARS-CoV-2-specific IFN-γ T cell pane ʻo ia ka mea koʻikoʻi nui i ka hoʻoholo ʻana i nā kūʻokoʻa o ka hoʻāʻo ʻana i ka maikaʻi no COVID-19 (Figure 4f).ʻO ka holoʻokoʻa, ʻo nā mea komo me ka SARS-CoV-2-specific capillary T-cell pane ≤23.7 pg/mL IFN-γ he 14.9% ka hopena o ka maʻi i ʻekolu mahina i hoʻohālikelike ʻia me kahi pane> 141.6 pg/mL.ml IFN.-γ i loaʻa i ka maʻi o 4.4% (Pau 2).
IFN-γ+ T cell pane kikoʻī no SARS-CoV-2 (a; *P = 0.034) a me SARS-CoV-2 kikoʻī IgG-targeted receptor-binding domain (“RBD”) (b), spike subunit 1 (' S1′) (c), spike subunit 2 ('S2′) (d) and nucleocapsid binding reaction ('N') (e).Ua ʻike ʻia ka poʻe i komo i ka maikaʻi no nā hoʻokolohua COVID-19 (PCR a/a i ʻole ka hoʻāʻo ʻana i ke kahe koko lateral), ua loaʻa nā maʻi āpau i loko o 3 mau mahina ma hope o ka hoʻāʻo ʻana i ke koko.Hoʻohālikelike ʻia me ka hoʻohana ʻana i kahi hoʻokolohua Mann-Whitney ʻelua huelo.Hōʻike ʻia ka ʻikepili ma ke ʻano he kiʻi (laina waena ma waena, palena kiʻekiʻe ma 75th percentile, palena haʻahaʻa ma 25th percentile) me nā ʻumikū ma ka liʻiliʻi a me ka nui loa.Hōʻike kēlā me kēia kiko i kahi mea hāʻawi.ʻAʻole nui ka ns.Hōʻike ka wela wela f i ka hoʻopili ʻana o Spearman ma waena o nā mea hoʻololi no ka ʻikepili i kuhikuhi ʻia.Ua hoʻokaʻawale ʻia nā hoʻohālikelike ʻaʻole koʻikoʻi koʻikoʻi mai ka matrix a hōʻailona ʻia me nā cell blank.Hāʻawi ʻia ka ʻikepili maka ma ke ʻano o nā faila ʻike maka.
Ke neʻe nei mākou i ka pae aʻe o ka maʻi maʻi COVID-19, e neʻe ka manaʻo mai ka pale ʻana i ka hoʻokele pilikia pilikino a me ka ʻike ʻana i nā lālā palupalu o ke kaiāulu.ʻO ka hoʻokumu ʻana i nā correlates o ka pale ʻana i ka COVID-19 he mea koʻikoʻi ia e ʻike pono a mālama i kēia mau pūʻulu kiʻekiʻe.Ke hoʻonui nei nā hōʻike e pale ana ka T-cell immunity i ka maʻi SARS-CoV-2 a kaupalena i ka paʻakikī o COVID-1910.Hōʻike ka ʻikepili i hōʻike ʻia ma aneʻi ʻo ka hui pū ʻana o ka SARS-CoV-2-specific IFN-γ+ T cell pane e kūʻē i ka spike, membrane, a me ka nucleocapsid structural proteins e hāʻawi i ka pale ʻoi aku i ka COVID-19 ma mua o ka hoʻopaʻa ʻana o ka antibody. .a pono e noʻonoʻo ʻia i ka wā e loiloi ai i ka pale ʻana o ke kanaka a/a i ʻole nā holoholona.ʻO nā maʻi RNA e like me ka SARS-CoV-2 a i ʻole ka maʻi influenza A (IAV) e pale i ka neʻe ʻana o ka serological ma o ka hoʻomohala wikiwiki ʻana i nā epitopes B-cell i hōʻike ʻia ma luna o nā antigens i ʻike ʻia e nā antibodies.Hiki i ka pane pale pale i hāʻawi ʻia e nā pūnaewele T ke hōʻike i ka huli ʻana o nā epitopes mai nā wahi i mālama ʻia o nā protein viral ʻaʻole hiki ke pakele koke i kahi pane kūlohelohe.ʻO ka pale ʻana i ka cell-mediated T e kūʻē i ka moʻolelo SARS-CoV-2 ʻano like me ka heterosubtypic protection mediated by T cell targeting of conserved intrinsic proteins i ʻike ʻia ma IAV22,23 subtypes.
ʻOiai ka nui o ka mana no ke ana ʻana i ka pane ʻana o ka cellular immune i ka COVID-19, ua hāʻawi ʻia ka manaʻo liʻiliʻi i ka hoʻomohala ʻana i ka pololei, kiʻekiʻe-throughput, standardized T-cell assays.ʻO nā paʻakikī kuʻuna a me nā kumukūʻai e pili ana i ke ana ʻana i nā pane T cell e pale i ka hoʻoholo pololei ʻana o ka pale ʻana o ka cell T i ka wā e nānā ana no ka pale ʻana i ka lehulehu.ʻOiai ua loaʻa i kekahi mau ʻoihana hoʻoulu peptide koko holoʻokoʻa i loaʻa i kēia manawa, pono nā mea āpau i kēia manawa i kahi phlebotomist e kiʻi i ke koko, e kaupalena ana i ka loaʻa a me ka nui.Hoʻohana nui ʻia nā ʻōnaehana koko capillary e hoʻoholo ai i ka laha o nā antibodies SARS-CoV-2 i kahi heluna kanaka.Ua hoʻololi mākou i nā ho'āʻo koko capillary e hana i nā hōʻike hoʻoulu ʻana i ka peptide koko holoʻokoʻa e loiloi i ka hana ʻana o ka cell T i nā protein structural SARS-CoV-2 a me nā pane antibody kikoʻī SARS-CoV-2.ʻO ka ʻoiaʻiʻo, ʻo ke ana hui ʻana o nā antibodies SARS-CoV-2-specific a me nā keʻena T i ka laʻana koko capillary hoʻokahi he nani loa: (i) hoʻemi i ka pono o nā hoʻāʻo koko he nui i kēlā me kēia mea komo, (ii) hoʻomaikaʻi i ka ʻike a me ka ʻike o ka mea komo;(iii) hoʻomaikaʻi i ka logistic a hōʻemi i ka hana hou ʻana, (iv) hōʻemi i ka hopena o ke kaiapuni no ka mea ʻoi aku ka liʻiliʻi o nā mea hoʻohana hale keʻena a me ka hāʻawi ʻana i nā laʻana.ʻOiai ua like ka holoʻokoʻa IFN-γ reactivity ma waena o nā hōʻailona koko venous a me ka capillary, ua ʻike ʻia he haʻahaʻa i loko o ka cohort koko capillary o nā mea komo (Fig. 4a) i hoʻohālikelike ʻia me ka cohort venous blood (Fig. 2a).Nā waiwai IFN-γ He nui nā wehewehe no kēia ʻike, ʻo ia hoʻi, ka nui o nā poʻe i komo me nā comorbidities e koi ana i ka immunosuppressive therapy i kiʻi ʻia i loko o ka cohort sampling blood capillary (Table 1) a me Viability a / a i ʻole ka hana o nā cell T i loaʻa mai ka vascular. haʻahaʻa paha nā laʻana, ʻoi aku ka noʻonoʻo ʻana i nā kūlana o ka mālama lōʻihi o nā laʻana ma mua o ka hoʻoulu ʻana i ka peptide.
Hāʻawi ka lāʻau lapaʻau COVID-19 i kēia manawa i ka pale maikaʻi loa i ka maʻi koʻikoʻi no ka hapa nui o ka poʻe i loaʻa i loko o 6 mau mahina o ka hoʻopaʻa ʻana.ʻO ka hoʻoikaika ʻana, ʻoiai ka maikaʻi ʻole o ka serological neutralization o nā ʻano like ʻole o SARS-CoV-26,7, ʻo nā pane T-cell i hāpai ʻia e ka hoʻopaʻa ʻana e kūʻē i ke ʻano wild-type SARS-CoV-2 i hoʻomau nui ʻia, ʻoiai he 25 mau mea i puka mai.ʻO ka ʻikepili a mākou e hōʻike nei ma ʻaneʻi e hōʻike ana i ke koʻikoʻi o ka loiloi ākea o ka maʻi immunogenicity, e hōʻike ana i nā kano me ka lawa ʻole o ka T-cell e pale ai i ka maʻi hikiwawe a me ka hoʻomau mau ʻana o ka maʻi.Ua ʻike pū mākou he nui ka poʻe i hoʻopaʻa ʻole ʻia i hoʻopaʻa ʻia i loko o ka cohort capillary i pane koʻikoʻi o nā pūnana T kikoʻī SARS-CoV-2 (a me N-binding IgG) me ka ʻole o ka hoʻopaʻa ʻana ma mua, ʻo ia paha ma muli o ka maʻi ma mua.Ma mua o ka ho'opa'a 'ana i ka po'e kūpono, pono e loiloi 'ia ko lākou pilikia o ka ma'i ma muli o ko lākou kūlana lā'au lapa'au i kēia manawa a me nā koho i ho'omaopopo 'ia.
ʻO nā palena o kēia haʻawina e pili ana i ka hōʻoiaʻiʻo i hōʻike ʻia e nā poʻe komo i ka maʻi me SARS-CoV-2 ma hope o ka hōʻiliʻili koko e hoʻoholo ai i ka pili o ka palekana;loaʻa paha i kekahi poʻe i komo i ka maʻi asymptomatic a ʻaʻole hiki iā lākou ke hana i ka PCR a/a i ʻole ka hoʻāʻo ʻana i ka kahe lateral no COVID-19.Ua nele pū kā mākou ʻikepili i ka ʻike e pili ana i nā lāʻau lapaʻau o ka poʻe komo i ka manawa o ke koko.Eia kekahi, no ka hōʻike ʻana o kā mākou poʻe hui āpau i nā hōʻailona haʻahaʻa a i ʻole ʻaʻohe hōʻailona, ʻaʻole hiki ke ʻike i nā pane kūlohelohe mai kā mākou ʻikepili i wānana i ka piʻi nui ʻana o ka maʻi nui a me ka haukapila no COVID-19.Eia nō naʻe, ʻo ka loaʻa ʻana o nā pane cell CD8+ T e kūʻē i nā epitopes kikoʻī nucleocapsid i pili pū me ka pale ʻana i ka COVID-1926 koʻikoʻi.Eia kekahi, ʻo ka assay i hoʻohana ʻia ma aneʻi ʻaʻole i ana i nā pane T cell i hōʻike mua ʻia i nā protein non-structural SARS-CoV-2 i hōʻike ʻia i kēia manawa e hōʻiliʻili ʻia i nā limahana mālama olakino seronegative i hui pū me nā maʻi maʻi.Ma muli o kēia hana, hāʻawi ʻia i ka laha o ka hoʻouna ʻana i ke kaiāulu i ka manawa o ka hoʻopaʻa ʻana a me ke kiʻekiʻe o ka hoʻopili ʻana i ka maʻi i ka heluna kanaka, ʻike ʻia ka nui o nā cell T kikoʻī SARS-CoV-2 i loaʻa i kā mākou mau hoʻokolohua.nā maʻi subclinical i loko o kā mākou cohorts.ʻO ka mea hope loa, ʻaʻole mākou i ana i ka hana interleukin 2 e nā cell T no ka mea ua hōʻike kā mākou hana mua i ka ʻike maikaʻi ʻole o nā pane T-cell kikoʻī SARS-CoV-214, ʻoiai ʻo nā pane kikoʻī IL-2 e hōʻike i ka cross-reactivity mua.nā pūnaewele pili i ka pale ʻana i ka maʻi SARS-CoV-211.
Hoʻopili pū ʻia, hōʻike kēia mau ʻikepili i ka pono kumu no nā haʻawina lōʻihi lōʻihi e hoʻopili ana i nā pane cell T-Specific SARS-CoV-2 i nā ana o ka nui o ka lehulehu.Hiki ke kōkua ʻia kēia mau hana e ka hoʻomohala ʻana i kahi hoʻāʻo koko capillary hou e ana i ka pane T-cell.
Ua kiʻi ka papahana noiʻi i nā poʻe komo mai Pepeluali 2021 a Malaki 2022. ʻO ka hui o nā mea hāʻawi olakino (n = 148) nāna i hāʻawi i nā laʻana koko venous ka mea nui o nā limahana o ke kulanui a me nā haumāna e komo ana i ka lawelawe screening COVID-19 o Cardiff University a i ʻole nā limahana ma ke kula mua ma Cardiff.He olakino ʻē aʻe nā mea komo a ʻaʻole i hōʻike i ka lawe ʻana i nā lāʻau immunosuppressive (e nānā i ka Papa 1 no nā hiʻohiʻona).ʻO ka pūʻulu o nā poʻe i hāʻawi i nā laʻana koko capillary i loaʻa nā mea hāʻawi manawaleʻa āpau (18+ makahiki) mai kēlā ʻaoʻao o UK.Ma waena o Ianuali 24 a me Malaki 14, 2022, 342 i komo i loko o ke aʻo ʻana, a he 299 o lākou i waiho i nā laʻana koko i ka hale hana.He nui ka poʻe i komo i noho ʻole a hōʻike ʻia i nā maʻi maʻi koʻikoʻi, me nā maʻi autoimmune a me ka maʻi kanesa (e nānā i ka Papa 1 no nā hiʻohiʻona).Ua loaʻa kēia haʻawina i ka ʻae kūpono mai ka Newcastle and North Tyneside 2 Research Ethics Committee (ID IRAS: 294246) a me ka Cardiff University School of Medicine Research Ethics Committee (SREC ref: SMREC 21/01).Ua hāʻawi nā mea komo a pau i ka ʻae i kākau ʻia ma mua o ka hoʻokomo ʻana.ʻAʻole i loaʻa i ka poʻe i komo ka uku no ke komo ʻana i kēia haʻawina.
Ua loaʻa nā laʻana koko venipuncture i loko o 6 a i ʻole 10 ml lithium a i ʻole sodium heparin vacutainer (BD).Ua kiʻi ʻia nā laʻana koko capillary me ka manamana lima a ʻohi ʻia i loko o nā microcontainers heparin (BD).Pono ka liʻiliʻi o 400 µl o ke koko;e hōʻole ʻia kekahi laʻana ma lalo o kēia nui.ʻO nā kumu ʻē aʻe no ka hōʻole ʻana i ka laʻana, ʻo ia ka coagulation nui a / a hemolysis a me ka hiki ʻole ke hōʻiliʻili i ka plasma viscous no ka nānā ʻana (Supplementary Fig. 5).Loaʻa ka huina o 299 mau laʻana koko capillary no ka loiloi ʻana i nā pane antibody, a ʻo 270 nā laʻana i loaʻa pū no ka loiloi ʻana i nā pane o ka cell T.
Ua loiloi ʻia nā pane kikoʻī T cell SARS-CoV-2 me ka hoʻohana ʻana i ka COVID-19 Immuno-T assay (ImmunoServ Ltd) a hana ʻia e like me ka mea i wehewehe mua ʻia14.ʻO ka pōkole, ua lawe ʻia hoʻokahi 6 ml a i ʻole 10 ml sodium heparin (BD) venous vacutainer mai kēlā me kēia mea komo a hana ʻia i loko o ka hale hana i loko o 12 mau hola o ka hōʻiliʻili koko.ʻOiai ua hana ʻia ka hapa nui o nā specimens i loko o 24 mau hola, hoʻokahi 400-600 μl heparinized microbleeding (BD) koko capillary i hōʻiliʻili ʻia i loko o 48 mau hola o ka hoʻāʻo ʻana i ka manamana lima.Hoʻoulu ʻia nā laʻana koko Venous a/a i ʻole capillary me nā loko peptide ʻokoʻa i kikoʻī no SARS-CoV-2 (ʻano ʻano hihiu) e like me ka mea i wehewehe mua ʻia14.Aia kēia waihona peptide he 420 15-mer sequence me 11 overlapping amino acids e pili ana i ka spike protein (S1 a me S2) (S; NCBI protein: QHD43416 1), nucleocapsid phosphoprotein (NP; NCBI protein: QHD43423 2) a me ka membrane glycoprotein (M). ; NCBI protein: QHD43419 1) coding sequences (i kapa ʻia ʻo "S-/NP-/M-combinatorial peptide library").Hoʻomaʻemaʻeʻia nā peptides a pau i> 70%, hoʻoheheʻeʻia i loko o ka wai maʻemaʻe a hoʻohanaʻia i ka hopena hope loa o 0.5 μg / ml no ka peptide.Hoʻokomo ʻia nā laʻana ma 37 ° C no 20-24 mau hola.A laila ua centrifuged nā paipu ma 5000 × g no 3 mau minuke a ~ 150 µl o ka plasma i hōʻiliʻili ʻia mai ka piko o kēlā me kēia koko.E mālama i nā laʻana plasma ma -20°C no hoʻokahi mahina ma mua o ka holo ʻana i nā hoʻokolohua cytokine/antibody detection assays.
Ua ana ʻia ʻo IFN-γ me ka hoʻohana ʻana i ka IFN-γ ELISA MAX Deluxe Set (BioLegend, helu helu 430116) a hana ʻia e like me nā kuhikuhi a ka mea hana.Ma hope koke o ka hoʻohui ʻia ʻana o ka solution stop (2N H2SO4), ua heluhelu ʻia ka microplate ma 450 nm me ka hoʻohana ʻana i kahi mea heluhelu pākaukau BioLegend Mini ELISA.Ua helu ʻia ʻo IFN-γ e ka extrapolation curve maʻamau me ka GraphPad Prism.Ua hoʻopaʻa ʻia nā waiwai ma lalo o ka palena ʻike haʻahaʻa o ka assay e like me 7.8 pg / ml, nā waiwai ma luna o ka palena ʻike kiʻekiʻe o ka assay i hoʻopaʻa ʻia he 1000 pg / ml.
Ua ana ʻia nā antibodies Anti-SARS-CoV-2 RBD/S1/S2/N IgG me ka hoʻohana ʻana i kahi Bio-Plex Pro Human IgG SARS-CoV-2 4-plex panel (Bio-Rad, cat. no. 12014634) a ua hōʻailona ʻia e like me nā kuhikuhi a ka mea hana .kuhikuhi .Ua nānā hou ʻia nā helu hōʻike hōʻike ma luna o ka palena o ka quantitation ma kahi dilution 1:1000.Ua ana 'ia ka 'awelika o ka fluorescence o na pele ma kahi mea kani Bio-Plex 200 (Bio-Rad).Ua helu ʻia nā manaʻo antibody e ka VIROTROL SARS-CoV-2 single control assay (Bio-Rad) a hoʻololi ʻia i WHO/NIBSC 20/136 International Reference Standard Units (BAU/mL) me ka hoʻohana ʻana i ka mea calibration factor.
RBD a me S1 subunit-specific neutralizing antibodies e kūʻē i ka SARS-CoV-2 wild-type a me delta (B.1.617) ua ana ʻia nā laina SARS-CoV-2 me ka hoʻohana ʻana i ka Bio-Plex Pro Human SARS-CoV-2 Variant Neutralization Antibody Kit (Bio). -Rad, hapa helu 12016897), e like me nā ʻōlelo a ka mea hana.E ana i ka awelika o ka fluorescence ma ka Bio-Plex 200 (Bio-Rad) a e helu i ka pākēneka kaohi (ʻo ia hoʻi, neutralization) me ka hoʻohana ʻana i kēia ʻano:
Ua hana ʻia nā hoʻomaʻamaʻa ʻana i ka infectious neutralization no SARS-CoV-2 e like me ka mea i wehewehe mua ʻia28.ʻO ka pōkole, 600 PFU o nā ʻano ʻāhiu SARS-CoV-2 i hoʻopili ʻia me 3-fold serial dilutions o ka plasma i pālua no 1 hola ma 37 ° C.Hoʻohui ʻia ka hui ʻana i nā cell VeroE6 no 48 mau hola.Hoʻopaʻa ʻia nā monolayers me 4% paraformaldehyde, permeabilized me 0.5% NP-40 a hoʻomoʻa ʻia no 1 hola i ka pale pale (PBS i loaʻa ka 0.1% ma waena a me 3% skimmed waiū).Hoʻohui ʻia ka antibody primary (anti-nucleocapsid 1C7, Stratech) i ka pale ʻana i ka buffer no 1 hola ma ka lumi wela.Ma hope o ka holoi ʻana, ua hoʻohui ʻia kahi antibody lua (anti-mouse IgG-HRP, Pierce) i ka pale ʻana i ka buffer no 1 hola.Holoi ʻia nā monolayers, hoʻomohala ʻia me ka hoʻohana ʻana iā Sigmafast OPD a heluhelu ʻia ma kahi mea heluhelu papa Clariostar Omega.ʻO nā pūnāwai me ka maʻi ʻole, ʻaʻohe maʻi maʻi akā ʻaʻohe antibodies, a me ka sera maʻamau e hōʻike ana i ka hana waena i hoʻokomo ʻia i kēlā me kēia hoʻokolohua ma ke ʻano he mana.
Ua lawe ʻia ka ʻikepili helu ma GraphPad Prism (version 9.4.1).Ua ho'āʻoʻia ka maʻamau o ka hoʻonohonohoʻikepili me ka ho'āʻo Shapiro-Wilk.Ua hoʻohana ʻia nā pae hoʻohālikelike non-parametric no nā hoʻohālikelike āpau.Ua hoʻohana ʻia ka hoʻāʻo Mann-Whitney no nā laʻana i hoʻopaʻa ʻole ʻia.ʻO nā ho'āʻo a pau he ʻelua ʻaoʻao me ka paepae koʻikoʻi nominal o P ≤ 0.05.
Ua hana ʻia ka ʻimi ʻimi mua ʻana o ka ʻikepili ma R (version 4.0.3).Hoʻopili kēia i ka hoʻomohala ʻana i ka matrix univariate rank correlation matrix, kahi i hōʻike ʻia ai ka pilina ma waena o nā ʻano ʻelua e ka nui a me ke kala o nā ʻāpana.Ua helu ʻia ke koʻikoʻi helu ma waena o nā hui me ka hoʻohana ʻana i ka rho a Spearman, kahi i manaʻo nui ʻia nā waiwai ≤0.05.Ua hoʻokaʻawale ʻia nā hoʻohālikelike ʻaʻole koʻikoʻi koʻikoʻi mai ka matrix a hōʻailona ʻia me nā cell blank.Ua hoʻololi ʻia nā waiwai P no ka hoʻohālikelike ʻana me ka hoʻohana ʻana i ka hoʻoponopono ʻana a Holm.Ua hoʻohana ʻia kahi kumu hoʻohālikelike loiloi binary e hoʻohālikelike i ka hopena o nā ʻano like ʻole i ka ʻikepili i ka pane maikaʻi i ka COVID-19.IFN-γ T cell pane a me anti-RBD/S1/S2/N IgG titer scores ua hoʻololi ʻia i mau kumu, kahi i hāʻawi ʻia ai kēlā me kēia kanaka i ka quartile kūpono no kēlā me kēia helu.Ma hope o ia mea, ua hoʻomohala ʻia kahi ʻano noiʻi mua me ka hoʻohana ʻana i ka hana glm i loko o ka pūʻolo helu helu (V4.0.3).Ua unuhi ʻia nā ratio like ʻole i loaʻa mai kēia kumu hoʻohālike kumu mai nā coefficients o ke kŘkohu me ka hoʻohana ʻana i ka hana 'odds_plot' i loko o ka pūʻolo OddsPlotty (V1.0.2).I ka hoʻomohala ʻana i ke kumu hoʻohālike cross-validation, ua hoʻohana mākou i ka hana "bestglm" mai ka pūʻolo bestglm (V0.37.3) e kaupalena i ka manaʻo o ka mea hoʻohana a hōʻoia i ka hiki ke koho ʻia ka ʻāpana maikaʻi loa o nā wānana.ʻO ke ʻano i koho ʻia he "pau" a ʻo ka ʻike ʻike i hoʻohana ʻia no ka loiloi ʻana i ke kūpono o ka hoʻohālike ʻo AIC.Ua hoʻohana ʻia ke kaʻina hana like i hōʻike ʻia ma luna no ka loaʻa ʻana o ka ratio odds.
No ka ʻike hou aku e pili ana i ka hoʻolālā haʻawina, e ʻike i ka abstract study Nature i hoʻopili ʻia i kēia ʻatikala.
Pono e hoʻouna ʻia nā leka a me nā noi no ke kauka iā Kauka Martin Scarr a i ʻole Professor Andrew Godkin.Hāʻawi kēia ʻatikala i ka ʻikepili kumu.
Loaʻa i ka lehulehu ka code R i hoʻohana ʻia no ka hana ʻana i nā kumu hoʻohālike me ka noi ʻole29.Hiki ke loaʻa ka ʻike hou a me nā laikini ma www.nature.com/reprints.
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Ka manawa hoʻouna: Feb-25-2023