Pre-existing T-cell Immunity To SARS-CoV-2 in Unexposed Healthy Controls in Ecuador, As Kuaj Nrog Tus Kab Mob Khaus Viv -19 Interferon-Gamma Release Assay

TSAB NTAWV

Keeb Kwm: Kev tshawb fawb ntawm T-cell tiv thaiv kab mob tiv thaiv SARS-CoV-2 yog qhov tseem ceeb hauv kev nkag siab txog kev tiv thaiv kab mob ntawm tib neeg lossis pej xeem. Ntawm no, peb siv ib qho yooj yim, pheej yig, thiab ceev tag nrho cov ntshav stimulation assay - Interferon-Gamma Release Assay (IGRA) - los kawm T-cell tiv thaiv kab mob rau SARS-CoV-2 hauv convalescent COVID-19 cov neeg mob thiab kev sib cuag tsis zoo los ntawm Quito, Ecuador. Txoj kev: Interferon-gamma (INF-g) ntau lawm tau ntsuas nyob rau hauv cov ntshav heparinized ntawm convalescent thiab unexposed cov ntsiab lus tom qab stimulation rau 24 teev nrog SARS-CoV-2 Spike S1 protein, Receptor Binding Domain (RBD) protein los yog Nucleocapsid (NP) protein, feem. Lub xub ntiag ntawm IgG-RBD cov tshuaj tiv thaiv protein nyob hauv ob pawg kev tshawb fawb tau txiav txim siab nrog "hauv tsev" ELISA. Cov txiaj ntsig: Raws li ntsuas nrog INF-g ntau lawm, 80 feem pua ​​​​ntawm cov neeg mob uas muaj tus kab mob COVID-19, tag nrho cov IgG-RBD seropositive, muaj T-cell teb.

Txawm li cas los xij, xav tsis thoob, 44 feem pua ​​​​ntawm cov kev tswj tsis tau noj qab haus huv, tag nrho IgG-RBD seronegative, muaj cov kab mob tshwj xeeb tshwj xeeb T-cell teb nrog COVID-19 IGRA, tej zaum yog vim ua ntej raug mob khaub thuas ua rau mob coronaviruses lossis lwm yam. kab mob los yog microbial antigens. Xaus thiab Kev Sib Tham: Qhov feem pua ​​​​ntawm cov kev noj qab haus huv tsis tau nthuav tawm nrog kev tiv thaiv yav dhau los qhia tias ib feem ntawm cov neeg Ecuadorian yuav muaj SARS-CoV-2 reactive T-cells. Muab hais tias cov txheej txheem IGRA yog qhov yooj yim thiab tuaj yeem ntsuas tau yooj yim rau kev tshawb nrhiav qhov twg cov neeg mob xav tau ntau, qhov COVID-19 IGRA tuaj yeem ua haujlwm los txiav txim seb T-cell-tsuas teb yog sawv cev tiv thaiv kev tiv thaiv rau SARS-CoV. -2 kab mob hauv kev tshawb fawb txog pej xeem. © 2021 Tus Sau. Tshaj tawm los ntawm Elsevier Ltd sawv cev ntawm International Society for Infectious Diseases.

Nyob rau tib lub sijhawm, thaum peb kev tiv thaiv qis, muaj ntau txoj hauv kev los txhim kho kev tiv thaiv kab mob, noj cov zaub mov uas tuaj yeem txhim kho kev tiv thaiv kab mob, xws li cistanche, polysaccharides, proteins, amino acids, thiab lwm yam khoom muaj nyob hauv cistanche feem ntau tuaj yeem tswj hwm lub cev.ilub cev.

Nyem cistanche tubulosa extract hmoov khoom

Taw qhia

Kev tiv thaiv kab mob tiv thaiv kab mob SARS-CoV-2 tsis yog tsuas yog tsim cov tshuaj tiv thaiv kab mob xwb, tab sis tus kab mob kuj ua rau T-cell teb rau cov neeg mob (Lipsitch li al., 2020, Ni et al., 2020). Feem ntau, kev txiav txim siab txog qhov muaj thiab qhov loj ntawm lub cim xeeb tshwj xeeb T-cell teb rau tus kab mob coronavirus no tau ua nrog ELISPOT kev soj ntsuam los ntawm kev tsim cov lej ntawm cov lymphocytes uas tsim IFN-g tom qab stimulation nrog cov kab mob tshwj xeeb antigens lossis peptides (Ni et al., 2020, Pai et al., 2014, Abate et al., 2013, Braun et al., 2020, Grifono et al., 2020, LeBert et al., 2020, Sekine et al., 2020).

Rau cov txheej txheem no, peripheral ntshav mononuclear hlwb (PBMCs) raug cais tawm los ntawm cov ntshav heparinized tshiab los ntawm kev ceev-gradient centrifugation; Kev tso tawm ntawm cytokines los ntawm ib tus neeg T-hlwb yog ntsuas los ntawm lub tshuab tsom iav lossis nrog lub cuab yeej tshwj xeeb - ELISPOT phaj nyeem ntawv. ELISPOT assay yog ib qho "rau kev tshawb fawb lub chaw soj nstuam nkaus xwb" cov txheej txheem uas ua haujlwm hnyav, kev xav tau, tus nqi kim, thiab tsis tuaj yeem siv tau yooj yim hauv chav kuaj mob lossis siv hauv kev tshawb fawb pej xeem. Vim yog tus nqi, kev tsim kho vaj tse, thiab chaw kuaj mob xav tau los ua qhov kev ntsuam xyuas, nws siv hauv cov peev txheej txwv xws li Ecuador tej zaum yuav tsawg.

Cov tshuaj tiv thaiv kab mob hauv lub cev kuj tuaj yeem txiav txim siab nrog qhov kev ntsuam xyuas yooj yim dua: kev ntsuam xyuas interferon-gamma tso tawm (IGRA). Qhov kev ntsuam xyuas no, kev kuaj ntshav hauv vitro, ntsuas T-cell secreted cytokines (piv txwv li, gamma interferon (IFN-g); Txawm li cas los xij, lwm cov cytokines xws li TNF lossis IL-2 kuj tuaj yeem ntsuas kom muaj nuj nqis) raws li kev txhawb nqa ntawm tag nrho cov ntshav. (tsis yog cov lymphocytes cais) nrog cov antigens tshwj xeeb (Pai li al., 2014, Abate li al., 2013). Cov cytokine zais cia IFN-g yog ntsuas nrog ELISA kev soj ntsuam, cov txheej txheem yooj yim muaj nyob hauv ntau lub chaw kuaj mob, thiab cov txiaj ntsig tau nyeem nrog ELISA phaj nyeem. IGRAs tau pom ib daim ntawv thov nyob rau hauv lub chaw soj ntsuam kuaj mob thiab yog siv los txiav txim tus kab mob latent nrog Mycobacterium tuberculosis (MTB) nrog rau ntsuas cytomegalovirus (CMV) - tshwj xeeb cell-mediated tiv thaiv kab mob thiab kwv yees tus kab mob CMV hauv cov neeg tau txais kev hloov pauv (Pai li al. , 2014, Abate et al., 2013). Cov kev xeem IGRA no tau raug soj ntsuam ntau thiab, piv nrog ELISPOT qhov kev xeem, tau pom tias muaj peev xwm zoo sib xws rau kev kwv yees MTB lossis CMV kab mob. Tsis tas li ntawd, ntau qhov kev lag luam thiab FDA lossis CE-kos tshuaj ntsuam xyuas kev tiv thaiv kab mob TB lossis CMV muaj thiab tau ua tiav.

Hauv txoj kev tshawb fawb tam sim no, peb tshawb nrhiav kev siv COVID-19 IGRA thiab ntsuas qhov loj ntawm IFN-g tso tawm hauv cov neeg mob uas muaj tus kab mob COVID-19 thiab kev noj qab haus huv COVID-19 kev tswj hwm tsis zoo hauv kev teb rau cov lus tshwj xeeb antigens of the SARS-CoV-2 virus: the RBD protein; S1 ib feem ntawm Spike protein; los yog Nucleocapsid (N) protein. Tsis tas li ntawd, peb txiav txim siab qhov muaj SARS-CoV-2 cov tshuaj tiv thaiv IgG tshwj xeeb hauv cov neeg koom nrog "hauv tsev" ELISA (Amanat et al., 2020, Guevara et al., 2021). Peb qhia tau tias feem pua ​​​​ntawm cov neeg pub dawb uas tsis tau pom dua muaj SARS-CoV-2 reactive T-cells, thiab peb tham txog cov txiaj ntsig no.

Khoom siv thiab cov txheej txheem

Convalescent COVID-19 cov neeg mob, tswj kev noj qab haus huv, thiab kev teeb tsa

Txoj kev tshawb no tau ua nyob rau hauv Quito, Ecuador, thaum lub Cuaj Hli 2020. Tsis muaj cov txheej txheem txheeb cais tau siv los txiav txim siab tus qauv loj. Daim duab 1 qhia txog tus yam ntxwv ntawm 32 tus neeg mob hauv txoj kev tshawb no: kaum peb tus neeg mob COVID-19 tus neeg mob, txhua tus uas tsis muaj tus mob COVID-19 cov tsos mob/cov tsos mob thiab kev kuaj mob RT-PCR zoo nyob rau lub Rau Hli 2020; thiab 17 qhov kev tswj tsis tau zoo. Cov kev tswj hwm kev noj qab haus huv no tau ceev faj heev thaum muaj kev sib kis, zam kev sib cuag nrog lwm tus neeg, thiab nws tus kheej tau tshaj tawm tsis muaj cov tsos mob thiab cov tsos mob ntawm COVID-19 rau lub sijhawm muaj tus kabmob kis, xws li ua npaws, hnoos tsis tu ncua, los yog tsis hnov ​​tsw los yog saj. Tsis tas li, ob tus neeg nqa khoom asymptomatic SARS-CoV-2 tau suav nrog hauv txoj kev tshawb no. Ob qhov kev kawm no yeej tsis pom muaj cov tsos mob lossis cov tsos mob ntawm COVID-19 kab mob; Txawm li cas los xij, cov txheej txheem RT-PCR tau ua tiav rau lawv raws li qhov yuav tsum tau ua rau daim ntawv tso cai ua haujlwm thaum Lub Rau Hli 2020 thiab ua rau muaj kev kuaj mob zoo.

Serology

Serology thiab IGRAs rau txhua tus neeg mob thiab kev tswj hwm tau ua nyob rau ob lub lis piam dhau los ntawm lub Cuaj Hli 2020, peb lub hlis tom qab kuaj RT-PCR ntawm cov neeg mob convalescent. Txhawm rau txiav txim siab qhov muaj tus kabmob coronavirus tshwj xeeb IgG cov tshuaj tiv thaiv hauv peb pawg kawm, ib qho "hauv-tsev" SARS-CoV-2 Receptor Binding Domain (RBD) IgG ELISA (9, 10) tau siv.

Interferon Gamma Release Assay (IGRA)

Rau IGRA, ib qho kev kuaj ntshav heparinized (4 mL) thiab muab faib ua aliquots ntawm 250 mL thiab txhawb nqa nrog 2 mg / mL ntawm RBD protein (txoj kev cais tawm los ntawm kev siv 9) lossis 2 mg / mL ntawm cov khoom lag luam muaj Nucleocapsid. (N) protein los yog Spike (S1) protein (ViroGen, Catalog Numbers: 00,221-V thiab 00,226-V feem). Ib koob tshuaj tiv thaiv kab mob teb nrog ntshav los ntawm IGRA-zoo thiab IGRA-tsis zoo cov neeg mob tau siv los txiav txim siab cov antigens qhov zoo tshaj plaws concentration rau stimulation hauv IGRA. Ntawm 2 ug/mL, qhov siab tshaj plaws IFN-g cov lus teb hauv cov ntshav los ntawm COVID{15}} cov ntsiab lus tau pom yam tsis muaj kev txhawb nqa hauv cov kev tswj tsis muaj kab mob. Rau txhua tus neeg koom nrog, kev tswj tsis tau (NIL) tau suav nrog, thiab peb tau soj ntsuam 250 mL cov ntshav kuaj nrog mitogen phytohaemagglutinin (PHA), kev tswj zoo los ntsuas cov cytokine teb tus nqi ntawm cov qauv ntshav. Kev txhawb zog tau pom zoo nyob rau hauv 96-zoo tiaj-hauv qab ELISA phaj ntawm 37 C rau 24 teev. Plasma tau sau tseg, thiab IFN-g ntau lawm tau txiav txim siab nrog tib neeg IFN-g ELISA (MaxTM Standard Set Biolegend miv. No. 430,101).

Cov txiaj ntsig

RBD IgG ELISA tau qhia tias txhua tus neeg mob COVID{{0}} cov tsos mob (RT-PCR zoo) tau zoo rau cov tshuaj tiv thaiv IgG tiv thaiv RBD protein peb lub hlis tom qab kuaj RT-PCR. Ob tus neeg mob asymptomatic RT-PCR zoo thiab tag nrho cov neeg mob uas tsis muaj kev tswj hwm kev noj qab haus huv tau ua rau muaj kev cuam tshuam nrog ELISA (Saib Daim duab 1). Cov txiaj ntsig ntawm tag nrho cov ntshav stimulation hauv COVID-19 IGRA assay yog qhia nyob rau hauv daim duab 1. Muaj zog induction ntawm IFN-g ntau lawm tau pom nyob rau hauv 80 feem pua ​​​​ntawm COVID-19 cov tsos mob ntawm cov neeg mob nrog tag nrho peb cov antigens, tab sis cov N protein thiab S protein yog cov muaj zog tshaj stimulators ntawm IFN-g teb (Daim duab 1 A, B, C). Ob tus neeg mob asymptomatic tab sis RT-PCR-zoo (cov neeg mob 14 thiab 15), ob qho tib si tsis muaj SAR-CoV-2 cov tshuaj tiv thaiv kab mob, kuj tau pom qhov muaj zog tiv thaiv T-cell tsis muaj zog. Ntawm COVID{19}} cov neeg mob tsis zoo, 45 feem pua ​​​​pom tias tsis muaj T-cell tiv thaiv kab mob. Cov lus teb nyob rau hauv cov kev tswj tsis tau noj qab haus huv no nrog cov lus teb T-cell yog qhov ntsuas tsis sib txawv hauv qhov loj ntawm cov neeg mob convalescent COVID-19 rau ib qho ntawm cov stimulating antigens (p-value=0.271, 0.437, thiab 0.719 rau RBD, N, thiab S1 proteins, ntsig txog).

Daim duab 1. IFN-g ntau lawm tom qab stimulating tag nrho cov ntshav ntawm convalescent COVID-19 cov neeg mob thiab noj qab haus huv unexposed tswj nrog RBD, N, los yog S1 protein.

Cov txiaj ntsig ntawm kev txhawb nqa ntawm cov neeg mob convalescent thiab tswj nrog, raws li, RBD, N, lossis S1 protein tau qhia hauv daim duab 1A, B, thiab C. Hauv daim duab 1D, INF-g cov lus teb ntawm txhua tus neeg mob thiab rau peb. antigens yog pawg. Cov neeg mob uas tau lees paub tus kab mob COVID-19 yog tus lej 1–15, ntawm cov neeg mob 14 thiab 15 yog asymptomatic. Yam 16–33 yog COVID{11}} cov neeg mob tsis zoo.

Tom qab 24 teev ntawm stimulation, IFN-g concentrations hauv plasma tau txiav txim siab siv cov khoom lag luam uas muaj tib neeg IFN-g enzyme-linked immunosorbent assay-based kit (Biolegend cat. No. 430,101). Qhov loj ntawm qhov stimulation tau nthuav tawm raws li qhov pom kev ntom ntom ntawm 450 nm (OD450) rau cov ntshav txhawb nrog antigen rho tawm OD450 rau cov ntshav tsis muaj antigen stimulation. Ib qho OD ntawm 1.0 sib npaug nrog kwv yees li 400 pg / mL IFN-g. Phytohemagglutinin (PHA) tau siv los ua cov mitogen ntawm qhov kawg ntawm 5 mg / mL hauv IGRA los ntsuas qhov ua tau zoo thiab lub peev xwm teb ntawm cov ntshav. Txhua tus neeg mob thiab kev tswj hwm tau pom tias muaj kev tsim ntau tshaj plaws ntawm cytokine nrog cov mitogen no nrog qhov nruab nrab ntawm qhov muag pom (OD450) ntawm 2.54 (SD=0.13), sawv cev kwv yees li 1000 pg / mL ntawm IFN-g. Tsis muaj qhov sib txawv ntawm qhov nruab nrab IFN-g qib hauv cov ntshav tsis muaj zog ntawm cov neeg mob convalescent thiab tswj kev noj qab haus huv (OD450=0.38, SD=0.14 piv rau OD450=0.32. SD=0.16). Cov txiaj ntsig no tsis tshwm sim. Ib kab kab rov tav tau kos rau hauv txhua daim duab los sawv cev tus nqi txiav tawm rau kev txhawb nqa. Qhov txiaj ntsig no tau txiav txim siab los ntawm kev suav qhov nruab nrab ntxiv rau ob tus qauv sib txawv ntawm cov lus teb ntawm cuaj yam kev kawm (cov neeg mob 16, 18, 19, 22, 27-31) ntawm pawg tswj hwm nrog qis tshaj INF-g ntau lawm tom qab stimulation.

Kev sib tham thiab xaus

Siv ib qho yooj yim-rau-ua tag nrho cov ntshav ntsuam xyuas uas ntsuas T-cell cov lus teb, peb pom tias feem ntau convalescent cov neeg mob thiab ib tug tseem ceeb feem ntawm cov neeg noj qab haus huv unexposed cov neeg muaj ib tug tshwj xeeb thiab muaj zog T-cell teb txiav txim nrog rau zus tau tej cov INF-g tom qab stimulation. with SARS-CoV-2 specific antigens (Figure 1). Ntau qhov kev tshawb fawb, tag nrho siv ELISPOT qhov kev ntsuam xyuas, tau tshaj tawm tias muaj T-cell teb nyob rau hauv feem ntau lossis tag nrho cov neeg mob uas muaj tus kab mob COVID-19 (Braun li al., 2020, Grifono et al., 2020, LeBert li al. , 2020, Sekine et al., 2020, Moderbacher et al., 2020, Mateus et al., 2020, Peng et al., 2020).

Txawm li cas los xij, hais txog T-cell cov lus teb hauv kev noj qab haus huv tsis raug tswj hwm, cov lus teb ntawm 28 thiab 50 feem pua ​​​​tau tshaj tawm (Doshi, 2020, de Vries, 2020, Lipsitch li al., 2020, Sagar et al., 2020), thiab ntau yam. cov kev tshawb fawb qhia tsis muaj T-cell teb hauv COVID-19 cov neeg mob tswj tsis tau (de Vries, 2020, Moderbacher li al., 2020, Schwarzkopf et al., 2021). Feem ntau ntawm cov kev tshawb fawb no tau ua nrog ELISPOT assay, tab sis hauv Ltalis thiab Asmeskas, ib qho IGRA kuj tau siv los kuaj tus kab mob SARS-CoV-2 T-cell teb (Petrone li al., 2020, Murugesan li al. ., 2020). Hauv ob qho kev tshawb fawb, cov lus teb tshwj xeeb T-cell raug kuaj pom hauv cov neeg mob convalescent; Txawm li cas los xij, IGRA tsis pom qhov INF-g cov lus teb hauv cov ntsiab lus noj qab haus huv uas tsis pom zoo.

Pre-existing T-cell immunity to SARS-CoV-2 in COVID-19 cov ntsiab lus tsis zoo tau raug tshuaj xyuas hauv ntau qhov kev tshaj tawm (Altmann thiab Boyton, 2020, Dosho et al., 2020, de Vries, 2020, Sette thiab Crotty, 2020). Yog vim li cas vim li cas ib qho tshwj xeeb COVID-19 T-cell teb tej zaum yuav raug kuaj pom nyob rau hauv ib qho kev noj qab haus huv uas tsis tau nthuav tawm tseem tsis tau paub meej thiab yog qhov kev xav tau. Feem ntau ELISPOT cov kev tshawb fawb nrog COVID{11}} cov ntsiab lus tsis zoo siv tib neeg cov ntshav kuaj tau los ua ntej tus kab mob SARS-CoV-2 tau tshawb pom xyoo 2019, yog li ua ntej muaj feem kis tau. Vim li no, cov kev tshawb fawb ELISPOT tau txiav txim siab tias T-cell cov lus teb hauv cov ntsiab lus noj qab haus huv tsis tuaj yeem los ntawm kev sib cuag ua ntej nrog kev sib kis "mob khaub thuas" coronaviruses (Grifoni li al., 2020, Matheus et al., 2020) lossis yav dhau los raug khaub thuas. thiab/lossis CMV kab mob (Mahajan li al., 2020) los yog lwm yam kab mob los yog microbial antigens (Tan li al., 2020). Peb txoj kev tshawb fawb tau siv cov ntshav coj mus rau lub sijhawm muaj tus kabmob kis thoob ntiaj teb los ntawm cov neeg tuaj yeem pab dawb uas nws tus kheej tau tshaj tawm xoom kev sib cuag, yog qhov ua rau tus kabmob COVID-19 antigen RBD, thiab tsis tau pom muaj cov tsos mob lossis cov tsos mob ntawm COVID-19.

Yog li peb tsis tuaj yeem cais tawm tias T-cell cov lus teb hauv qee qhov ntawm peb qhov kev tiv thaiv COVID-19 "naïve" kev noj qab haus huv los ntawm asymptomatic SARS-CoV-2 kab mob. Cov neeg mob 14 thiab 15 ntawm peb txoj kev tshawb fawb yog ib qho piv txwv ntawm qhov no. Cov tib neeg no tau raug cais raws li COVID-19 cov neeg mob vim muaj RT-PCR zoo; Txawm li cas los xij, lawv tau asymptomatic thiab tsis tau tsim cov tshuaj tiv thaiv kab mob tiv thaiv RBD protein, tab sis ob qho tib si pom muaj T-cell teb.

Nws muaj peev xwm hais tias, tom qab SARS-CoV-2 colonization ntawm nasopharynx, lub cev tsis muaj zog ntawm ob tus neeg mob asymptomatic no tau tso lawv nrog lub cim xeeb Tcells nkaus xwb, thiab tsis muaj SARS-CoV-2 cov tshuaj tiv thaiv tshwj xeeb tau induced. Lwm qhov kev piav qhia yog tias T-cell teb los ntawm kev kis tus kab mob zoo li corona yav dhau los, thiab T-cell tiv thaiv kab mob ua ntej tau tiv thaiv ob tus neeg mob no tiv thaiv kev txhim kho ntawm tus kab mob ntau dua. Cov kab mob sib kis ua ntej T-hlwb tuaj yeem yog qhov tseem ceeb hauv kev piav qhia qee qhov sib txawv ntawm tus kab mob lossis kab mob (Le Bert li al., 2020, Sagar et al., 2020). Hais txog pawg tswj hwm tsis zoo, peb tsis suav nrog cov pab pawg no muaj ntau tus lej ntawm SARSCoV-2 cov neeg muaj tus kabmob uas tsis pom muaj tus kabmob asymptomatic, feem ntau vim tias tag nrho cov kev sib koom ua ke ntawm pawg tswj hwm yog IgG seronegative rau RBD antigen.

Lwm qhov laj thawj yog tias tus kab mob kis tau zoo hauv Ecuador kuj tsawg. Thaum lub sijhawm kawm no, thaum lub Cuaj Hlis 2020, Ecuador tau tshaj tawm txog 200,000 lees paub COVID-19 tus neeg mob (kwv yees li 1.1 feem pua ​​​​ntawm cov pej xeem). Tau kawg, qhov tseeb kis kab mob tuaj yeem ua rau ntau zaus ntau dua, tab sis txawm li ntawd los, nws tsis tsim nyog tias 45 feem pua ​​​​ntawm pab pawg tswj hwm no tau kis tus kab mob, thiab yog li peb tab tom saib T-cell teb tshwj xeeb rau SARS-CoV{ {9}} kab mob.

Hauv kev xaus, kev tshawb pom ntawm feem pua ​​​​ntawm cov neeg noj qab haus huv uas tsis muaj kev tiv thaiv yav dhau los hauv Quito, Ecuador, ua rau muaj kev cia siab tias ib feem tseem ceeb ntawm peb cov pej xeem yuav muaj SARS-CoV-2 reactive T-cells vim ntawm kev kis tus kab mob khaub thuas ua ntej, kab mob CMV, lossis kab mob khaub thuas ua rau mob khaub thuas. Cov kev tshawb fawb yav tom ntej yuav tsum tsom los txiav txim seb puas muaj cov tshuaj tiv thaiv kab mob uas twb muaj lawm tiv thaiv thiab/lossis tuaj yeem kov yeej tus kab mob COVID-19 hnyav dua lossis pab txhawb kom rov zoo dua.

Qhov tseem ceeb thiab kev txwv ntawm txoj kev tshawb no

Peb txoj kev tshawb fawb tau pom tias COVID-19 IGRA yog ib qho tseem ceeb thiab cov cuab yeej tshiab uas muaj txiaj ntsig zoo uas tuaj yeem ntsuas qhov kis tus kabmob coronaviruses lossis cuam tshuam rau cov kab mob zoo sib xws los ntawm kev txiav txim siab tso tawm IFN-g tom qab kev txhawb nqa nrog cov kab mob tshwj xeeb antigens. Cov txheej txheem yog yooj yim, kuj pheej yig, thiab tuaj yeem siv hauv chav kuaj mob. Qhov no yeej tsis yog qhov teeb meem nrog ELISPOT kev soj ntsuam. Tsis tas li ntawd, IGRA qhov kev ntsuam xyuas tuaj yeem ntsuas tau yooj yim rau cov kev tshawb fawb pej xeem thiab kev tshawb nrhiav qhov twg cov neeg mob xav tau ntau. Ua ke nrog serology, IGRA tuaj yeem siv los tshuaj xyuas ob qho tib si tshuaj tiv thaiv kab mob thiab T-cell cov lus teb ntawm tus neeg mob kom nkag siab zoo dua cov pej xeem-theem tiv thaiv kab mob thiab txiav txim siab kev tiv thaiv yav dhau los hauv cov tib neeg seronegative.

Ib qho kev txwv tseem ceeb ntawm peb txoj kev tshawb fawb yog tias cov qauv kev tshawb fawb tsis yog sawv cev ntawm cov pej xeem. Tsis muaj cov txheej txheem txheeb cais tau siv los txiav txim siab tus qauv loj. Tsis tas li ntawd, peb qhov kev ntsuam xyuas tsis txawv ntawm IFN-g ntau lawm ntawm CD4 ntxiv lossis CD8 ntxiv cov hlwb, tab sis kev txhawb nqa nrog CD8 (ntxiv) thiab CD4 (ntxiv) peptides tuaj yeem txiav txim siab (Grifoni li al., 2020, Peng li al. , 2020) thiab tau siv hauv IGRAs tau piav qhia hauv Petrone li al., 2020 thiab Murugesan li al., 2020). Tsis tas li, qhov induction ntawm lwm cov cytokines tuaj yeem ntsuas nrog IGRA no (Petrone li al., 2020). Ib yam li ntawd, IGRA tuaj yeem ua haujlwm rau kev ua raws li kev txhaj tshuaj tiv thaiv los txiav txim siab txog kev txhim kho T-cell cov lus teb hauv cov neeg tau txhaj tshuaj lossis tuaj yeem siv los txiav txim siab seb puas muaj cov tshuaj tiv thaiv kab mob sib kis tau cuam tshuam nrog kev tiv thaiv kev tiv thaiv thiab tuaj yeem siv los txiav txim siab seb puas muaj cov tshuaj tiv thaiv kab mob sib kis. txo qis tus kab mob tshwm sim los ntawm tus kab mob SARS-CoV-2 (Sagar et al., 2020).

Kev pom zoo ntawm Ethics thiab kev tso cai koom nrog

Cov ntshav tau sau tseg raws li kev pom zoo sau tseg. Pawg Neeg Saib Xyuas Kev Ncaj Ncees ntawm Lub Tsev Haujlwm Saib Xyuas Kev Noj Qab Haus Huv ntawm Ecuador tau pom zoo txoj cai kawm 004-2020.

Kev tsis sib haum xeeb

Cov kws sau ntawv tshaj tawm tias lawv tsis muaj kev sib tw nyiam.

Sau cov nyiaj pab

Kawm tsim; JHW thiab GE; Kev sau cov ntaub ntawv thiab kev sim kuaj: GE, AG, JC, AMR, thiab MMV; Kev txheeb xyuas cov ntaub ntawv; JHW, GE, thiab ET; Sau: JHW, GE, thiab ET.

Kev lees paub

Peb ua tsaug rau txhua tus neeg pub dawb thiab cov neeg saib xyuas kev noj qab haus huv koom nrog hauv txoj haujlwm no, tshwj xeeb tshaj yog Sandra Vivero thiab Sandra Fonseca, rau kev pab hauv kev sau cov qauv. Txoj kev tshawb no tau txhawb nqa los ntawm kev tshawb fawb los ntawm Universidad de las Américas. Lub koom haum Sustainable Sciences, San Francisco, California, Tebchaws Asmeskas, thiab "Por Todos" Foundation hauv Ecuador tau muab cov protein RBD thiab "hauv tsev" ELISA. Ua tsaug rau Howard E. Takiff thiab Flor Pujol (IVIC, Venezuela), Paulina E. Andrade (USFQ, Ecuador), thiab Lilly Verhagen (UMC, Netherlands) rau lawv cov kev sib tham muaj txiaj ntsig.

Cov ntaub ntawv

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Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, et al. SARS-CoV-2- kev tiv thaiv Tcell tshwj xeeb hauv cov xwm txheej ntawm COVID-19 thiab SARS, thiab kev tswj tsis tau kis. Xwm Txheej 2020;584(7821):457–62.

Lipsitch M, Grad YH, Sette A, Crotty S. Cross-reactive memory T cells thiab herd immunity to SARS-CoV-2. Nat Rev Immunol 2020.

Mahajan S, Kode V, Bhojak K, Magdalene CM, Lee K, Manoharan M, et al. Immunodominant T-cell epitopes los ntawm SARS-CoV-2 spike antigen qhia qhov muaj zog tiv thaiv T-cell uas muaj nyob rau hauv cov tib neeg uas tsis tau nthuav tawm. bioRxiv 2020.

Mateus J, Grifoni A, Tarke A, Sidney J, Ramirez SI, Dan JM, et al. Selective and crossreactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 2020; 370 (6512): 89–94.

Moderbacher RC, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 thiab koom nrog hnub nyoog thiab kab mob hnyav. Cell 2020; S0092-8674(20):31235–6.

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Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, et al. Kev kuaj pom ntawm SARS-CoV-2- tshwj xeeb humoral thiab cellular tiv thaiv kab mob hauv COVID-19 cov neeg uas tsis muaj hnub nyoog. Kev tiv thaiv kab mob 2020;52(6)971–7.

Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon tso tawm kev soj ntsuam rau kev kuaj pom tus kab mob Mycobacterium tuberculosis. Clin Microbiol Rev 2014; 27(1:3–20.

Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z, Dong D, et al. Kev nco dav dav thiab muaj zog CD4 ntxiv thiab CD8 ntxiv rau T hlwb raug ntxias los ntawm SARS-CoV-2 hauv UK cov neeg mob rov qab los ntawm COVID-19. NatImmunol 2020.

Petrone L, Petruccioli E, Vanini V, Cuzzi G, Fard SN, Alonzi T, et al. Kev kuaj ntshav tag nrho los ntsuas SARS-CoV-2- cov lus teb tshwj xeeb hauv cov neeg mob COVID-19. Clin Microbiol Infect 2020.

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