SARS-CoV-2 Variants Resistant To Monoclonal Antibodies in Immunocompromised Patients Constitute A Public Health Kev txhawj xeeb
Oct 31, 2023
COVID-19 nyob rau hauv cov chaw tiv thaiv kab mob tiv thaiv kab mob tau tshwm sim los ua teeb meem kev tswj xyuas nyuaj. Immunocompromised hosts mount cov lus teb tsis muaj zog rau SARS-CoV-2 thiab nthuav tawm qhov tshwm sim ntawm kev kis kab mob xws li kab mob hnyav mus rau tus kab mob tsis tu ncua. Lub cev tsis muaj zog txhais tau hais tias muaj cov kab mob ntau dua thiab muaj peev xwm ua rau kis kab mob. Gupta, Konnova, et al. qhia txog qhov tshwm sim ntawm cov tshuaj tiv thaiv SARS-CoV-2 variants nyob rau hauv cov neeg mob immunocompromised tom qab monoclonal antibody (mAb) kho. mAbs tsom tsuas yog ib qho kev txiav txim siab ntawm tus kab mob Spike protein, uas yog qhov tsis muaj zog ntawm cov kev kho no thaum kho tus kab mob mutagenic thiab sib txawv. Yog li ntawd, qhov tshwm sim ntawm mAb tiv thaiv tuaj yeem xav tau, tab sis nws cov ntaub ntawv tseem ceeb vim tias nws muaj kev cuam tshuam loj rau pej xeem kev noj qab haus huv, txij li cov tshuaj tiv thaiv zoo li no muaj peev xwm kis tau thiab dim kev tiv thaiv kab mob. Rau cov neeg mob immunocompromised, cov kev tshawb pom no qhia tias yuav tsum tau ua ke nrog kev kho mob nrog tshuaj tua kab mob thiab kev siv cov tshuaj tiv thaiv kab mob polyclonal xws li convalescent plasma.
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Kev kho-resistant variants
Hauv qhov teeb meem noJCI, Gupta et al. (1) qhia txog qhov tshwm sim ntawm tus kab mob SARSCoV-2 variants nthuav qhia Spike mutations nyob rau hauv cov neeg mob immunocompromised kho nrog txawv anti-Spike monoclonal antibodies (mAbs) nyob rau hauv sib txawv pandemic nthwv dej. Antibody-based antiviral therapy feem ntau ua haujlwm los ntawm neutralizing virions. Kev tiv thaiv tsis zoo tuaj yeem yog basal lossis txhim kho tom qab kho. Gupta et al. (1) qhia tias feem ntau ntawm cov kev hloov pauv no tau kho tshwj xeeb thiab tau txais kev kho mob tshwj xeeb. Cov kev tshawb pom no zoo sib xws thiab lees paub cov ntaub ntawv dhau los thiab cov ntaub ntawv me me qhia tias kev kho mAb, xws li sotrovimab (2), tuaj yeem raug xaiv rau kev kho mob-tiv thaiv cov kab mob hauv cov neeg mob uas muaj kev tiv thaiv kab mob. Txawm hais tias qhov chaw kho mob tam sim ntawd tseem ceeb ntawm qhov kev tshawb pom los ntawm Gupta li al. (1) tau raug tshem tawm los ntawm kev tshem tawm tag nrho cov tshuaj tiv thaiv Spike mAb vim qhov tshwm sim ntawm resistant Omicron sublineages, lawv cov kev paub muaj txiaj ntsig zoo rau lwm yam thiab yav tom ntej antiviral mAbs. mAb kev kho mob-kev tawm tsam xwm txheej kub ntxhov hauv cov neeg mob immunocompromised tuaj yeem xav tias yuav tau txais qhov peb paub los ntawm keeb kwm ntawm kev kho tshuaj tiv thaiv kab mob, cov txheej txheem ntawm kev ua ntawm mAbs, thiab kev hloov pauv ntawm SARS-CoV-2. Cov pov thawj tias qhov kev tawm tsam no tau tshwm sim nrog qhov tshwm sim tseem ceeb muaj kev cuam tshuam loj heev rau kev kho mob yav tom ntej thiab kev noj qab haus huv rau pej xeem cov cai hauv kev teb rau kev sib kis. Txij li thaum muaj ntau tus kab mob kis, suav nrog SARS-CoV-2, tsim ib hom kab mob sib kis hauv vivo vim yog qhov ua yuam kev ntawm tus kab mob sib kis, muaj ib txwm muaj kev txhawj xeeb tias cov kev kho mob yuav xaiv rau kev khiav tawm. Txhua mAb paub txog ib qho epitope ntawm tus kab mob ntawm qhov chaw tiv thaiv kab mob tiv thaiv kab mob, thiab cov neeg mob immunocompromised feem ntau muaj cov kab mob hauv qab ntau dua thiab ncua kev tshem tawm kab mob (raws li cov kws sau ntawv qhia txog SARSCoV-2). Xws li ib tug conundrum tsim ib tug zoo tagnrho toj roob hauv pes rau kev kho mob-emergent resistance (Daim duab 1). Nws yog ib qho yooj yim los xaiv rau cov tshuaj tiv thaiv kev khiav tawm hauv vitro los ntawm incubating tshwj xeeb mAbs nrog cov kab mob replicating, thiab cov txheej txheem no tau ua rau tus kab mob Chikungunya (3), respiratory syncytial virus (RSV) (4), thiab SARS-CoV (5. ). Kev khiav tawm txawv txav tuaj yeem tshwm sim thaum kho mAb ntawm kev sim kab mob RSV hauv paj rwb nas (6), lossis los ntawm kev tiv thaiv mAb ua ntej raug rau tib neeg (7). Li no, qhov kev tshawb pom ntawm Gupta li al. (1) tsis yog qhov xav tsis thoob, tab sis lawv tseem ceeb heev rau qhov cuam tshuam rau cov neeg mob tiv thaiv kab mob nrog COVID-19 thiab rau cov lus qhia muaj feem cuam tshuam txog kev sib kis.
cistanche cog-nce kev tiv thaiv kab mob
Kev sib tw hauv cov neeg mob immunocompromised
Raws li peb nkag mus rau xyoo plaub ntawm COVID-19 kev sib kis, cov teeb meem cuam tshuam nrog SARS-CoV-2 tus kab mob hauv cov chaw tiv thaiv kab mob tau tshwm sim raws li tej zaum qhov teeb meem kho mob hnyav tshaj plaws thiab qhov nyuaj tshaj plaws rau kev tswj hwm lub kab mob vais lav. COVID-19 nyob rau hauv cov neeg mob immunocompromised muaj peb qhov teeb meem loj: (a) cov neeg mob no tsis teb zoo rau kev txhaj tshuaj, txo cov kev xaiv los tiv thaiv tus kab mob hnyav; (b) Tus kab mob tuaj yeem ua rau mob hnyav thiab kis tau tus mob mus ntev, uas tuaj yeem cuam tshuam rau kev tsim nyog rau kev kho mob ntxiv rau cov mob hauv qab xws li mob qog noj ntshav; thiab (c) raws li qhia los ntawm Gupta li al. (1), cov neeg mob immunocompromised harbor siab dua lub hauv paus kab mob kis uas tuaj yeem pab txhawb kev tshwm sim ntawm mAb tsis kam. Qhov kev sib tw ntawm COVID-19 hauv cov neeg mob tiv thaiv kab mob ua rau cov kws kho mob muaj kev xaiv kho mob nyuaj, tshwj xeeb tshaj yog thaum kis tus kab mob mus ntxiv. Cov neeg no tuaj yeem xav tau ntau qhov kev kho mob. Tsis zoo li cov neeg mob immunocompetent uas muaj cov lus teb muaj zog thiab muaj txiaj ntsig zoo rau kev txhaj tshuaj, cov tib neeg no muaj kev tiv thaiv kab mob tsis muaj zog thiab, yog li ntawd, cov kev kho mob xws li cov tshuaj tiv thaiv kab mob me me tsis tau txais txiaj ntsig los ntawm kev tiv thaiv kab mob sib kis. Txawm li cas los xij, txhua txoj kev kho mob monotherapy, txawm tias cov no koom nrog mAbs lossis cov tshuaj tiv thaiv kab mob me me, khiav txoj kev pheej hmoo ntawm kev xaiv cov kab mob sib kis uas yuav tshem tawm lawv cov txiaj ntsig.
cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob
Nyem qhov no mus saib Cistanche Enhance Immunity khoom
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Kev tshwm sim ntawm mAb-resistant variants nyob rau hauv cov neeg mob immunocompromised kuj yog ib qho kev hem thawj rau pej xeem kev noj qab haus huv vim tias cov variants no yuav haum txaus kom xa mus rau cov neeg hauv tsev neeg (8) thiab cov neeg ua haujlwm kho mob. Xws li mAb-resistant variants kuj tseem tuaj yeem pom qhov ua rau muaj zog tiv thaiv kab mob tiv thaiv kab mob vim qhov hloov pauv loj Spike protein. Qhov tseeb, tau muaj kev txhawj xeeb tias Omicron variant tuaj yeem tshwm sim los ntawm tus kab mob mus ntev hauv tus neeg mob tiv thaiv kab mob (9).
Daim duab 1. mAb kev kho mob xaiv rau kev khiav tawm variants hauv SARS-CoV-2 kab mob. (A) SARS-CoV-2 kev kis kab mob nrog cov kab mob kis tau yooj yim (xiav squares thiab pob zeb diamond) muaj ntau qhov tshwm sim tom qab kev kho mAb, suav nrog kev tshwm sim ntawm cov kab mob tiv thaiv kab mob (txiv kab ntxwv lub voj voog). (B) Kev kis tus kab mob mAb-resistant (txiv kab ntxwv lub voj voog) tuaj yeem ua kom muaj ntau hom kab mob (txiv kab ntxwv squares thiab pob zeb diamond), yielding strains nrog lub peev xwm rau evading tshuaj tiv thaiv kab mob thiab pib kis kab mob ntxiv nyob rau hauv cov pej xeem.
Pab cov neeg mob thaum txo qis kev pheej hmoo rau pej xeem kev noj qab haus huv
Thaum lub sijhawm sau ntawv no, tag nrho cov kev kho mAb yav dhau los tau ua tsis tiav vim qhov tshwm sim ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob. Tam sim no muaj kev siv zog los tsim kho mAbs ntxiv, tab sis cov no kuj tuaj yeem ua pov thawj tsis yooj yim rau cov kev hloov tshiab tshwj tsis yog tias kev txhim kho ntawm kev tiv thaiv yog txo. Ib qho ua tau kom txo tau qhov tshwm sim uas ib qho sib txawv qhia txog kev hloov pauv uas ua kom khiav tawm ntawm mAbs yog siv mAb cocktails uas tsom tus kab mob ntawm cov epitopes sib txawv. Cov ntaub ntawv pov thawj ntawm lub hauv paus ntsiab lus rau lub tswv yim no kom txo tau qhov tshwm sim ntawm kev khiav tawm mutants tau pom nrog tus kab mob khaub thuas H5N1 hauv cov nas uas tau txais kev sib txuas ntawm mAbs (10). Txawm li cas los xij, qhov tshwm sim ntawm cov kab mob tiv thaiv kab mob los ntawm cov dej cawv uas muaj ob txoj kev kho mob twb tau tshwm sim (11-14), thiab ntau qhov sib txawv ntawm cov tshuaj tiv thaiv yuav tshwm sim thaum ib qho ntawm cov khoom xyaw cocktail tsis ua haujlwm ntawm lub hauv paus (15, 16). Tej zaum cocktails ntawm peb, raws li tsim, piv txwv li, rau Ebolavirus (17), yuav ua tau zoo dua, tab sis tus nqi tseem yog ib qho teeb meem pom tseeb.
cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob
Kev poob ntawm mAbs rau kev tiv thaiv thiab kev kho mob ntawm COVID-19 yog qhov txaus ntshai vim tias cov kev kho mob no tau txais txiaj ntsig zoo rau cov neeg mob tiv thaiv kab mob thiab lawv qhov tsis tuaj yeem ua rau cov kws kho mob muaj kev xaiv tsawg dua thaum ntsib tus kab mob SARS-CoV-2. Qhov tseeb, ntau tus neeg mob tsis txaus ntseeg muaj cov ntsiab lus tseem ceeb rau Paxlovid, thiab cov sijhawm luv luv tau tso cai rau ob qho tib si Paxlovid thiab remdesivir yuav tsis tsim nyog los tshem tawm tus kab mob. Hmoov zoo, peb muaj lwm txoj hauv kev uas tam sim no muaj nyob rau hauv daim ntawv ntawm COVID-19 convalescent plasma (CCP), uas tau pom cov txiaj ntsig kev tuag hauv cov neeg tiv thaiv kab mob hauv lub sijhawm ua ntej Omicron (18–20). Qhov tseem ceeb, CCP tau sau los ntawm cov tshuaj tiv thaiv tiv thaiv kev ua haujlwm hauv vitro tawm tsam txhua qhov tsis ntev los no Omicron sublineages (21, 22). Thiab, vim tias muaj kev kis kab mob ntau heev hauv cov neeg txhaj tshuaj tiv thaiv, xws li CCP tam sim no muaj ntau ntau. Hauv kev sib piv rau mAbs, CCP yog cov khoom lag luam polyclonal uas suav nrog cov tshuaj tiv thaiv kab mob sib txawv thiab cov txiaj ntsig ua haujlwm thiab yog li tsis tshua muaj kev xaiv rau cov tshuaj tiv thaiv kab mob sib txawv. Qhov tseeb, CCP tau siv los cawm txoj kev kho ntawm cov neeg mob immunocompromised uas tsim cov tshuaj tiv thaiv kab mob sib txawv thaum lub sij hawm kho mAb (23, 24). Ib qho kev ceeb toom tseem ceeb thaum xav txog kev kho tshuaj tiv thaiv kab mob rau COVID-19 hauv cov tib neeg uas muaj kev tiv thaiv kab mob yog tias pawg neeg mob no muaj kev sib txawv thiab peb yuav tsum muaj kev nkag siab zoo dua ntawm cov neeg mob uas yuav tau txais txiaj ntsig ntau dua (piv txwv li, seronegative). Tus kab mob COVID{14}} muaj thoob qhov txhia chaw tau pom tias cov tshuaj tiv thaiv kab mob tuaj yeem ua tau zoo thaum tseem ceeb rau peb tias cov no nyuaj dua li cov tshuaj tiv thaiv kab mob me me. Mus tom ntej, peb xav tau cov kev tshawb fawb zoo ntxiv los kawm txog kev siv cov tshuaj tiv thaiv kab mob raws li kev kho kom zoo uas peb tuaj yeem tau txais txiaj ntsig zoo rau ib tus neeg mob thaum txo qis kev pheej hmoo rau pej xeem kev noj qab haus huv rau tib neeg los ntawm qhov tshwm sim ntawm kev tiv thaiv kab mob SARSCoV-2 variants.
cistanche cov txiaj ntsig rau txiv neej-ua kom muaj zog tiv thaiv kab mob
Cov ntaub ntawv
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