Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Ntau pua xyoo ntawm kev ua pa kis thoob qhov txhia chaw Los ntawm Spanish Fu rau COVID-19 Thiab Kev cuam tshuam ntawm Nanotechnology ntawm COVID-19 Kev kuaj mob thiab kev tiv thaiv kab mob

Taw qhia

Kev kis tau sai thoob plaws qhov uas twb muaj lawm heevkis mob hnyav-Acute-Respiratory-Syndrome-2(SARS-2) lossis hu ua Coronavirus 2019 (COVID-19)kab mob, ua rau peb nco txog lwm yam kev sib kis uas tshwm simnyob rau hauv lub xyoo pua xeem (H1N1 Spanish fu) thiab txuas ntxiv musnyob rau hauv lub xyoo pua tam sim no los ntawm (SARS, MERS, thiab COVID-19) [1–3]. Tom qab ib tug series ntawm ua pa kab mob kisCov kab mob uas pib xyoo 1918-1919 los ntawm ib qho tsis paubthiab tus kab mob tuag taus hu ua H1N1 Spanish Flu thiab qee qhovCov kws tshawb fawb hu ua nws Niam ntawm Kev Sib Tw [4], vimtus kabmob kis no tau kis ntau dua li ib feem peb ntawmntiaj teb cov pej xeem thiab thov ib qho kwv yees li 50 labua neej nyob, nrog cov tsos mob tshwm sim tsis zoonyob rau hauv cov tub ntxhais hluas, yav tas los tsis muaj kab mob cov neeg laus, kev sib kistau ua qhov tseem ceeb ntawm kev tuag [5]. Hais txog qhov no,SARS-CoV-2 and 1918 influenza A/H1N1 viruses haveqee yam khoom sib xws, xws li zoo ib yamCov lej tseem ceeb tshaj tawm (R0), sib txawv ntawm 2 txog 4,thiab cov qauv zoo sib xws los ntawm cov neeg mob kis,thiab li no yuav muaj qhov sib txawv tiam neeg sib txawv. Nyob rau hauv tandem, COVID-19 tej zaum yuav muaj lub sijhawm latency zoo ib yam liuas yog mob khaub thuas [6]. Tom qab ntawd, hauv lub xyoo txhiab xyoo tam sim no,lub ntiaj teb no tau pom cov kab mob tsis tu ncua los ntawmib tsev neeg kab mob tshiab hu ua Coronaviruses (CoVs) [7]. CoVs, containing an Orthocoronavirus subfamily andTorovirinae subfamily. Te Orthocoronavirinae subTsev neeg muaj plaub hom: alpha coronavirus,beta coronavirus, gamma coronavirus thiab covdelta coronavirus [8]. Beta coronavirus genera encomkis los ntawm Severe-Acute-Respiratory-Syndrome (SARS),Middle-East-Respiratory-Syndrome (MERS), tib neegCoV-229E (HCoV-229E), HCoV-OC43, and CoronaVirus-2019 (COVID-19) [3].

Xyoo 2002, 2012, thiab 2019, lub ntiaj teb tau tawm tsam pebkab mob ua pa kab mob SARS, MERS, thiabCOVID-19, raws li. Coronaviruses tau ntim,non-segmented, positive-sense, mono-stranded RNAcov kab mob uas qhia cov yam ntxwv zoo li hauv qab negative-staining electron microscopy [9].

Cistanche Standardized Extract rau kev txhim kho lub cev tiv thaiv kab mob

Lub koom haum WHO tau tshaj tawm tias nyob rau sab qab teb Suavxeev Guangdong, lub Kaum Ib Hlis 2002, tsis muaj hloov tshiabtau txais los ntawm tsoom fwv ntawm Tuam Tshoj mus txog rau lubLub hli kawg ntawm lub Peb Hlis, muaj 792 tus neeg mob loj heev thiab 31 tus neeg tuagtau tshaj tawm. Ministry of Health ntawm Tuam Tshoj tau tshaj tawmntau dua 8,000 kis. Nws yog kwv yees tias muaj1 txhiab tus neeg mob thiab txog 774 tus neeg tuag, muabkev tuag ntawm kwv yees li 7 feem pua. Lub reservoir host ntawm lubTus kab mob no xav tias yog Asian civet miv (Pagumalarvata). Nws tau xav tias tus tswv tsev-rau-tib neeg transcov chaw tshaj tawm txoj moo zoo yuav qhib kev lag luam, ib yam li cov ntaub ntawvtam sim no COVID-19 tshwm sim. [10]. Ntiaj teb no SARSTus kab mob kis tau zoo tswj tau thaum Lub Xya Hli 2003, thiab tsis muajCov neeg mob SARS tau tshaj tawm txij li xyoo 2004. [11]. CovKev tshwm sim ntawm SARS tau ua raws li MERS ua qhov thib obtus mob coronavirus tseem ceeb tshaj plaws ua rau pej xeem thoob ntiaj tebkev noj qab haus huv xwm txheej. Thawj zaug tshwm sim hauv Saudi Arabia (KSA)xyoo 2012 thaum tus neeg mob hnub nyoog 60 xyoo muaj mob ntsws loj heev[10]. Ib qho kev sib kis ntawm tus kab mob tsuas yog tshwm sim hauv2014, nrog rau tag nrho cov ntaub ntawv txheeb xyuas ntawm 662 thiab ib rooj plaubKev tuag index ntawm 32.97 feem pua. Los ntawm 2014 txog 2016, 1364 tus neeg mobtau pom hauv KSA [10]. Zuag qhia tag nrho, 27 lub teb chaws muajtau cuam tshuam los ntawm MERS thaum muaj kev sib kis, hauv Asia,Teb chaws Europe, Middle East, thiab North America. [12]. Covcov ntaub ntawv txheeb xyuas dhau ntawm Middle East, suav nrogKaus Lim Qab Teb (SK) kis mob uas 186 tus neeg muajtau pom tias muaj tus kabmob kis los ntawm kev kis tus kabmob supering, tau koom nrog cov neeg tau txais kev hloov pauv uas twb muaj lawmtau kis nyob rau hauv Middle East. Txij li thaum 2012, tag nrho ntawm2494 qhov kuaj pom tseeb ntawm MERS tau tshaj tawm,nrog 858 tus neeg tuag uas muaj feem cuam tshuam (tus neeg mob tuag taus ntawm 34.4 feem pua)[10].

Hais txog COVID-19, WHO tau tsa qhov kev pheej hmootheem ntawm tus kab mob CoV mus rau "siab heev" rau 28 Lub Ob Hlis 2020.Thaum Lub Peb Hlis 11, raws li COVID-19 tshwm sim sab nraum Tuam Tshojnce los ntawm ib qho ntawm 13 thiab tus lej ntawm tus kabmoblub teb chaws tau nce peb npaug rau ntau dua 118, 000 sau npemob hauv 114 lub teb chaws sib txawv, nrog ntau dua4,000 cov neeg tuag, WHO tshaj tawm COVID-19 thoob ntiaj tebkev kis kab mob mus thoob. Tsoom fwv thoob ntiaj teb ua haujlwmmuab cov kev tawm tsam hauv qhov chaw los tuav lub peev xwmdeleterious teebmeem. Cov koom haum noj qab haus huv tab tom koom teskev khiav ntawm cov ntaub ntawv thiab muab cov lus qhia kom zoo tshaj plawstxo qhov cuam tshuam ntawm kev hem thawj kis thoob qhov txhia chaw. Lub caij no,cov kws tshawb fawb los ntawm thoob plaws lub ntiaj teb tab tom ua haujlwm hnyavthiab cov ntaub ntawv ntawm kev sib kis mechanisms,kev soj ntsuam spectrum ntawm kev kuaj mob tshiab ntawm tus kab mob, kev tiv thaiv, thiab kev kho mob yog tsimceev ceev. Ntau yam tsis paub txog tus kab mob-tus tswv tsevdynamic thiab kev nce qib ntawm kev sib kis tseem nyob,nrog rau lub sijhawm ntawm nws lub ncov [13].

Nanomaterials (NMs) muaj cov yam ntxwv tshwj xeeb uas yogtshwj xeeb, uas characterize lawv raws li zoo heev cov ntaub ntawvtuaj yeem siv rau hauv cov khoom siv spectrum, sensors, thiab cov txheej txheemsiv hauv kev tshawb nrhiav tus kab mob, kev kho mob, thiab tus kab mobtshem tawm ntawm ib puag ncig [14]. Ib feem tseem ceeb ntawmCov ntawv thov ntawm NMs yog los twv thiab kho cov kab mob hauvkev kho mob thiab ib puag ncig. Hauv kev tshuaj xyuas no, peb yognthuav qhia luv luv txog qee qhov kev siv no.

Keeb kwm ntawm kis kab mob ua pa kab mob viral

Avian influenza yog qhov txawv ntawm nws lub peev xwmkis kab mob ntau yam tsiaj, nrog rau homxws li puav, noog, thiab tsiaj txhu. Txawm tias muaj kev vam meejKev sib kis sib kis tsis tshua muaj, nws ua lub luag haujlwm tseem ceebnyob rau hauv tiam tshiab vectors ntawm kev sib kis [14]. Hauvkev sib kis ntawm 1918-1919, Lub Peb Hlis 1918 yog qhov pibntawm lub caij nplooj ntoos hlav nthwv dej. Nws kis thoob plaws Tebchaws Europe, Asmeskas, thiabAsia dhau rau lub hlis tom ntej. Txawm tias theem ntawm tus kab mobtau siab, cov neeg tuag feem ntau tsis yogsiab dua li niaj zaus. Ib tug thib ob los yog lub caij nplooj zeeg nthwv dejkis thoob ntiaj teb txij lub Cuaj Hli mus txog Kaum Ib HlisXyoo 1918 thiab tuag taus heev. Hauv ntau lub tebchaws, ib nthwv dej thib pebtshwm sim thaum ntxov 1919. Cov neeg soj ntsuam tam sim no xauslos ntawm kev kho mob zoo sib xws uas lawv tau pomtib yam kab mob sib kis hauv cov nthwv dej txuas ntxiv [4]. TeCov ntaub ntawv me me ntawm cov kab mob sib kis hauv tag nrho peb lub nthwv dej tau raugTus kab mob khaub thuas pom nyob rau xyoo 1889 muaj thoob qhov txhia chaw thiabavian fu kab mob sib kis thiab xyoo dhau los inter-pandemic. Hauvsaib ntawm qhov no, txawm tias qhov nrawm nrawm los ntawm kev tsis ua rawscated influenza infection to fatal pneumonia, yam ntxwvntawm lub caij nplooj zeeg thiab lub caij ntuj no nthwv dej ntawm 1918-1919, yogpom nyob rau hauv ob peb qhov mob hnyav nyob rau hauv lub caij nplooj ntoos hlav nthwv dej [4, 15].

Up to 2003, only 2 CoVs, Human CoV 229E (HCoV-229E) and HCoV-OC43 has been know to lead totib neeg kab mob [16]. Nws tshwm sim raws li cov tsos mob me xws liraws li ib tug mob khaub thuas nyob rau hauv cov neeg laus thiab mob hnyav dua nyob rau hauvcov menyuam mos, cov laus, thiab cov neeg tiv thaiv kab mob. HauvKaum Ib Hlis 2002, ntau qhov tshwj xeeb ntawm "atypicalmob ntsws o" ntawm unexplained yog vim li cas tau tshaj tawm nyob rau hauvnroog Foshan, Guangdong Province, Suav teb, qhov twgntau tus neeg ua haujlwm noj qab haus huv tau kis kab mob [17]. Tsi yogtau qhia rau Hong Kong thaum Lub Ob Hlis 21, 2003 los ntawm tus kws kho mobuas tau cuam tshuam nrog cov xwm txheej zoo sib xws ntawm SARS hauv Suavthaj av loj, uas ua rau muaj kev mob ntsws loj heevhauv Hong Kong thiab sau npe los ntawm WHO tias "mob hnyavacute respiratory syndrome" rau lub Peb Hlis 15, 2003 [18, 19]. Lub hli dhau mus, thiab ntau qhov xwm txheej ntawm SARS muajtau txheeb xyuas ua ntej SARS-CoV raug txheeb xyuas. Ib tug tshiabb-CoV (SARS-CoV) of lineage B is confirmed as theua rau muaj tus mob SARS mob ntsws rau 22 Lub Peb Hlis 2003.Tus kab mob SARS-CoV tau kis mus rau 29 lub tebchawsthiab cheeb tsam. Nws tau pom tseeb tias lub ntiaj teb kev noj qab haus huv, Medical, thiab scientific kev loj hlob zej zog tsis tautxaus npaj rau qhov tshwm sim ntawm SARS. [18]. Tib neeg-rau-tib neeg txoj kev sib kis tau tshwm simHauv Canada, Toronto, Suav Taipei, Hong Kong, Suav,Vietnam Singapore, thiab Hanoi. Tau muaj tus kab mob SARSkeeb kwm luv luv thiab WHO tshaj tawm txoj kev windingpoob ntawm tus kab mob SARS thaum Lub Xya Hli 2003 [18].

Kaum xyoo tom qab kos npe kawg ntawm SARS-CoV, thaum Lub Rau Hli2012, ib tug txiv neej tuag hauv KSA ntawm mob ntsws loj thiab raumqaug zog [20]. Tus mob coronavirus tshiab,Middle-East-Respiratory-Syndrome-Coronavirus(MERS-CoV), has been identified from his sputum [21]. Ib pawg neeg mob ua pa hnyav tau tshwm simLub Plaub Hlis 2012 hauv Jordan hauv tsev kho mob thiab tau kuaj pomnyob rau hauv retrospect li MERS12 thiab ib pawg ntawm peb MERS-infectedCov neeg mob hauv tebchaws Askiv tau kuaj pom thaum lub Cuaj Hli2012 MERS-CoV tau nce mus ntxiv thiab nthuav tawm sab nraudlub "Arabic ceg av qab teb". Raws li qhov tshwm sim ntawm kev mus los ntawmcov neeg kis kab mob; feem ntau cov tshiab transCov kab mob MERS tau ua rau raug mob hauv tsev kho mobkis tau tus mob [22]. Thaum lub Tsib Hlis 2015, MERS tau tshwm sim hauvSK tau tshwm sim los ntawm ib tus neeg rov qab los ntawm Nruab NrabSab hnub tuaj thiab cuam tshuam kaum rau lub tsev kho mob thiab 186 tus neeg mob. Raws li 26Lub Plaub Hlis 2016, 1,728 tus neeg mob MERS tau lees paub, ntawmuas 624 tus neeg tuag hauv 27 lub tebchaws sib txawv [22]. 

Ib pawg neeg mob ntsws uas muaj feem cuam tshuam nrog ib qho kev tshawb pom tsis ntev los no- tus mob coronavirus tau tshwm sim hauv Wuhan, Tuam Tshoj, hauvLub Kaum Ob Hlis 2019. Lub Ib Hlis 12, 2020, Ntiaj Teb Kev Noj Qab Haus HuvLub koom haum (WHO) tau xaiv tus kabmob coronavirus no ua tus tshiab 2019coronavirus (2019-nCoV) (WHO). InternaPawg Neeg Saib Kev Kawm tau npaj lub npe tshiab uas tau txheeb xyuascoronavirus as SARS-CoV-2, ob leeg tau tshaj tawm rau 11 Lub Ob HlisLub Rau Hli 2020. Cov kws tshawb fawb Suav tau cais tawm SARS saiCoV-2 from a patient on 7 January 2020. Tey came outto genome sequencing of the SARS-CoV-2. Raws li 1 Lub Xya Hli2021, 91,833 tus neeg mob ntawm COVID-19 tau lees paub hauvSuav teb loj suav nrog 4636 tus neeg tuag. Kev tsim tawm yooj yimnumber "R0" of SARS-CoV-2 is assessedlos ntawm kev tshawb fawb kom nyob ib puag ncig 2.2 lossis ntau dua (ntau 1.4–6.5), thiabtsev neeg pneumonia tshwm sim pab pawg ntxiv rau cov pov thawj ntawmkev kis tus kab mob COVID-19 tsis tu ncua los ntawm tib neeg mus rau tib neegkis tau tus mob (Fig.1) [23]. Raws li lub WHO (https://covid19.who.int/); thoob ntiaj teb, txij li 8:36 teev tsaus ntuj CEST, 14 Plaub Hlis 2022, muajtau 500,186,525 tus neeg mob uas tau lees paub los ntawm COVID-19, suav nrog6,190,349 tus neeg tuag, tshaj tawm rau WHO. Raws li lub Plaub Hlis 182022, muaj tag nrho ntawm 11,307,908,653 koob tshuaj tiv thaivtswj hwm.

Reservoir thiab hom kev sib kis

Cov kab mob khaub thuas nyob rau hauv ntau hom yog paub tias loshauv hav zoov. (Fig.2) [24]. Hos tib neeg- npuakis tau tus mob subtypes twb tau qhia thiabsubstantiated, direct kis ntawm noog thiabtib neeg tsis tshua muaj tshwm sim (xws li H9N2thiab H5N1 subtypes) tab sis muaj qee qhov tshwm simcov neeg tuag. [25].

Lub reservoir ntawm tsev neeg coronaviridae uasmuaj cov kab mob beta-coronavirus suav nrog peb tus kab mob pandemics tsis ntev los no (SARS, MERS, COVID-19). Bats yog ib tug lojnatural reservoir wide range of CoVs, including SARS-CoV-likeand MERS-CoV-like viruses (Fig.2). Ua rawstus kab mob genomic sequence, COVID-19 tau kawm,the genome for Bat CoV RaTG13 showed 96.2 percentzuag qhia tag nrho tus kheej ntawm genome series, qhia txog CoVbat Txawm tib neeg SARS-CoV-2 tej zaum yuav muaj tib tus niam txivhnub nyoog. Hauv qhov sib piv, cov puav tsis tuaj yeem siv tau rau kev yuav khoom hauv qhov nokev lag luam seafood. Los ntawm txoj kev, lub synchronizationntawm cov protein ib ntus thiab kev tshawb fawb ntxiv phylogeneticqhia pom zoo li residue receiver tau pom nyob rau hauv ob pebhom, uas muaj ntau possibilities rau alternatenruab nrab hosts; Rau pib, tortoises, pangolin, thiabkhoom noj txom ncauj [23].

Tag nrho cov kab mob kis tau tus kab mob ua pa yog zoonotic huab cuaCov kab mob RNA uas tsis tshua kis tau ntawm nruab nrabhaiv neeg cov ntaub ntawv tab sis tuaj yeem hloov mus ua tib neegkis tau tus mob zoo dua. Nquag thiab pom zootransmission routes droppings (>5mm txoj kab uas hla, yaKev sib kis'<1  m) make contact with the nose with Cov kab mob uas siv tau, qhov ncauj, qhov muag, lossis txoj hlab pa sab saud thiab 'airbornekis tau tus mob 'qhov twg cov tee dej (5 hli txoj kab uas hla) yogkernels [27]. 2002 thiab 2003 yog piv txwv ntawm H1N1Tus kab mob khaub thuas kis thoob qhov txhia chaw hauv SARS thiab 2009.

Te ua haujlwm ntawm 'kev sib txuas lus ncaj qha ntawm kov' (tsis muajqhov ua tau ntawm qhov chaw qias neeg) thiab 'indirectkov propagation' (nrog rau qhov chaw muaj kab mob) ntawm covkev faib tawm ntawm cov kab mob kis thoob qhov txhia chaw muajtau teeb meem. Txawm li cas los xij, ntau yam ntawv ceeb toom thiabkev tshawb nrhiav tau qhia tias kev sib txuas lus ncaj qhakis tau tus mob ntau. Koj kis tau tus mob rauLwm yam kab mob ua pa, nrog rau mob khaub thuas, nyob rau hauv qee yamtej yam kev mob [26].

Replication of SARS-CoV-2 virus

Tus kab mob khaub thuas replication tshwm sim ntawm qib cellularfeem ntau nyob rau hauv lub epithelial hlwb ntawm txoj hnyuv nyob rau hauvnoog thiab nyob rau hauv lub epithelial hlwb ntawm txoj hlab ntsws nyob rau hauvtib neeg thiab lwm yam tsiaj txhu [27]. Hauv tib neeg, ribonucleoproteins(vRNPs) tom qab kis mus rau hauvlub nucleus ntawm cov kab mob uas muaj kab mob, uas kis tau tus kab mob RNA transcriptsthiab replicates los ntawm kev ua haujlwm enzymatic ntawmcov kab mob polymerase complex txuas rau vRNPs [28]. Tereplication ntawm tus kab mob RNA tshwm sim ntawm qhov zoo intermedianoj, lub complementary ribonucleoprotein complex [29]. Kev hloov pauv ntawm tus kab mob-RNA ua rau muaj txiaj ntsig zoomRNA uas yog cap-txuas thiab polyadenylated thiab tom qab ntawdxa mus rau cytoplasm kom muab txhais ua cov kab mob kis kab mob. [30]. Cov kab mob tshiab tau tsim cov polymerases (PA,PB1, thiab PB2) thiab cov kab mob NP raug xa mus rau hauv lub nucleuskom nce tus nqi ntawm viral-RNA synthesis, thaum tus kab mobmembrane proteins HA, NA, thiab M2 yog thauj thiabmuab tso rau hauv plasma membrane [31].

MERS-CoV and SARS-CoV have a specific codingmechanism nyob rau hauv uas hais txog ob feem peb ntawm "viralRNA" tau muab txhais ua ob yam loj heev polyproteins, thaumtus kab mob genome tseem tshuav yog transcribed nyob rau hauv ib qho zesseries ntawm subgenomic mRNAs [22]. Hauv ob qho tib si pp1a thiabpp1ab, polyproteins encode kaum rau cov proteins uas tsis yog qauv. (nsp1–nsp16) uas coj cov kab mob rov ua duaTransscriptase complex [32]. Cov polyproteins yog cleavedlos ntawm papain-zoo li protease (PLpro; sib xws rau nsp3)ob proteases, thiab Te protease, 3C-zoo li protease(3CLpro; sib xws rau nsp5). nsps rov npaj membranes muab tau los ntawm ntxhib endoplasmic reticulum(RER) mus rau hauv ob-membrane vesicles, nyob rau hauv uas lubtus kab mob transcription thiab replication tshwm sim. Koj exoribonuclease (ExoN) kev ua haujlwm ntawm nsp14 yog qhov tshwj xeebntawm tus mob coronaviruses, uas muab kev khomuaj peev xwm tsim nyog los txhawb nqa lub RNA genome lojtsis accumulating teeb meem mutations. MERS-CoVand SARS-CoV transcribe 9 and 12 subgenomic RNAsraws. Tese encode plaub yam qauv proteins,uas yog cov protein ntau (S), hnab ntawv (E), nucleocapsid(N), daim nyias nyias (M), thiab ntau yam khoom siv proteins uastsis txhob koom nrog hauv viral replication tab sis cuam tshuam nrogtus tswv tsev lub cev tiv thaiv kab mob los yog nws txoj haujlwm yogtsis paub los yog to taub yuam kev.

Lub hnab ntawv "E" spike glycoprotein "S" clings rau nws cellularreceptor, angiotensin-hloov enzyme 2 (ACE2)for SARS-CoV and dipeptidyl peptidase 4 (DPP4) forMERS-CoV. Cov "viral RNA genome" raug xa mus rau hauvLub cytoplasm tom qab membrane fusion, emissions mus rau lubtus tswv tsev cell membrane los yog mus rau endosome membrane.Te RNA yog unwrapped kom tso cai txhais ntawm obpolyproteins, transcription ntawm subgenomic RNAs, thiabreplication ntawm tus kab mob genome. Te resulting hnab ntawvglycoproteins tau nkag mus rau hauv RER lossis Golgi daim nyias nyias; genomic RNA thiab nucleocapsid proteins tuajua ke los tsim cov nucleocapsids. Virus particle budhauv ER-Golgi intermediate compartment (ERGIC). CovCov kab mob uas muaj kab mob ces fuse nrog cov plasma membranekom xa tus kab mob [22]. 

Hais txog COVID-19 (Fig.3), genomic RNA yog sivraws li scaffolding ncaj qha txhais polyprotein 1a/1ab(pp1a/pp1ab), uas encodes non-structural proteins(nsps) los ua qhov replication-transcription complex(RTC) nyob rau hauv ob-membrane vesicles (DMV). Thaum kawg,ib pawg nested ntawm subgenomic RNAs (sgRNAs) yog synthesizedlos ntawm RTC nyob rau hauv ib tug discontinuous hom ntawm transcription. Cov tub txib subgenomic RNAs (sgRNAs)muaj common 5′-cov thawj coj thiab 3′-terminal sequences. thiabTom qab tau txais thiab Transcription terminationntawm tus thawj coj RNA tshwm sim ntawm kev tswj hwm kev hloov pauvCov kab ke nyob nruab nrab ntawm cov ntawv nyeem qhib (ORFs).Cov minus-stranded gRNAs ua raws li tus qauv rau subgenomicmRNA ntau lawm.

Ib yam CoV genome thiab subgenomes suav nrog ntawmyam tsawg kawg yog rau ORFs. Thawj "ORFs (ORF1a/b), uassuav txog li ob feem peb ntawm tag nrho cov genome ntev,code rau 16 naps (nsp1-16), nrog rau kev zam ntawm Gammacorona virus, uas tsis muaj nsp1. Muaj ib−1 framhloov ntawm ORF1a thiab ORF1b, uas ua rau kev tsim khoomntawm ob polypeptides: pp1a thiab pp1ab. Tes polypeptides raug kho rau hauv 16 naps los ntawm tus kab mob-encodedchymotrypsin-zoo li protease (3CLpro) los yog master protease(Mpro) thiab ib lossis ob lub papain zoo li proteases. Lwm yamORFs ntawm ib feem peb ntawm genome nyob ze ntawm 3′- lus encodeyam tsawg kawg yog plaub lub qauv loj "cov proteins: (S), (M), (E), thiab(N) [33]. Ntau yam CoVs encode tshwj xeeb cov qauv thiabNtxiv cov protein, xws li HE protein, 3a / b protein,thiab 4a / b protein, ntxiv rau plaub qhov yooj yim nostructural proteins. CoV sgRNAs yog siv los txhais tag nrhostructural thiab accessory proteins [34].

Viral adaptation xav tau rau tus tswv hloovthiab determinants ntawm pathogenicity

Influenza A tus kab mob yuav tig tau tus tswv thiab tsim ib qho kev tsim tshiabcaj ces [35]. Tus kab mob no, hu ua zoonoticmuaj lub sijhawm los hloov tus kabmob mus rau tus tswv tsev tom ntej, thiabqhov tshwm sim muaj thoob qhov txhia chaw. Thaum tus kab mob khaub thuas A nkag muslub cev, grippe HA (hemagglutinin) moleculetxais sialic acid (N-acetylneuraminic) nyob ib ncig ntawm sab saum tojntawm lub host cell [36]. HA yog ib hom transmembrane glycoprotein ua homotrimer qhia rau daim ntawv kab mob.Txhua monomer yog tsim los ntawm ob subunits, HA2 thiabHA 1. Hauv thaj av endosome qis pH, cleaved HA nrog afusogenic HA2 stalk domain fusion mediates endosomaldaim nyias nyias nrog cov kab mob viral, uas ua rauTus kab mob nkag mus rau lub zog ribonucleoprotein (vRNP) rau hauv lub cell[37]. 

Lub "vRNP complex muaj 8 ib leeg-stranded,negative-sense nucleoprotein (NP) vRNA, thiab RNAs rauInfluenza-A Polymerase" (PA, PB1, thiab PB2 compound)[28]. Nrog kev sib xyaw ua ke tom qab, vRNP complex tuaj yeemraug tso tawm hauv lub cell cytoplasm, tom qab uas nws nkag muslub nucleus los ntawm kev xa khoom tiav [37]. Te nucleusyog qhov chaw RNA synthesis ntawm tag nrho cov kab mob khaub thuas sivqhov chaw. Pib txheej txheem transcription; RNA polymerasetus kab mob khi rau qhov khaws cia thiab yuav luag ua tiav13 ntawm qhov kawg ntawm 5' nuclear fais fab thiab 12 kawg ntawmLub 3' nucleotide" yim ntu. Txawm li cas los xij, cov polymeraseTus kab mob khaub thuas tsis muaj kev ua haujlwm capping. Nwssummarizes RNAs siv 5 'host cap pre-mRNAs viral massager Ib qho tshwj xeeb "cap snatching" mechanism kev sib khoPB1 thiab PB2 muab tau los ntawm cellular transcriptions protein[28]. Nonstructural NS1 protein cuam tshuam rau tus kab mob morphogenesis tom qab nyob rau hauv viral replication voj voog hais. Txawm li cas los xij,lawv tsis yog cov kab mob sib kis [38].

Receptor identification sawv cev rau theem pib ntawmkab mob kis kab mob ntawm cov kab mob hauv tsev thiab yog ib qho tseem ceeb tshaj plawscov xwm txheej hauv kev kis kab mob thiab pathogenesis [39]. Txawm hais tias muaj ntau tus tswv tsev- thiab tus kab mob cuam tshuam txog tuaj yeem ua taukuj cuam tshuam qhov ua tau zoo ntawm kev kis kab mob thiab rov ua dua tshiabntawm tus kab mob nyob rau hauv ib lub tswv yim tshwj xeeb, cov yam ntxwv no nkaus xwbtuaj rau hauv kev ua si thaum tus kab mob txuas mus rau lub cell membranetus txais [40]. Coronaviruses (CoVs) have anenveloped, ib leeg-stranded-RNA genome uas encodesplaub daim nyias nyias proteins, uas yog spike, membrane,hnab ntawv, thiab nucleocapsid proteins raws li qhia hauv daim duab.3 [2, 41]. S proteins yog ib qho tseem ceeb rau kev kis kab mobkab mob pathogenicity [42]. On the SARS-CoV envelope "E", ib tug trimeric S mediates tus nkag mus ntawm lubtus kab mob mus rau hauv lub host cell. Nws thawj txuas mus rau nws tus tswv tsev txais,angiotensin 2 converting enzyme (ACE2), thiabfuses tus tswv tsev thiab tus kab mob membranes tom qab [43]. Ib qho muab receptor-binding-domain (RBD) ntawm "S"SARS-CoV yog txaus los khi nrog highaffinity rauACE2 [44]. Ib qho tseem ceeb ntawm cov kab mob pathogenesisSARS-CoV and cross-species infectionstxheeb xyuas raws li RBD / ACE2 binding affinity [45]. Covkev sim cross-reactivity ntawm anti-SARS-CoV antibodiesnrog 2019-nCoV spike proteins, uas tej zaum yuav muajqhov tseem ceeb rau kev tsim khoom saintawm cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv tiv thaiv 2019-nCoV,yog li ntawd urgently xav tau [46].

Virulence yam ntawm tus kab mob kis thoob qhov txhia chaw

Virulence factor yog suav tias yog ib qho tseem ceeb ntawm cov khoomuas plays lub luag haujlwm tseem ceeb hauv kev hloov kho tus kab mob mus rau hauvhost cell [47]. Hais txog kab mob khaub thuas, Haemagglutinin(HA) yog ib feem ntawm qhov chaw glycoproteinkab mob vais lav. nrog ob lub luag haujlwm tseem ceeb hauv lub sijhawm ntxov tshaj plaws ntawmTus kab mob replication: membrane fusion thiab receptor txuas[48]. HAs ntawm tus kab mob khaub thuas Avian siab kab mob tau teeb tsatseem ceeb pab rau virulence. Lawv feem ntau muajib theem zuj zus (piv txwv li ib ntu ntawm cov amino acids yooj yimnyob rau ntawm qhov chaw cleavage uas yuav pab kom muaj ntau ntawm pathogenicity). [49]. Cov qauv no, txawm tias nws tsis xav txognyob rau hauv HA ib ntus ntawm 1918. Txawm li cas los xij, nws tau uaqhia tau hais tias tus kab mob rov hais dua nrog keeb kwm caj ces1918 HA rov ua dua ntawm qhov kev nce qib siab hauvmob ntsws, thiab nrog rau lub ntsws loj ntawm lub ntsws los ntawm neutrophilsthiab alveoli macrophages ua rau mob ntsws loj heev. Tus kab mob 1918 tiag tiag nrog kev mob hnyav thiabKev tuag tom qab pom cov txiaj ntsig zoo sib xws. Cov txiaj ntsig noqhia txog lub luag haujlwm tseem ceeb hauv tus kabmob ntawm tus kabmob 1918rau HA gene [50]. Qhov chaw muaj kab mob siab (s) ntawm HAtseem tsis tau pom dua. Lwm qhov tseem ceeb hauv nruab nrabxyoo 1918 kev tshwm sim yog virulence. Ib tug txawv txawv yam ntxwvntawm kev sib kis ntawm xyoo 1918 yog ntau tus neeg muajdhau los ntawm kab mob ntsws ntsws; kab mob khaub thuas kab mob hauv lubpulmonary system ntawm cov neeg mob feem ntau replicateua tsis zoo thiab feem ntau ua rau muaj kev phom sij rau lub neej [51]. Nyob rau hauv lub pulmonary system ntawm cov kab mob filamentsthiab tsis yog tib neeg primates, peb sau ib qho effectivereplication ntawm tus kab mob 1918, uas ua rau kis tus kab mobmob ntsws o.

Hauv kev sib piv, lub ntsws ntawm cov tsiaj muaj mob tsis taumuaj tus kab mob H1N1 tib neeg tam sim no, txawm tias nwsreproduced nyob rau hauv qhov ntswg kab noj hniav. Yog li ntawd, peb xaus lustias tus kab mob 1918 lub peev xwm nthuav dav hauv lub ntsws yogmuaj feem xyuam rau nws siab tib neeg virulence [51]. Nws kuj tau sau tseghais tias cov kab mob titers siab yog nyob ntawm NP noob thiabpolymerase nyob rau hauv lub ntsws ntawm tus kab mob ferrets nyob rau hauv 1918 [52]. Polymerase noob kuj tseem ceeb hauv cov kab mobthiab kis tau tus nas hauv ferrets [53]. Cov noCov txiaj ntsig tau cuam tshuam nrog tus kab mob RNA polymerase complex hauvkev ua tiav ntawm kev kis tus kab mob mus rau qhov ua pa qistract thiab qhia tias, ua ke nrog ib qho tshwj xeebHA, tej zaum nws yuav txaus los ua rau mob ntsws tuagThaum muaj kev sib kis ntawm 1918-1919 [54]. Pathogenicitykuj tuaj yeem cuam tshuam nrog lwm yam kab mob xws li covrooj plaub ntawm kev sib kis NA, NS1, PB1-F2, thiab lwm yam hauv xyoo 1918.Pro-apoptotic viral protein PB1-F2 tsuas yog xav tauhloov nyob rau hauv ib qho amino acid ntawm 66th txoj hauj lwm los txhim khotus kab mob virulence ntawm 1918 [51]. Xyoo 1918 PB1-F2Kev nthuav qhia txhawb nqa pulmonary pathology hauv thawjkab mob kis kab mob thiab kis kab mob thib ob [51].

Kev hwm beta coronaviruses (SARS, MERS, thiabCOVID-19), lawv muaj E protein ntauactive motifs ntawm 76 thiab 109 CoV-dependent aminoacids muab nws txwv loj [55]. Kev hloov kho lossis kev tawm tsamntawm E protein nyob rau hauv sib txawv CoVs ua rau cov kab mobnrog sib txawv phenotypes thiab txawv txawv interrelationshipsnruab nrab ntawm tus kab mob thiab tus tswv tsev nrog rau kev ntxhov siab inductionthiab cov tshuaj tiv thaiv protein los yog kev hloov hauv cov concentrations nrogcellular ion vim E protein ion channel kev ua [55, 56]. Tag nrho cov kev coj ua no muaj qhov cuam tshuam tseem ceeb rau covpathogenesis of CoV. Tsis tas li ntawd, hauv COVID-19 "S" yoglub ntsiab txhais ntawm cell tropism thiab yog li ntawd interspecies kis ntawm CoVs, vim nws khi tus kab mob mus rau lub cellularreceptor thiab ces catalyzes membrane fusion nkagntawm tus kab mob vais lav [57]. Electron-microscopy 3D qauvntawm 2019-nCoV viral S qhia nws qhov zoo sib xws nrog covS of the other COV [57]. Cov yam ntxwv ntxiv ntawmLwm yam CoVs tuaj yeem raug txiav tawm. Viral S yog transmembranehom I transmembrane protein nrog lub n-terminalcleavable teeb liab peptide, loj thiab siab n-glycosylatede, ib tug transmembrane, thiab cytoplasmic tail embedded nyob rau hauvib qho S-collated residue pawg [57]. Lub ectodomain muajtau muab faib ua qhov sib txawv heev S1 sau ntawmlub genera thiab S2 domain uas yog kev txuag ntau dua thiabcatalyzes membrane fusion. Tus neeg txais kev khi lus operation ua rau pathogenicity [58].

Cov tsos mob thiab kev kho mob tshwm sim

Tus kab mob khaub thuas H1N1 kis thoob plaws xyoo 1918-1919 witness variations nyob rau hauv cov tsos mob thiab cov tsos mob raws li ntauyam xws li qhov mob hnyav, tus neeg lub hnub nyoog,thiab lub caij [59]. Qhov mob me me, tsis meej pem raws li tau hais tsegnyob rau hauv lub caij nplooj ntoos hlav herald nthwv dej muaj cov tsos mob ntawm tusua pa sab sauv, xws li mob caj pas, nasopharyngitis, thiab hnoos, nrog rau cov kev tshwm sim ntawm lub cevkub taub hau, myalgia, thiab prostration (Fig.4) [60]. Epistaxistau ua nyob rau hauv ob qho tib si mob me thiab mob hnyav [61]. Koj tus kws kho mob qhia txog tsob ntoo txhiab tus neeg mob ntawm CampFremont tau sau tseg tias epistaxis yog ib tus yam ntxwvntawm tag nrho cov kab mob sib kis [60]. Qhov no tau txiav txim siabtus yam ntxwv ntawm tus kab mob raws li ntshav ib txwm nchuavlos ntawm qhov ntswg thiab qhov ncauj ntawm tus neeg mob. Lub sijhawmntawm qhov mob nruab nrab feem ntau txwv rau 72 teev. Feem ntau, hnoos tsis ua haujlwm. Ua npaws ntau heevmus txog 104 degree F. Qee lub sij hawm tam sim ntawd thiab heev prostration[62]. Ib tug txhais ntawm tus neeg mob li "ceev los yog yuav luagunexpectedly seized nrog kev nkag siab ntawm prostration uas yogtsis muaj peev xwm ua txhua yam nws ua tau. MuajQhov tseem ceeb ua pa nyuaj rau cov neeg mob uas muaj mob hnyav [62]. Lawv cov tsos mob muaj xws li khaus heevcyanosis, kev tshaib kev nqhis hauv huab cua, txo kev paub, thiab nthuav davbubbling rales ntawm kev mob ntsws edema heev(Fig.4). Te cyanosis ntawm heliotropic cyanosis pom nyob rau hauvQee cov neeg mob ua ntej tuag tom qab heliotrope fover'ssib sib zog nqus xiav los yog ntshav liab. Cov kws kho mob kuj frst nco ntsoov tiasdaim di ncauj thiab pob ntseg yog xim xiav ua ntej tsom rautus so ntawm lub ntsej muag [31]. Nyob rau hauv tsab ntawv mus rau ib tug npoj yaig tus kws kho mob, ib txhia piav cov xim li purplish-dub thiab ib tugTus kws kho mob Scottish uas ua haujlwm hauv camp Deven tau sau tseg tias"cov txiv neej xim rau dawb tsis yooj yim rau kev paub qhov txawv." Hauvcov xim txawv txav, tus kws kho mob txiav txim siab tias cyanosisyog vim muaj exudations nyob rau hauv lub alveoli tiv thaivtsim nyog oxygenation thaum rov spectrographic tswjntawm tus neeg mob cov ntshav tsis pom [60]. Ob tug kws kho mob hlwbtej yam kev mob ntsig txog, rau mob ua pa nyuaj.Rapid Mortality Syndrome (ARDS), thiab cov neeg mob tuag tausKev txheeb xyuas ntawm bronchopneumonia. Cov kab mob thib obTus kab mob ua rau bronchopneumonia ua raufeem ntau tuag nrog mob ntsws, tshwj tsis yog cov neeg raug tuaXyoo 1918 tom qab kis tus kab mob H1N1 [60]. Initial leukoPenia tau ua raws li bronchopneumonia leukocytosis [63]. Brundage thiab Shanks [64], kaw qhov nruab nrablub sij hawm ntawm 7-10 hmo los ntawm qhov pib muaj mob thiab ob peb deaths>15 hnub tom qab qhov pib, ua ke nrogSecondary bacterial pneumonia, rau feem ntau cuam tshuampej xeem.

Nyob rau hauv cov ntaub ntawv ntawm SARS, kub taub hau, chills, rigors, myalgia, qhuavco toxins, dyspnea, malaise, thiab mob taub hau yog qhov txawvCov yam ntxwv kho mob ntawm SRAS [65]. Nrov duamuaj mob caj pas, raws plab, rhinorrhea, xeev siab, ntuav,thiab o [65]. Hauv 40-70 feem pua ​​​​ntawm cov neeg mob SARS, dejmob raws plab. Nws zoo li tshwm sim li 7 hnubtom qab qhov pib ntawm tus kab mob [18]. Ob tug neeg mob ua rawscated nrog epileptic xwm txheej tau kuaj pom hauv cov ntshav thiabcerebrospinal kua. Cov neeg laus SARS-CoV-infected cov neeg mobtuaj yeem txhim kho qhov qab los noj mov, txo qis hauv kev noj qab haus huv tag nrho, poob pob txha, thiab tsis paub tseeb, tab sis tej zaum yuav ua tsis tautxhawm rau nce febrile cov lus teb rau qee cov neeg laus [66]. Hauv kev sib piv, tus kab mob SARS-CoV feem ntau yog me meHauv cov menyuam yaus hnub nyoog qis dua 12 xyoos. Piv txwv li, kev kis kab mob hauv cov neeg lauscov menyuam yaus nyob ze rau qhov ntawd hauv cov neeg laus [67]. SARS-CoV-acKev kis kab mob tau txuas nrog rau tus lej tuag ntawm 25 feem pua.Thaum cev xeeb tub, muaj qhov tshwm sim ntau ntawm kev rho menyuam tawm spontaneous, tus me nyuam ua ntej, thiab ncua kev loj hlob ntawm lubintrauterine me nyuam tsis muaj kab mob perinatal SARS-CoV[18].

Cov neeg laus uas kis tus kab mob MERS-CoV tuaj yeemtxhim kho ntau yam kab mob thiab kab mob hnyav, los ntawmasymptomatic rau me ntsis, nruab nrab, los yog hnyav (Fig.4) [68]. Lub sij hawm ntawm incubation yog los ntawm 2 mus rau 14 hnub. Qib qisua npaws, hnoos, mob caj pas, hnoos qhuav, thiab myalgiatuaj yeem tshwm sim hauv cov neeg mob me me. Cov neeg mob nrogmob hnyav muaj mob ntsws ntsws Syndrome ntawmmob ua pa, ntau yam txheej txheem hauv nruab nrog cev tsis ua haujlwm, thiabkab mob. Tsis tas li ntawd, cov neeg koom tes ntsuas pneumonia txoj kev loj hlob los ntawm qhov qhab nia ntawm lub hauv siab x-ray lub ntswsthaj chaw nyob rau hauv cov neeg mob uas muaj tus kab mob loj, qhia abruptkev loj hlob tom qab kwv yees li xya hnub thiab mob hnyavmob ntsws o. Cov tsos mob tau nce siab tom qab tom qab ntawdkaum plaub hnub. MERS-CoV muaj ntau dua nyob rau hauv lub ntswscov kab mob ntawm cov kab mob ntau dua li cov kab mob ua pa sab saudcov qauv. Tsis tas li ntawd, cov yam ntxwv extrapulmonary muaj ntau, suav nrog myalgia. Rov qab mus rau ib nrab ntawm tag nrho MERS-CoVcov neeg mob, ib feem peb ntawm cov neeg mob hnyav, nrog rau lub plabmob, xeev siab, ntuav, thiab raws plab, tab tom muajmob raum mob. Ib feem peb yog gastrointestinal, thiabMERS-CoV in stool can be found [68].

Hais txog COVID-19 qaug zog thiab hnoos yog myalgialos yog nkees [69], feem ntau tshaj tawm cov tsos mob.Kev cia siab, mob taub hau, hemoptysis, thiab raws plabCov tsos mob tsawg dua [70, 71], thiab ntau dua ib nrabcov neeg mob, dyspnea tsim (Fig.4). Cov txiaj ntsig ntawmCov ntshav kuaj pom tias cov cell dawb thiab lymphopeniatau li qub los yog txo [72]. Koj typical ICU admission hauv siab CT duab tau ob sab, ntau lub lobular, thiabsub-segment consolidation thaj chaw [73]. Cov neeg mob uas tsis yog ICUpom ob sab av-iav opacity thiab sub-segmentalconsolidation thaj chaw los ntawm tus neeg sawv cev hauv siab CTcov lus xaus [74]. Laboratory kev tshawb fawb pom tias feem ntauCov tsos mob nquag yog hnoos (67.7 feem pua), thiab kub taub hau (87.9 feem pua)thaum raws plab tsis tshua muaj.. 82.1 feem pua ​​​​ntawm ICU tau txaisCov neeg mob tau tshaj tawm lymphopenia [75].

Kab mob sib kis

Qhov tseeb ntawm kev mob kis thoob qhov txhia chaw thiab kev tuag los ntawm1918 tsis paub vim mob npaws tsis txawv lilwm yam kab mob ua pa yam tsis tau kuaj pom [76]. Cov kev kuaj mob hauv lub cev soj ntsuam feem ntau yog cov ntswscov ntaub so ntswg ntawm cov neeg tuag uas tuag nyob rau lub caij nplooj zeeg ntawm1918 [77]. Kuj tseem muaj cov ntsiab lus tsis muaj kabmob kis.Te fu tsis yog ib tus kab mob uas yuav tsum tau soj ntsuamua ntej muaj kev sib kis thoob plaws hauv ib lub xeev lossis tsoomfwv cov pej xeemlub koom haum noj qab haus huv. Tom qab tus kab mob kis thoob qhov txhia chaw tuagpom meej nyob rau lub caij nplooj zeeg xyoo 1918, Tsis tas li ntawd, cov zej zogpib muaj lub cev rog los sau npe cov ntaub ntawv ntawmmob npaws [78]. Txawm li cas los xij, ntau qhov xwm txheej tau zam kev tshaj tawm kev ntseeg siabthiab/lossis tshaj tawm raws sijhawm. Hauv Tebchaws AsmeskasHealth Journal ntawm Lub ib hlis ntuj 1919, tus editor sau nyob rau hauvob peb kis uas cov ntaub ntawv tsis tiav thiab dagvim "qhov kev thov rau kev cuam tshuam tau muaj zog heev, uastsawg tsawg tau kam tsom mus rau kev tshawb fawb yav tom ntej[60]. Tshaj tawm txij li nruab nrab ntawm lub xyoo pua kaum yim,Cov kab mob sib kis tseem ceeb tau tshwm sim nyob nruab nrab ntawm 10 thiab40 xyoo. Ntawm cov no, kev sib kis ntawm "Spanish fu" hauv xyoo 1918yog qhov phem tshaj plaws hauv ntiaj teb, tua 20-40 lab lossis ntau duaneeg (Fig.5) [79].

Xyoo 2002 muaj tus kab mob SARS tshwm sim hauv Guangdong hauvTuam Tshoj ua rau muaj tus kabmob kis loj thib ibntawm lub xyoo pua nees nkaum, nrog rau 916 tus neeg tuag ntawm ntau dua8098 tus neeg mob hauv 29 lub tebchaws. Kaum xyoo tom qab, 2254 lub chaw kuaj mob tau tshaj tawmcase of MERS-CoV was declared by theWHO, nrog 800 tus neeg tuag hauv 27 lub tebchaws, txij xyoo 2012 txog 16Cuaj hlis 2018 [80] (Fig.5). Qhov tseem ceeb, tshaj yim caumfeem pua ​​ntawm cov kev tshawb fawb tsis ntev los no hauv virology thiab noob caj noob ces ntawm noKev kis mob tau pom tias ob qho tib si MERS-CoV thiabSARS puav tuaj yeem yog cov dej muaj peev xwm. ntawm paub meejCov neeg mob SARS, 22 feem pua ​​​​yog cov neeg ua haujlwm noj qab haus huv hauvTuam Tshoj thiab ntau dua 40 feem pua ​​​​yog cov neeg ua haujlwm noj qab haus huv hauvCanada [81]. Ib yam li ntawd, MERS nosocomial kisyog nyob rau hauv Middle East thiab nyob rau hauv Kauslim. Cov xwm txheej tau tshaj tawmnyob rau hauv Middle East thiab North Africa tau pab txhawbmus rau kev sib kis hauv lwm lub tebchaws thiab lawv kisvim kev mus txawv tebchaws. Ob leeg SARS thiab MERSpab txhawb rau pej xeem kev noj qab haus huv thiab nyiaj txiag loj

kis mob [80].

Cov xwm txheej muaj feem cuam tshuam txog kev mob kis thoob qhov txhia chawthiab kev tuag variations

Immunopathology thiab Immunopathology

Dendritic cells (DCs) ua rau muaj txiaj ntsig zookev tiv thaiv kab mob thiab tuaj yeem pib ntau ntawm chemokinesthiab cytokines [82]. Cov hlwb no tuaj yeem txav mus rau lymphoidcov ntaub so ntswg los ntawm peripheral cov ntaub so ntswg los qhib lub populations ntawm T-cells [83]. Ntawm qhov tod tes, tus yuam sij rauKev tiv thaiv kab mob tiv thaiv kab mob yog qhov hloov kho T hlwb[84]; CD4ntxivT hlwb pab txhawb cov kab mob tshwj xeeb antibodyntau lawm los ntawm T-dependent activation ntawm B hlwb [85]. "CD8ntxivT cells" txawm li cas los xij yog cytotoxic, tua kab mob[86]. 

Kev tiv thaiv kab mob hauv lub cev thaum lub sijhawm mob khaub thuas tuaj yeemtxhais tau tias yog kev sib tham sib ntawm mucosal secretionsthiab virions, kab mob epithelial-cell, thiab ua kom muaj zogntawm lwm hom neeg nyob ntawm lub epithelium los yog sub-epithelial txheej [87]. Uas koom nrog lymphoid "innate" hlwb,nyob rau hauv macrophages, thiab dendritic hlwb (xws lialveolar macrophages) [87]. Tom qab cov ntshav yog recruitedmus rau qhov chaw kis kab mob, lwm yam xov tooj ntawm tes zoo li poly-morphonuclear leukocytes thiab monocytes ua haujlwm [88]. Txhua hom ntawm tes qhia tau hais tias muaj ntau yam sib txawv, lawv tuaj yeem ua taurhiab tus kab mob muaj nyob thiab ua kom muaj kev tiv thaiv tshwj xeebkev ua haujlwm.

Tsis tas li ntawd, cov receptors yog nyob rau hauv lub tswv yimntau subcellular Cheebtsam xws li cell membranes,endosomes, cytosol, thiab mitochondria [89]. Qhov no tso caitus tswv tsev rau mount defenses tailored rau invadingpathogen thiab coj nws tropism, intracellular txoj kev ua neej,thiab kev tsim tawm tswv yim rau hauv tus account [90]. Rau futhiab lwm yam kab mob, yog li ntawd, innate teb yuavtau yooj yim muab faib rau hauv modules, txhua yam uasNws suav nrog cov xov tooj tshwj xeeb, receptors, molecules ntawmcov defectors, thiab intracellular compartments. CovCheebtsam ntawm tus mob khaub thuas module enclose (1) solvable extracellular proteins uas muaj corporal kua; (2)qhov system interferon; (3) ntau hom cytokinesthiab chemokines muaj peev xwm orchestrate ib innate teb;(4) macrophage thiab neutrophils phagocytosis; (5) dendriticcell antigen nthuav qhia [91].

Nyob rau hauv cov ntaub ntawv ntawm tus kab mob SARS, Raws li lub innate thiabtau txais cov tshuaj tiv thaiv kab mob pab tswj cov kab mobthiab mob me me, cytokine dysregulation, kab mob cytopathic tsos mob, ACE 2 lub ntsws downregulation, irregularkev tiv thaiv kab mob, thiab cov txheej txheem autoimmuneua rau muaj mob hnyav dua thiab tuag thaum kawg, lubKev nce qib ntawm SARS tuaj yeem txuas nrog cell-mediatedKev tiv thaiv los ntawm T-helper (T1) thiab inflammatoryhyper-innate teb [92]. 

Kev txhim kho tseem ceeb hauv "T1 thiab inflammatorycytokines (interferon-g [IFN-g], interleukin -1 [IL-1],IL-6, thiab IL-12), nrog rau qhov tseem ceeb nce ntxivchemokines zoo li T1 chemokine, IFN-g, IL-10 inducible,(IP-10) neutrophil chemokine, thiab monocyte protein-1chemokine attractions tau pom dua ob lub lis piamtom qab qhov pib ntawm tus kab mob nyob rau hauv ib txoj kev tshawb fawb tau uahauv 20 tus neeg laus kis tus kab mob SARS-CoV [18].

Cov txheej txheem tiv thaiv kab mob los ntawm MERSCoV infections and immune evasion strategies havetseem tsis tau tshawb nrhiav tag nrho. Ntawm kev txaus siab,MERS-CoV evolved innate immunity control strategiesthiab tiv thaiv lossis thaiv txoj hauv kev ntawm IFN ntau lawm [93]. Cov txuj ci no tuaj yeem ua lub luag haujlwm tseem ceebqhov kev tuag siab ntawm cov neeg mob MERS-CoV, tshwj xeebcov uas tsis muaj zog tiv thaiv kab mob. Ib zaug tus kab mobtau raug lees paub tias yog Tus Xov Tooj Zoo Li Tus Txais (TLRs), ib qhontawm ob qhov sib txawv adapter molecules yog recruited tog twg losMyD88 (Myeloid Difference Primary Response 88) los yogTus xov tooj / Interleukin -1 Receptor-(TIR-) domain-muajAdapter-Inducing Interferon- (TRIF). Cov moleculeskuj qhib txoj hauv kev MAPK thiab NF-ŚB uas txhawb nqatxoj kev loj hlob ntawm pro-inflammatory retardantsthiab IFNs "93].

Thaum kis tus kab mob COVID-19 ob leeg yug los thiab yoog rawsLub cev tiv thaiv kab mob yog synergistically koom nrog hauv cov tshuaj tiv thaiv kab mobteb. Tus nqi ntawm lymphocytes thiab subsets ntawm Tcov hlwb uas ua lub luag haujlwm tseem ceeb hauv kev tswj lub cevteb txawv nrog tej yam kab mob pathological mechanismsnyob ntawm hom kab mob. Ib qho kev nce siabnyob rau hauv lub neutrophils, leukocytes, thiab neutrophil-lymphocytepiv (NLR) tau pom nyob rau hauv cov mob hnyav ntawm COVID-19piv rau cov mob me [96]. Qhov tseem ceeb lymphopenia,uas qhia txog kev puas tsuaj ntawm lub cev tiv thaiv kab mob,tshwm sim nyob rau hauv feem ntau cov neeg mob nrog COVID-19, tshwj xeeb tshaj yog nyob rau hauvmob hnyav [97]. Yog li ntawd, nws pom tias leukocytesthiab neutrophils yuav ntxiv dag zog rau cytokine cua daj cua dub (CS)lwm yam uas tsis yog COVID-19 lymphocytes.Kev ua haujlwm dhau los tau txo qis tag nrho cov lymphocytesthiab T cells hauv cov neeg mob SARS-CoV [94]. Te kis los ntawm SARS-CoV-2 tuaj yeem ua rauKev tiv thaiv kab mob dysregulation los ntawm kev cuam tshuam rau T cellsubsets [95–97]. Qhov tseem ceeb T cell alleviation tau pomhauv COVID-19 thiab hais tau ntau dua nyob rau hauv cov mob hnyav.Hauv COVID-19 cov neeg mob, qib cell (CD3ntxiv,,cd8 uantxiv), cytotoxic suppressor thiab pab T hlwb (CD4ntxiv,, CD3ntxiv), thiab tswj T hlwb qis dua li ib txwm muaj. HauvPiv txwv li, pab T hlwb thiab tswj T hlwb zoo kawg liqis dua hauv cov neeg mob hnyav dua li cov neeg mob tsis hnyavraws li qhia hauv Fig.6 [98]. Regulatory T cells paub tias yoglub luag hauj lwm los tswj lub cev tiv thaiv kab mob homeostasis los ntawm suppressingkev ua kom, proliferation, thiab pro-incantatorykev ua haujlwm ntawm feem ntau cov lymphocytes, suav nrog NK hlwb, Tcell CDntxiv4, T-cell CDntxiv8, thiab B cell (Fig.6) [99]. Tsis tas li ntawd,Qhov feem pua ​​​​ntawm cov neeg pab tsis tau T hlwb ua kom muaj zog.

Hauv qhov sib piv, qhov feem pua ​​​​ntawm kev nco pab T hlwbthiab CD28ntxivcytotoxic suppressor T hlwb txo qis hauvmob hnyav COVID-19 cells [100]. Koj tshuav ntawm covNaive T hlwb thiab lub cim xeeb T hlwb yog qhov tseem ceeb raulub cev tiv thaiv kab mob zoo. Dhau li ntawm T cell, txo qisntawm NK hlwb thiab B hlwb raug soj ntsuam hauv COVID-19 [101]. Zuag qhia tag nrho, cov txiaj ntsig no qhia tias SARS-CoV-2 indiqhia tias SARS-CoV-2 yog lub luag haujlwm rau kev tiv thaiv kab mobkev cai nrog induction ntawm aberrant cytokine thiabChemokine teb [102], thiab hloov pauv ntawm lymphocyte subgroup, tag nrho cov uas tuaj yeem ua rau cytokine cua daj cua dubthiab ntxiv cov ntaub so ntswg puas [103]. Tshaj inflammatoryteb nrog tus yam ntxwv ntawm cytokine cua daj cua dub ua raumob hnyav thiab ua rau tus kab mob COVID-19 zuj zus[104].

Hnub nyoog

Lub hnub nyoog ntawm tus neeg cuam tshuam ua lub luag haujlwm tseem ceeb hauv kev txheeb xyuaslawv txoj kev pheej hmoo ntawm kev tuag thaum xyoo 1918 mob khaub thuaskev kis kab mob mus thoob. Feem ntau, thaum lub caij mob khaub thuas tuagcov nqi yog npaj raws li kev ua haujlwm ntawm lub hnub nyoog ntawm cov pejxeem,ib qho "U" tsim nkhaus yog tau, nrog rau qib siab tshaj ntawmkev tuag pom ntawm cov hluas thiab cov laus [6]. Hloov pauv, kev sib kis kis thoob qhov txhia chaw (rau qhov sib txawv) yogcharacterized los ntawm kev hloov hauv lethality mus rau cov hluaspab pawg. Qhov no tau tshwj xeeb yog cim thaum xyoo 1918Kev kis thoob plaws thaum cov hluas (15-30 xyoo) feem ntau muajib tug siab tuag tus nqi uas ib tug "W" mortality nkhaus yog generated [6]. Rau SARS, Cov tib neeg ntawm txhua lub hnub nyoog tau kis tus kab mob, thiab covhnub nyoog nruab nrab yog tsawg dua plaub caug tsib xyoos. Kev kho mobcov neeg ua haujlwm sawv cev 22 feem pua ​​​​ntawm tag nrho cov xwm txheej hauv Hong Kong thiab22.8 feem pua ​​​​hauv Guangdong. Hauv Canada thiab Singapore, feem puantawm cov neeg ua haujlwm kho mob cuam tshuam ntau dua, ntawm 43 feem puathiab 41 feem pua, feem. Lub hnub nyoog thiab poj niam txiv neej faib ntawmSARS hauv Hong Kong yog raws li hauv qab no: 61.7 feem pua ​​​​ntawm cov neeg mob yoghnub nyoog qis dua 45 xyoos, 21.2 feem pua ​​​​yog nyob nruab nrab ntawm 45 thiab 64 xyoohnub nyoog, thiab cov seem muaj hnub nyoog tshaj 64 xyoo. Kaum ib(8.14 feem pua) ntawm 135 lub zej zog thaum ntxov uas tsis muaj nwsTory ntawm kev sib cuag nrog cov neeg mob SARS yog hom zoonotic.Tus neeg tuag nyob hauv Hong Kong nce nrog hnub nyoog zoo li lwm yamCov cheeb tsam hauv ntiaj teb: 14.7 feem pua ​​​​ntawm cov neeg qis dua 44, 21.4 feem puanruab nrab ntawm 45 thiab 64, thiab 63.9 feem pua ​​​​ntawm 64. Kev paub los ntawmHong Kong thiab lwm thaj chaw qhia tias muaj neeg tuagtxuas nrog cov kab mob uas muaj nyob hauv cov neeg laus tshaj plaws(>64 xyoo) [105].

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