Puas yog SARS-CoV-2 Infection Lead To Neurodegeneration And Parkinson's Disease? Ntu 3

Lwm qhov ua tau ntawm inducing PD yuav yog kab mob neurotropism uas ua rau tsis muaj kev puas tsuaj rau cov neuronal hauv thaj chaw muaj tswv yim. IPSC-derived midbrain dopaminergic neurons tau pom tias muaj kev cuam tshuam rau SARS-CoV-2 kab mob, uas ua rau muaj kev mob tshwm sim thiab tom qab cellular senescence hauv vitro [89].

Cellular senescence yog ib qho ntawm cov txheej txheem ntawm tib neeg lub neej uas tsis tuaj yeem zam. Thaum peb muaj hnub nyoog, peb lub cev thiab lub hlwb maj mam muaj hnub nyoog. Txawm li cas los xij, ib qho kev txhawj xeeb loj tshaj plaws yog seb puas nco ploj thaum lub hnub nyoog hlwb.

Txawm hais tias muaj hnub nyoog muaj feem cuam tshuam rau kev nco, nws tsis tau txhais hais tias kev laus ntawm tes yuav ua rau amnesia ncaj qha. Kev nco muaj feem xyuam rau ob lub hlwb qauv thiab kev ua haujlwm, nrog rau yam xws li ib puag ncig, kev ua neej, thiab kev nyiam ntawm tus kheej.

Kev tshawb fawb ntawm cov neeg nyob ntev tau pom tias lawv lub cim xeeb zoo dua li cov neeg nruab nrab. Qhov no yog vim muaj coob tus neeg nyob rau hauv lub neej ntev tau tsim kev ua neej nyob zoo, tswj tus cwj pwm zoo, thiab tib lub sij hawm tau ntsib ntau txoj kev ua neej thiab kev kawm, uas tau muaj txiaj ntsig zoo rau kev saib xyuas kev nco.

Tsis tas li ntawd, cov neeg zoo tib yam kuj tuaj yeem siv ntau txoj hauv kev los ncua kev cuam tshuam ntawm cell aging ntawm lub cim xeeb. Nov yog qee txoj hauv kev los ua nws:

1. Kev tawm dag zog koj lub cev thiab lub hlwb: Kev tawm dag zog lub cev thiab kev cob qhia lub hlwb tuaj yeem ua rau lub hlwb muaj zog thiab cov ntshav ncig, thiab ua rau qeeb ntawm cov cell aging thiab kev txawj ntse poob.

2. Nyob zoo: Nyob zoo, paub txog koj lub peev xwm, thiab lees txais cov kev paub tshiab thiab cov kev sib tw tuaj yeem ua rau koj lub hlwb cov neurotransmitters thiab ua haujlwm ntau dua.

3. Ua kom noj qab nyob zoo thiab pw tsaug zog: Kev noj zaub mov kom zoo, lub teeb, thiab noj qab nyob zoo thiab pw tsaug zog txaus yog qhov tseem ceeb heev los tswj kev ruaj ntseg thiab kev ua haujlwm ntawm lub hlwb.

4. Kev ua si hauv zej zog: Kev sib txuas lus, kev sib txuas lus, thiab kev sib tham thiab kev paub txog lub neej nrog rau lwm tus tuaj yeem txhawb lub hlwb tseem ceeb thiab txhim kho tib neeg lub siab lub ntsws, yog li muaj txiaj ntsig zoo rau kev saib xyuas kev nco.

Feem ntau, txawm hais tias kev laus ntawm tes yog qhov tsis muaj tseeb, peb tuaj yeem ncua nws qhov cuam tshuam rau kev nco los ntawm kev ua neej nyob, kev xav, kev noj haus, thiab kev ua ub ua no, kom muaj kev noj qab haus huv thiab ua haujlwm zoo hauv lub neej ntev. Txoj sia nyob. Nws pom tau tias peb yuav tsum txhim kho kev nco. Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub ntxiv los txhim kho kev nco

RNA-sequencing tsom xam ntawm ventral midbrain cov ntaub so ntswg ntawm COVID-19 cov neeg mob tau qhia ib qho piv txwv phenotypeof inflamed neurons thiab txheeb xyuas cov qib qis ntawm SARS-CoV-2 transcripts [89]. Cov ntaub ntawv no tau hais tseg tias tej zaum yuav muaj kev cuam tshuam tshwj xeeb rau SARS-CoV-2 ntawm thaj chaw tshwj xeeb ntawm cov hlab ntsha nruab nrab cuam tshuam nrog kev txhim kho PD.

Qhov kev cuam tshuam dav dav ntawm lub hauv nruab nrab lub paj hlwb cov qauv rau SARS-CoV-2 tau qhia los ntawm Ramani li al., leej twg kis mob hlwb organoids thiab pom cov kab mob nkag mus, tshwj xeeb tshaj yog inneurons. Tus kab mob no ua rau muaj kev hloov pauv thiab hyperphosphorylation ntawm tauand tom qab neuronal tuag [90].A txuas ntawm NF-κB thiab PD tau tsim yav tas los vim NF-κB tau nce hauv substantia nigra ntawm MPTP-kho nas [91].

MPTP kev kho mob yog ib hom tsiaj ntawm PD raws li cov neurotoxin ua rau nigrostriatal degeneration thiab poob ntawm dopaminergic neurons [91,92]. Kev txwv NF-κB hauv cov qauv no coj mus rau kev tiv thaiv ntawm kev degeneration ntawm dopaminergic neurons [91]. Hauv ib qho qauv hauv vitro ntawm dopaminergic neurons, kev kho mob nrog 6-OHDA coj mus rau NF-κB ua kom, caspase activation, thiab apoptotic tuag uas tau tiv thaiv los ntawm inhibition ntawm NF-κB [93].

NF-κB yog qhib los ntawm SARS-CoV-2 viapattern recognition receptors, uas tej zaum yuav yog ib tug neurodegenerative trigger [93].Lwm yam nthuav yog qhov cuam tshuam rau cov angiotensin-aldosteronesystem hauv COVID-19 thiab PD.

Angiotensinogen yog tsim los ntawm astrocytes ua ib feem ntawm alocal ywj siab renin-angiotensin system (RAS) [94,95]. Nws pathological overactivation (uas kuj tshwm sim los ntawm degeneration ntawm dopaminergic neurons) ua rau oxidative stressand o, whereas nws inhibition raug suav hais tias yog ib qho kev xaiv kho mob nyob rau hauv ntau cov kab mob neurodegenerative nrog rau PD thiab AD [96,97].

SARS-CoV-2 siv ACE2-receptor raws li kev nkag mus rau hauv cov cell host thiab, yog li ntawd, cuam tshuam nrog RAS ib yam nkaus [10].A yav dhau los pom kev sib txuas ntawm tus kab mob khaub thuas H1N1 thiab -synucleinaggregation tuaj yeem muaj feem cuam tshuam rau SARS-CoV-2, ib yam nkaus. H1N1 coj mus rau kev sib sau ntawm endogenous -synuclein hauv LUHMES hlwb [98].

Raws li qhov laj thawj rau kev sib sau ua ke ntawm pathological synuclein tom qab kis kab mob H1N1, qhov kev puas tsuaj ntawm autophagosome ntawm cov kab mob LUHMES-hlwb tau raug npaj [98]. Interestingly, -synuclein aggregates kuj pom nyob rau hauv olfactory noob tom qab intranasal instillation ntawm H1N1 [98].Cov tsos mob ntawm PD yog olfactory thiab vegetative dysfunction nrog rau obstipationas thiab prodromal syndrome REM pw tsaug zog cwj pwm tsis zoo (RBD).

Olfactory dysfunction yog ib qho kev mob tshwm sim ntxov heev ntawm COVID-19, thiab txoj kev olfactory tau tham txog ib txoj hauv kev kis tus kabmob mus rau CNS [21,26]. Yog li ntawd, nws zoo li qhov tseeb tias COVID-19 tuaj yeem cuam tshuam cov kab mob ntawm PD raws li SARS-CoV-2 tuaj yeem siv txoj hauv kev sib kis uas tau piav qhia rau kev txhim kho neuropathology hauv PD [99,100].

Kev tshawb nrhiav Polysomnographic hauv 11 tus neeg mob plaub lub hlis tom qab pib kis mob nrog SARS-CoV-2 tau nthuav tawm lub sijhawm ntawm REM pw tsaug zog tsis muaj atonia hauv 4 tus neeg mob, uas yog acharacteristic (prodromal) kos npe ntawm RBD [101].

Lwm qhov nthuav yog qhov kev loj hlob ntawm PD yog txuas nrog lub plab microbiome thiab nws cov dysbiosis [102]. SARS-CoV-2 ua rau muaj kev tsis sib haum xeeb ntawm plab microbiome (dysbiosis) thiab plab hnyuv o uas qhia los ntawm fecal calprotectin elevated fecal calprotectin hauv COVID-19- mob raws plab, uas tawm tswv yim txuas mus rau PD [103,104]. SARS-CoV-2 RNAwas kuaj pom nyob rau hauv cov quav li ntawm 50% ntawm cov neeg mob uas muaj tus kab mob COVID-19, txhawb cov kev xav ntawm kev mob plab hnyuv [105].

Kev tshawb nrhiav molecular tau tsim kev sib txuas ntawm COVID-19 thiab PD tsom rau kev sib cuam tshuam ntawm cov protein. Nyob rau hauv tag nrho, 44 ​​cov proteins hauv CNS cuam tshuam hauv PD tau pom muaj kev cuam tshuam nrog 24 tus tswv tsev cov proteins los ntawm lub ntsws uas cuam tshuam nrog SARS-CoV-2 cov kab mob kis kab mob [106].Qhov ob tus neeg sib tw muaj txiaj ntsig zoo tshaj plaws yog Rab7a thiab NUP62 [ 106] ib. Rab7a yog alysosomal protein txo qhov kev faib ua feem ntawm cov hlwb nrog -synuclein hais nrog rau cov tshuaj lom ntawm -synuclein, whereas NUP62 koom nrog hauv autophagosome tsim [106].

Qhov kev sib piv ntawm transcriptomic modulations induced los ntawm SARS-CoV-2 thiab PD kuj tau nthuav tawm qhov tseem ceeb sib tshooj hauv ntau txoj hauv kev [107]. Ntawm qhov tod tes, lub luag haujlwm tiv thaiv ntawm -synuclein tiv thaiv COVID-19 tau tshaj tawm txij li -synuclein, zoo li -amyloid, yog upregulated nyob rau hauv lub ntsej muag ntawm tus kab mob kis thiab muaj peev xwm txwv tsis pub tus kab mob replication ua ib tug tiv thaiv mechanism nyob rau hauv lub hlwb [108].

Qhov no ua rau muaj kev xav tias PD cov neeg mob uas muaj ntau dua -synuclein hauv lub hlwb yuav muaj kev tiv thaiv qee yam tiv thaiv SARS-CoV-2 kab mob [109]. Ua ntej tus kab mob COVID-19 muaj thoob qhov txhia chaw, ib qho kev tshawb fawb txog kev rov qab los ntawm Nyij Pooj tau pom tias cov neeg mob PD hauv tsev kho mob tsawg dua li lwm tus neeg mob tuag los ntawm mob ntsws [109].

Yog tias tus kab mob kis tau ua rau muaj kev tswj hwm ntawm -synuclein raws li kev tiv thaiv kev tiv thaiv, nws tuaj yeem ua rau lub sijhawm ntev o thiab neuronal tuag ua rau kev txhim kho ntawm PD nyob rau lub sijhawm ntev raws li tau qhia ua ntej rau West Nile tus kab mob kis [87].

Qhov zoo siab, qhov kev xav tsis zoo ntawm kev sib txuas ntawm COVID-19 thiab atypical parkinsonism tuaj yeem tsim tau ib yam, txawm hais tias cov ntaub ntawv ntawm cov ncauj lus no tsis tshua muaj los txog tam sim no. Nws tau pom tias atypical Parkinson's syndromes xws li multisystem atrophy thiab kev loj hlob ntawm tus kab mob supranuclear palsy yog txuam nrog microglial activation raws li ib tug kos npe rau ntawm neuroinflammation thiab hais tias lub microglial activation pab mus rau kev loj hlob ntawm neurodegeneration [110-112].

Tsis ntev los no, nws tau pom tias kev ua kom microglial tuaj yeem pom los ntawm PET duab, uas yuav ua haujlwm ua biomarker rau tauopathies [113,114]. Microglial activation thiab neuroinflammation tau pom hauv COVID-19 raws li tau piav qhia hauv Tshooj 1, tsim kev sib txuas ntawm atypical parkinsonism thiab COVID-19 [39].

5.3. Alzheimer's Disease, Cognitive Deficits thiab COVID-19

Muaj cov ntaub ntawv pov thawj uas qhia tau tias muaj kev sib raug zoo ntawm kev paub tsis meej thiab COVID-19. Txoj kev tshawb nrhiav ntev ntev tau qhia tias kev paub txog kev poob qis uas ntsuas los ntawm Montreal Kev Ntsuas Kev Paub Txog Kev Paub (MOCA) tau pom meej hauv 21% ntawm cov neeg mob COVID-19 me me vs. 2% ntawm cov neeg tsis muaj zog [115]. Lwm txoj kev tshawb nrhiav pom pathological MOCA tau tshwm sim hauv 18 ntawm 26 COVID-19 cov neeg mob thiab tseem muaj FDG-PET abnormalities (frontoparietal hypometabolism) hauv 10 tus neeg mob uas sib piv rau kev kho mob tsis txaus [45].

Kev paub txog kev poob qis tsis yog tsuas yog pom thaum muaj tus kab mob hnyav tab sis kuj tseem muaj cov ntaub ntawv qhia txog kev paub tsis meej tom qab rov zoo los ntawm COVID-19, raws li MOCAabnormalities raug kuaj pom nyob rau hauv ib pawg neeg mob tom qab COVID-19 [116]. Lwm qhov kev tshawb fawb tau lees paub tias qhov kev paub tsis txaus ntseeg tau muaj nyob hauv 70% ntawm cov neeg mob COVID-19 tsawg kawg yog 1 lub hlis tom qab tawm hauv tsev kho mob [116,117]. Ib yam li ntawd, 46 ntawm 57 tus neeg mob rov qab los ntawm COVID-19 (81%) muaj cov tsos mob ntawm kev puas hlwb [13,118].

Interestingly, persisting memory and concentration deficits was found after SARS-Cov-1 and MERS infections in 15–20% of case [119].Lwm txoj kev kawm nthuav dav siv transcranial magnetic stimulation los tshawb xyuas COVID-19 cov neeg mob uas tau zoo lawm. raug kev txom nyem los ntawm cov kab mob hnyav nrog ICU nyob thiab cov teeb meem hauv lub paj hlwb qhia txog kev qaug zog thiab qhia cov qhab nia txawv txav hauv lub ntsej muag kev ntsuas roj teeb thaum lub sij hawm subacute [120].

Lub transcranial magnetic stimulation nyob rau hauv cov neeg mob no tau nthuav tawm qhov kev puas tsuaj loj ntawm GABAergic intracortical circuits thaum glutamatergictransmission tsis zoo [120]. GABAergic impairments feem ntau tshwm sim hauv frontotemporal dementia thiab kev ua haujlwm tsis zoo [120,121]. Txawm li cas los xij, nws yuav tsum tau muab sau tseg tias kev paub tsis meej yog ib qho teeb meem tshwm sim tom qab raug mob los ntawm kev mob ua pa nyuaj (ARDS), uas tuaj yeem muaj ntau yam laj thawj uas tsis yog COVID-19 [116,122–124].Tom qab ARDS, kev paub tsis meej nyob rau hauv ntev. -lub sij hawm rov qab los ntawm kwv yees li 10% ntawm cov neeg mob [116,122].

Lwm cov kev tshawb fawb pom pom kev tsis txaus ntseeg thiab kev puas siab puas ntsws (feem ntau yog kev nyuaj siab thiab kev ntxhov siab) txog li 60% ntawm ARDS cov neeg muaj sia nyob tom qab 12 lub hlis [125].Dementia tau pom tias yog ib qho kev pheej hmoo loj tshaj plaws rau COVID-19 thiab cuam tshuam nrog kev tuag ntau dua [126–130]. Cov neeg mob uas muaj dementia muaj teeb meem ua raws li cov cai ntawm kev nyiam huv, daim npog qhov ncauj, cov lus qhia coj tus cwj pwm, thiab cov cai nyob sib nrug vim kev paub tsis meej [124,131].

Cov neeg mob Dementia nquag nyob hauv cov tsev laus uas muaj kev pheej hmoo ntau dua rau kev kis tus kab mob nyob hauv ntau thaj chaw [124].COVID-19 kab mob hauv cov neeg mob dementia feem ntau tshwm sim atypical nthuav tawm foremost withdelirium / tsis meej pem thiab qee cov tsos mob sib kis [129,132]. Kev tsis meej pem thiab kev xav thiab kev coj tus cwj pwm tsis zoo tshwm sim nyob rau hauv 19.2% ntawm cov neeg muaj txoj sia nyob [129].Kev tsom xam ntawm kev sib raug zoo hauv network rau cov noob / cov protein tau teeb tsa ntawm tus kab mob thiab tus tswv tsev nrog rau cov kab mob sib txawv hauv cov qauv kev sib txuas lus tau pom qhov sib thooj ntawm COVID{ {8}} thiab kev txawj ntse poob zoo li ADand PD [13].

Cov kev tshawb fawb Postmortem tau pom tias ACE2 qhia tau nce hauv lub hlwb ntawm cov neeg mob AD. Tshwj xeeb tshaj yog nyob rau hauv dementia hnyav, ACE2 qhia tau nce siab, uas tuaj yeem ua rau muaj kev cuam tshuam ntau dua rau COVID-19 [123,124,133].Ischemic dawb teeb meem puas tsuaj tshwm sim thaum ntxov AD ua rau muaj kev loj hlob ntawm dementia. COVID-19 tuaj yeem ua rau cov kab mob vascular vim hypercoagulability thiab tuaj yeem xav tias yuav ua rau kom muaj kab mob nrawm rau cov neeg mob AD [123,134].

Nws tau xav tias amyloid-, cov protein cuam tshuam rau hauv kev txhim kho AD, isan antimicrobial peptide koom nrog hauv kev sib ntaus sib tua cerebral SARS-CoV-2 kab mob raws li yav dhau los tau piav qhia rau -synuclein hauv PD [123,135]. Nws tuaj yeem xav tias amyloid- yog upregulated raws li kev tiv thaiv mechanism thaum lub sij hawm kis kab mob ua rau muaj overactivation nrog pathological deposition ntawm amyloid- nyob rau hauv ntev [123,135].

Apoε4, qhov tsim muaj kev pheej hmoo rau AD, kuj tau lees paub tias yog ib qho kev pheej hmoo tseem ceeb rau COVID-19, uas muaj feem cuam tshuam rau ob txoj kab mob physiologies [136]. COVID-19 qhov hnyav tuaj yeem raug kwv yees los ntawm Apoε4 genotype [136]. Hauv tib neeg iPSCs qauv nrog Apoε4 genotype, neurons, thiab astrocytes tau raug ntau dua rau SARS-CoV-2 kab mob dua li cov tsis-Apoε4 hlwb thiab hlwb organoids [12].

Lwm qhov taw qhia ntawm kev sib tshooj yog IL-6, uas tau pom tias tau nce siab hauv COVID-19 thiab kuj tseem suav tias yog biomarker nrog tus nqi ntsuas hauv AD [49,123,137].SARS-CoV-2 yog qhov yuav cuam ​​tshuam autonomic functions nyob rau hauv vagal tswj chaw nyob rau hauv lub hlwb [127]. Nyob rau hauv AD, autonomic functions yog impaired ib yam nkaus li, vim hais tias ntau dua cardiacsympathetic muaj nuj nqi thiab qis parasympathetic muaj nuj nqi yog qhia nyob rau hauv cov neeg mob [127].

Yog li ntawd, noninvasive (auricular) vagal paj hlwb stimulation yog tham raws li ib tug kho mob rau AD raws li zoo raws li mob hnyav COVID-19, txij li downregulation ntawm inflammatory pathways (txo ntawm IL-6 qib) yuav tsum tau raws li ib tug tshwm sim [127] . Kev txhawb nqa qhov kev xav no, trans auricular vagal paj hlwb stimulation tau tuaj yeem txo qhov kev xav tsis zoo hauv apreclinical murine qauv ntawm AD [138].

AD ua rau muaj kev hloov pauv hauv calcium homeostasis hauv lub hlwb; Cov kab mob RNA siv cov txheej txheem tib yam los pab txhawb cov kab mob sib kis [124]. Yog li ntawd, cov kab mob sib kis yuav yooj yim dua hauv lub hlwb ntawm cov neeg mob AD qhov twg calcium homeostasis twb txawv txav [124].Muaj kev sib koom ua ke ntawm AD thiab ntshav qab zib hom II, uas ua rau muaj kev pheej hmoo ntawm kev tsim AD [139].

AD thiab ntshav qab zib hom II ob leeg tau pom tias yog qhov muaj feem cuam tshuam rau COVID-19 ua rau muaj kev phom sij rau cov pab pawg neeg mob tshwj xeeb thiab thov kom muaj kev sib txuas ntawm cov kab mob no uas tuaj yeem piav qhia txog kab mob sib tshooj [139].Tau cov lus hauv tsev ntawm Tshooj 3 (Tshooj 5 ):

1. Cov kab mob muaj cov tswv yim sib txawv los tswj hwm lub zog ntawm cov xov tooj ntawm tes, piv txwv li, cuam tshuam autophagy thiab mitochondrial lossis lysosomal zog, uas nws ua haujlwm tsis zoo tau cuam tshuam rau cov kab mob neurodegenerative.

2. Kev hloov pauv neuroinflammatory vim yog COVID-19 xws li nce qib IL-6 lossis ua kom NF-κB tuaj yeem ua rau / nrawm rau kev txhim kho PD.

3. Direct CNS invasion los ntawm SARS-CoV-2 kuj tseem tuaj yeem ua rau muaj kev cuam tshuam ntawm neurodegenerative cascades hauv thaj chaw muaj tswv yim.
4. COVID-19 tuaj yeem ua rau muaj kev tsis txaus ntseeg thiab tsis txaus ntseeg, txawm hais tias qee qhov tuaj yeem yog vim ARDS.

5. Dementia thiab Apoε4 genotype yog qhov muaj feem pheej hmoo rau COVID-19 thiab nws txoj kev tuag.

6. Tshooj 4

Parkinson's Disease thiab COVID-19: Kev cuam tshuam rau PD Cov tsos mob, Kev puas siab puas ntsws thiab kev sib raug zooCov kev cuam tshuam ntawm kev sib kis ntawm lub neej niaj hnub tau loj heev rau tag nrho cov neeg hauv ntiaj teb, thiab cov neeg mob uas muaj kab mob ntev uas xav tau kev saib xyuas tsis tu ncua tau cuam tshuam tshwj xeeb. Kev soj ntsuam dav dav ntawm cov kev tshawb fawb thoob ntiaj teb (210,419 tus neeg koom nrog tag nrho) tau pom tias kev saib xyuas mob rau cov kab mob hauv lub paj hlwb, feem ntau, tau cuam tshuam los ntawm kev sib kis hauv 47.1% ntawm cov neeg mob [140].

Qhov cuam tshuam rau cov neeg mob PD tau piav qhia txawv, raws li cov teeb meem tshwj xeeb tau tshwm sim nrog kev txwv tsis pub muaj kev sib kis. Cov teeb meem puas siab puas ntsws nrog rau kev saib xyuas thiab kev muab tshuaj tau pom tias yog lub nra hnyav tshaj plaws hauv pawg neeg no [140].COVID-19 tuaj yeem hloov pauv cov tshuaj pharmacodynamics ntawm levodopa kuj vim mob plab, uas yog ib qho tsos mob ntawm COVID{{3} } [141] ib. Qhov no ua rau lub cev muaj zog hloov pauv hauv cov neeg mob PD [141]. PD cov neeg mob uas raug kev txom nyem los ntawm COVID-19 feem ntau tshwm sim tom qab-COVID syndrome (85.2%) uas muaj lub cev muaj zog ua haujlwm tsis zoo, nce kev noj tshuaj txhua hnub levodopa, qaug zog, poob siab, thiab pw tsaug zog tsis zoo [142].

Txawm li cas los xij, cov tsos mob tsis zoo ntawm lub cev muaj zog thiab cov tsos mob tsis yog lub cev muaj zog ntawm cov neeg mob uas tsis muaj kab mob PD thaum lub sijhawm muaj kev sib kis kuj tau sau tseg hauv cov kev tshawb fawb sib txawv [143,144].Cov tsos mob ntawm tus cwj pwm tshiab tau pom nyob rau hauv 26% ntawm cov neeg mob PD hauv ib qho Italian cross-sectionalstudy [144] . Cov neeg mob PD tau tshaj tawm tias muaj kev kho siab thiab tsis muaj kev txhawb nqa thiab kev sib txuas lus nrog lawv cov kws kho mob [143].

Nws tau pom tias kev hloov pauv ntawm dopamine-dependent yog qhov yuav tsum tau ua kom muaj txiaj ntsig zoo; Yog li, cov neeg mob PD yog qhov tsis tshua muaj kev hloov pauv thiab tuaj yeem muaj teeb meem ntau ntxiv rau qhov chaw tshiab [145,146]. Yog li, tus kab mob kis thoob qhov txhia chaw tuaj yeem ua rau muaj qhov cuam tshuam ntawm kev ntxhov siab hauv PD cov neeg mob uas raug yuam kom hloov mus rau qhov chaw tshiab sai.

Kev ntxhov siab ntawm lub hlwb tau pom tias ua rau cov tsos mob PD zuj zus ntxiv nrog rau qhov ua tau zoo ntawm cov tshuaj dopaminergic tshwj xeeb tshaj yog nyob rau ntawm qhov tshee [145,147]. Qhov no tuaj yeem yog ib qho kev piav qhia rau cov tsos mob tshwm sim hauv cov neeg mob PD thaum muaj kev sib kis thoob ntiaj teb.Nws tau pom tias 103 PD cov neeg mob tau tshaj tawm plaub qhov teeb meem tseem ceeb hauv thawj Italian kaw: 1. ntshai ntawm kev cog lus corona, 2. txo qis hauv lub cev, 3. tsis tuaj yeem nkag mus. txhawb kev pabcuam thiab chaw kho mob, thiab 4. txo kev sib raug zoo [148]. Muaj qhov txo qis ntawm kev ua lub cev, ntsuas los ntawm daim ntawv thov smartphone, vim tias cov neeg mob PD feem ntau ua tsis tau raws li 30 min ntawm kev ua haujlwm ib hnub [149].

Qhov no tau ua rau hnyav ntxiv hauv 44% thaum lub sijhawm kaw [149]. Nws yog qhov paub zoo tias kev siv lub cev thiab kev cob qhia cov tswv yim kho mob tseem ceeb hauv PD los tswj lub cev muaj zog thiab kev ywj pheej, yog li kev ua haujlwm ntawm lub cev tsis muaj zog thaum lub sijhawm kaw tuaj yeem xav tias yuav ua rau muaj kev mob tshwm sim thiab tsis muaj kev ywj pheej [149].Ntxiv mus, 66% ntawm PD Cov neeg mob nyob rau hauv ib pawg loj ntawm Columbia University tau tshaj tawm txog kev xav thiab kev pw tsaug zog nyob rau hauv lub ntsej muag ntawm kev sib kis; Kev nyuaj siab thiab insomnia yog lawv feem ntau tshaj tawm cov tsos mob ntawm kev puas siab puas ntsws hauv ntau lwm cov kev tshawb fawb thiab [150–154].

Ib txoj kev tshawb fawb Suav tau qhia tias cov neeg mob PD muaj kev pw tsaug zog ntau dua thiab kev ntxhov siab ntau dua li kev tswj hwm kev noj qab haus huv thiab cov tsos mob no tau cuam tshuam nrog kev cuam tshuam ntawm lwm cov tsos mob PD [154]. Cov teeb meem pw tsaug zog kuj tseem cuam tshuam nrog kev ua neej tsis zoo [153]. Cov kev pabcuam hauv siab tau pom tias txo qis kev nyuaj siab thiab ntxhov siab, txhim kho lub cev muaj zog, thiab ntxiv dag zog rau kev ua haujlwm [145]. Raws li qhov no tuaj yeem ua tiav zoo, nws zoo li yog lub tswv yim kho mob muaj txiaj ntsig tam sim no thiab rau yav tom ntej [145].Lub sijhawm saib xyuas tau nce ntau heev thaum muaj kev sib kis.

Kev saib xyuas feem ntau yog muab los ntawm cov neeg hauv tsev neeg [155,156]. Tus neeg saib xyuas lub nra tau nce ntxiv thaum lub sijhawm COVID-19 era [144]. Interestingly, Montanaro et al. thiab lwm tus tau pom tias muaj kev ntxhov siab thiab kev nyuaj siab ntau zaus hauv PD cov neeg mob thiab lawv cov neeg saib xyuas [157,158]. Kev nyuaj siab tau pom 35% ntawm cov neeg mob PD thiab 21.7% ntawm cov neeg zov me nyuam; 39% ntawm cov neeg mob PD thiab 40% ntawm cov neeg zov me nyuam raug kev ntxhov siab [158].

Yog li ntawd, cov neeg saib xyuas yuav tsum tau txais kev txhawb nqa ntxiv, tshwj xeeb tshaj yog nyob rau lub sijhawm muaj tus kabmob kis no los tiv thaiv lawv lub nra thiab cov tsos mob neuropsychiatric ntawm lawv cov txheeb ze [159].Txawm li cas los xij, COVID-19 tsis tsuas yog cuam tshuam rau cov tsos mob PD; nws kuj tau tham txog tias PD uas muaj nyob ua ntej tuaj yeem ua rau muaj kev pheej hmoo ntawm kev tuag lossis kev tuag thaum muaj kab mob SARS-CoV-2 tshwm sim. Cov ntaub ntawv ntawm lub ncauj lus no muaj kev tsis sib haum xeeb (subsumed hauv Table 1).

Kev tshuaj xyuas ntxaws los ntawm Fearon et al. Cov lus suav hais tias COVID-19 kev tuag yog tej zaum tsis muaj ntau ntxiv hauv PD cov neeg mob uas nyiam ua tsis taus pa tsawg dua thaum kis tus kab mob, tau ua tiav asymptomatic ntau dua, thiab tsis tshua xav tau mus pw hauv tsev kho mob [141,160,165–167]. Lub sijhawm ntawm ICU nyob / tsev kho mob thiab tso pa tawm kuj tsis txawv hauv PD thiab tsis yog PD COVID-19 cov neeg mob hauv kev soj ntsuam loj ntawm cov neeg mob German [165]. AnItalian txoj kev tshawb fawb piv rau COVID-19 cov neeg mob nrog PD rau COVID-19 cov neeg mob uas tsis muaj PD thiab pom tsis muaj qhov sib txawv ntawm kev tuag (5.7% ntawm PD COVID-19 cov neeg mob tuag vs. 7.6% ntawm cov neeg tsis yog PDCOVID{{ 16}} cov neeg mob) [160].

Cov qauv no tuaj yeem txhawb nqa los ntawm kev xav tias amantadine thiab entacaponem yuav muaj txiaj ntsig tiv thaiv COVID-19, uas tau pom zoo los ntawm cov kev tshawb fawb sib txawv [172–174]. Txawm li cas los xij, kev tshuaj xyuas tag nrho ntawm 1061 PD cov neeg mob uas tau lees paub COVID-19 tau pom tias muaj tus nqi pw hauv tsev kho mob ntau dua, cov neeg mob tuag, thiab kev tuag rau cov neeg mob no ntau dua li cov neeg mob uas tsis yog PD COVID-19 [175].

Ib qho kev txwv ntawm txoj kev tshawb fawb no yog qhov tsis muaj hnub nyoog sib txuam, uas yuav cuam tshuam rau qhov tshwm sim, vim tias hnub nyoog yog ib qho ntawm cov kev pheej hmoo tshaj plaws rau cov neeg mob tuag thiab kev tuag ntawm COVID-19 [175,176]. Ib qho kev tshawb fawb Asmeskas tau muab piv rau 78,355 tus neeg mob uas tsis yog PD COVID-19 rau 694 COVID-19 cov neeg mob uas muaj PD thiab pom muaj kev tuag ntau ntxiv txawm tias tom qab kho thiab sib piv rau hnub nyoog thiab poj niam txiv neej [169].

Amulticentric German txoj kev tshawb fawb tau pom tias qhov kev nthuav dav thiab kev tuag ntawm COVID-19 tau siab dua PD dua li cov neeg mob uas tsis yog PD [168].Cov ntaub ntawv no tsis suav nrog, thiab cov lus qhia meej txog seb cov neeg mob PD puas muaj kev pheej hmoo ntau dua rau tus mob (mob hnyav) Tus kab mob COVID-19 tsis tuaj yeem ua rau lub sijhawm no. Nws yuav tsum raug sau tseg tias PD cov neeg mob uas raug kev txom nyem los ntawm COVID-19 tus kab mob yuav tshwm sim nrog cov tsos mob atypical xws li lub siab hloov pauv, qaug zog, mob pob qij txha, dej ntws tawm, thiab ua rau cov tsos mob PD ua rau nyuaj, uas tuaj yeem cuam tshuam qhov kev kuaj mob ntawm SARS-CoV{ {6}} kab mob [177].

Nqa cov lus hauv tsev ntawm Tshooj 4 (Tshooj 6): 1. Tom qab-COVID-sydrome, hloov pauv pharmacodynamics ntawm levodopa, thiab ua rau cov tsos mob ntawm lub cev muaj zog yog tshwm sim nyob rau hauv cov neeg mob PD nrog COVID-19.2. Txawm tias cov neeg mob PD uas tsis muaj kab mob no feem ntau raug kev txom nyem los ntawm cov tsos mob ntawm lub cev muaj zog thiab tsis yog lub cev muaj zog, txo qis kev ua haujlwm ntawm lub cev, nrog rau kev ntxhov siab, kev ntxhov siab, thiab kev nyuaj siab.3. Txawm hais tias PD nce qhov kev pheej hmoo ntawm COVID-19 kev tuag tseem tsis tau paub meej, txij li cov ntaub ntawv ntawm cov ncauj lus no tsis suav nrog.

7. Cov lus xaus

Cov ntsiab lus nthuav tawm hauv qhov kev tshuaj xyuas no qhia meej tias COVID-19 muaj kev cuam tshuam rau paj hlwb/neurological. Txawm hais tias SARS-CoV-2 tuaj yeem nkag mus rau CNS thiab cuam tshuam ncaj qha rau neuronaldamage lossis seb cov tsos mob ntawm lub paj hlwb puas yog vim qhov cuam tshuam thib ob tsis tuaj yeem ua rau muaj qhov tseeb. Kev cuam tshuam ntawm tus kab mob ntawm cov kab mob neurodegenerative tseem tsis tau meej meej, tab sis ntau yam kev xav ntawm pathophysiological muaj txuas nrog COVID-19 toneurodegeneration thiab ua rau nws tshwm sim tias tus kab mob kis thoob qhov txhia chaw tuaj yeem muaj kev cuam tshuam rau cov kab mob neurodegenerative xws li AD thiab PD.

Tib yam tau npaj rau lwm qhov kev kis kab mob yav dhau los, txawm hais tias qhov tseeb tshwm sim / nrawm ntawm cov kab mob ntawm cov kab mob neurodegeneration tsuas tuaj yeem pom tau rau qee tus kab mob xws li HCV thiab HIV txog tam sim no. Kev saib xyuas cov neeg mob rov zoo los ntawm COVID-19 tshwj xeeb tshaj yog cov neeg mob uas muaj kab mob neurodegenerative thiab COVID-19 vam tias yuav teb qee cov lus nug no yav tom ntej. Xws li kev tshawb nrhiav yav tom ntej tseem txwv tsis pub muaj peev xwm kawm ntxiv txog cov kab mob neurodegenerative pathophysiology thiab tsim cov tswv yim tshiab rau kev kho mob-hloov kho.

Sau Kev Koom Tes: Kev Ntseeg: LK; kev sau ntawv-thawj daim ntawv npaj: LK; sau-saib thiab kho kom raug: FW, GUH thiab MKH; Kev pom zoo: MKH Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.

Kev Pab Nyiaj: LK tau txais kev txhawb nqa los ntawm PRACTIS-Clinician Scientist Program ntawm Hannover Medical School, tau nyiaj los ntawm German Research Foundation (DFG, ME 3696/3-1). Txwv tsis pub, qhov kev tshawb fawb tau txais nyiaj txiag sab nraud.

Institutional Review Board Statement: Tsis siv tau.

Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.

Cov ntaub ntawv

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