Neurological manifestations of COVID-19

SARS-CoV-2 virus, koji uzrokuje bolest COVID-19, pripada porodici koronavirusa, heterogenoj skupini ovijenih, jednolančanih, pozitivno usmjerenih RNA virusa. Koronavirusi imaju najveći genom među RNA virusima, a virusna RNA posjeduje 4 do 5 gena koji kodiraju strukturne proteine, uključujući glukoprotein korona-izdanka (S protein) putem kojeg virus inficira ciljnu stanicu. Osnovni način ulaska SARS-CoV-2 u stanice ljudskog domaćina jest vezanjem virusnog S proteina za angiotenzin-konvertirajući enzim 2, koji je izražen na stanicama brojnih tkiva, uključujući i živčano. SARS-CoV-2 sedmi je poznati humani koronavirus, nalik na određene viruse iz porodice koronavirusa, ali i druge respiratorne viruse, koji pokazuje svojstva neuroinvazivnosti i neurotropizma. Izravno oštećenje neurona virusom obično vodi u programiranu staničnu smrt. Zahvaćanje stanica glijalnog sustava očituje se pretjeranom reaktivnošću glijalnih stanica što pogoduje razvoju neurodegenerativnih promjena. Izravan utjecaj virusa na neurone i glijalne stanice zahtjeva sposobnost neuroinvazivnosti. Postoje dva osnovna puta prodora SARS-CoV-2 virusa u središnji živčani sustav, a to su hematogeni i neuralni put. Osim izravnih oštećenja virusom, uzrok neuroloških manifestacija bolesti COVID-19 mogu biti i neizravni mehanizmi, kao što su sistemski upalni odgovor na infekciju, razvoj autoimunosti te hipoksična ozljeda mozga. Navedeni mehanizmi uzrokuju širok spektar neuroloških manifestacija bolesti COVID-19. Neurološki se poremećaji mogu javiti bez drugih priležećih simptoma, ali i u teškim oblicima bolesti COVID-19, kada su povezani sa znatno višom stopom mortaliteta. Također, smatra se kako bi infekcija SARS-CoV-2 virusom u određenog broja zaraženih mogla dovesti i do dugoročnih, neurodegenerativnih promjena. S obzirom da je COVID-19 nova bolest, istraživanja i spoznaje o povezanosti SARS-CoV-2 virusa i živčanog sustava tek slijede.SARS-CoV-2, the causative agent of COVID-19, belongs to a family of coronaviruses, a heterogenous group of enveloped, single stranded, positive sense RNA viruses. Coronaviruses have the largest genome among RNA viruses and viral RNA possesses 4 or 5 genes encoding structural proteins, including spike glycoprotein (S protein) through which virus infects targeted cell. To enter the human host cells, S protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2, which is expressed on cells of various tissues, including the nervous one. SARS-CoV-2 is the seventh known human coronavirus and like some other members of coronaviruses family, but also other families of respiratory viruses, it shows signs of neuroinvasivity and neurotropism. Direct viral neuronal injury usually leads to a programmed cell death. Glial cell infection causes their hyperreactivity, which can contribute to the development of COVID-19 associated neurodegeneration. Direct SARS-CoV-2 damage to neurons and glial cells requires the virus to be able to reach the nervous system, The two main routes od viral neuroinvasion are neuronal and hematogenous pathway. Besides a direct viral injury, neurological manifestations of COVID-19 can be caused by indirect mechanisms, including systemic inflammatory response, autoimmunity development and hypoxic brain injury. Listed mechanisms can lead to a wide spectrum of neurological manifestations of COVID-19. Neurological abnormalities can be mild and the only symptoms of the disease, or they can be a part of a severe form of the disease, when they are associated with considerably higher rates of mortality. Also, it is considered that SARS-CoV-2 infection could lead to long-term, neurodegenerative changes in some people. Considering COVID-19 is caused by a newly discovered coronavirus, the link between SARS-CoV-2 and the nervous system should be further investigated