2. SARS-CoV-2 direct effect on central nervous system
Several hypotheses try to describe the reason for the neurological symptoms. Some works describe a direct result of the local invasion of the central nervous system (CNS) by SARS-CoV-2. SARS-CoV-2 infection has been linked to increased neuroinflammation in Alzheimer diseases patients [14]. Similar to describe for other neurotropic viruses, coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, and MERS-CoV) that are able to trigger neurotoxicity, causing nervous system damage through demyelination, inflammatory state and hypoxia injury [15]. The ability of SARS-CoV-2 to reproduce in the olfactory mucosa has been demonstrated in both human and animal models [16,17], indicating that the olfactory nerve may serve as a crucial entry point into the CNS [5,18-20], as has previously been seen for other respiratory viruses [21]. In two-thirds of hospitalized patients, nerve terminals like the olfactory or auditory nerves exhibit abnormalities in the central nervous system or destruction [11]. SARS-CoV-2 viral RNA, or virus antigen, might be found in the CNS [22,23]. Althought, COVID-19 individuals with neurological symptoms have only infrequently had SARS-CoV-2 viral RNA found in their cerebrospinal fluid [24-26], brain tissues from postmortem victims have been shown to have the SARS-CoV-2 antigen and virus RNA [27]. Additionally, COVID-19 seems to trigger or, at least, accelerate neurological disorders in people infected by SARS-CoV-2 [28].