key: cord-0691743-1enb5qcu
authors: De Santis, Giuseppe
title: SARS-CoV-2: a new virus but a familiar inflammation brain pattern
date: 2020-04-27
journal: Brain Behav Immun
DOI: 10.1016/j.bbi.2020.04.066
sha: a983425c5dd0abfb8c6ca82a545fa49bdb36fc73
doc_id: 691743
cord_uid: 1enb5qcu

nan

Dear Editor, two recent articles (Wu et al, 2020; Ye et al, 2020) Il-1beta and Il-6 were measured to be increased in the spinal cord of infected mice. Butler et al (2006) showed that in mice infected intranasally with neurovirulent strains of HCoV-OC43, virus enters the CNS via the olfactory nerves with subsequent transneuronal retrograde dissemination to distant connections of the olfactory bulb and primarly infects pyriform cortex and brainstem.

Along with previous findings on Coronavirus, it is reasonable to think that SARS-CoV-2 enters the CNS via the olfactory bulb and may reach brainstem causing disfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Along with previous investigations, Coronavirus infection of human CNS seems to be restricted to neurons and the lack of inflammation in infected brains raises the possibility that neurons die by apoptosis, a form of cell death associated with minimal cellular infiltration. Whether this occurs in infected subjects and interferes with initiation of the immune response is not known at present but it may be one mechanism that would result in a diminished inflammatory response.

Furthermore neurons do not normally express MHC class I or II antigen and express only low levels of the machinery required for loading peptide onto MHC class I antigen. However, neuronal production of IL-6 in vivo following viral infection has been previously reported (Netland et al, 2008) . It is also possible that excessive levels of proinflammatory cytokines/chemokines in the brain result in a "cytokine storm" and lethal disease. It is well established that excessive production of cytokines can lead to harmful effects in the brain and other tissues. An excessive and possibly dysregulated cytokine response has been implicated in neuronal death and death of the animal in an experimental model of Japanese encephalitis virus infection and it has also been implicated in patients with SARS. Lending support to this hypothesis, three cytokines are often associated with inflammation in SARS-Cov-2 patients: IL-1, tumor necrosis factor alpha, and IL-6.

Together, these data suggest that anosmia (about half of patients with COVID-19 present with anosmia) can be an early indicator of CNS involvement in course of physicians should be aware about more probable worsening of clinical conditions, especially do to the fact that SARS-CoV-2 can itself causes an important respiratory insufficiency, together with the possible depression of cardiorespiratory centers.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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