key: cord-0928730-s3wo3ten
authors: Roe, Kevin
title: Explanation for COVID‐19 infection neurological damage and reactivations
date: 2020-05-04
journal: Transbound Emerg Dis
DOI: 10.1111/tbed.13594
sha: db3614fa2143fb5dc127b32198b4393034e8b496
doc_id: 928730
cord_uid: s3wo3ten

A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests, were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral hemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment, and nerve pain; and skeletal muscle injury (Mao, 2020).

nificant mortality (Mao et al., 2020) . From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral haemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment and nerve pain; and skeletal muscle injury (Mao et al., 2020) .

The reactivation of previous COVID-19 infections after recent previously negative test results has also been reported in about 9% of a small study of patients (55 total patients with five reactivations, but the time window of reactivation observation was only 17 days long, and more reactivations could likely have been seen over a longer time period), and this and other disturbing reports of COVID-19 reactivation will likely be unwelcome and met with skepticism (Ye et al., 2020) . The patients, aged 27-42 years old, who had reactivation of COVID-19 did not have any underlying diseases, such as diabetes, chronic hypertension or cardiovascular disease; and reactivations occurred regardless of any anti-viral therapy received, without any discovery of any clinical characteristics to enable the prediction of future viral reactivation (Ye et al., 2020) . COVID-19 has also shown about 80% genetic similarity to the severe acute respiratory symptom (SARS) virus, which is already known to be derived from a bat virus (Ye et al., 2020) . (Wong et al., 2002) . Nipah virus is another untreatable and lethal virus, transmissible by bodily secretions of humans and other mammals, and even considered fully capable of a world-wide pandemic spread after mutation (CDC, 2014; Luby, 2013; Thibault et al., 2017; WHO, 2018; World Health Organization, 2018) .

The COVID-19 virus and Nipah virus illustrate the virulence of some viral pathogens after transmission from animals to humans. Some viral pathogens can display a high replication rate in host cells after transmission to secondary hosts of other species, such as in the case of viruses that originally evolved high replication rates while they infected animals such as bats and thereby were selected by the fast immune responses of bats (Brook et al., 2020) . This is characteristic of several enveloped RNA viruses, including Nipah virus of the genus Henipavirus and severe acute respiratory syndrome (SARS) virus of the genus Betacoronavirus (Brook et al., 2020; Flint, Racanielllo, Rall, Skalka, & Enquist, 2015) .

There is a very good reason for viruses, such as COVID-19 and Nipah virus, to selectively infect neurons, because this enables them to evade attacks from the immune system of the host. Almost all T-cell activations require that an antigen (i.e., a molecular pattern that a patient's immune system recognizes as foreign to the patient) be presented by another cell, such as a dendritic cell, on a specific surface protein known as a major histocompatibility complex (MHC) (Alberts et al., 2015) . In humans, this is also called a human-leukocyte-associated (HLA) protein (Alberts et al., 2015) . T cells predominantly are α:β T cells with the MHC requirement for antigen presentation to activate α:β T cells, such as MHC class II for presentation to CD4 T cells and MHC class I for presentation to cytotoxic CD8 T cells (Alberts et al., 2015) . But neurons carry very few of these MHC proteins, so they cannot easily present viruses on MHC class I to cytotoxic CD8 T cells to induce an attack on the infected neurons (Murphy, 2012). Therefore, several viruses, such as the herpesviruses including the herpes simplex virus and the herpes zoster virus, also evade the

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