Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Abstract

Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

Nervous system involvement after infection with COVID-19 and other coronaviruses

“…The secondary release into the blood may increase the permeability of the blood-brain barrier through the produced cytokines, thereby promoting the virus to enter the brain and causing viral encephalitis (Unni et al, 2011). Although there is rare evidence that CoV, especially SARS-CoV-2, invade the nervous system via the blood circulation pathway (Koyuncu et al, 2013;Desforges et al, 2019), subsequent studies are expected.…”

“…The unique anatomical organization of olfactory nerves and the olfactory bulb in the nasal cavity and forebrain effectively makes it a channel between the nasal epithelium and the CNS (Koyuncu et al, 2013). As a consequence, CoV can enter the brain through the olfactory tract in the early stages of infection or nasal vaccination (Desforges et al, 2019;Mori, 2015). For example, after CoV infects nasal cells, it can reach the entire brain and cerebrospinal fluid through the olfactory nerve and olfactory bulb within 7 days and cause inflammation and demyelinating reaction.…”

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

“…While features of Parkinsonism and Parkinson's disease (PD) have not been described in association with CoV pandemics or outbreaks, anti-CoV antibodies have been identified in cerebrospinal fluid (CSF) of individuals with Parkinson's disease (Fazzini et al, 1992). Given that neural and immune cells can serve as reservoirs of latent CoV, it is plausible that this could contribute to delayed neurodegenerative processes (Desforges et al, 2019), but this also, remains to be seen in COVID-…”

“…The neuroinvasive potential of CoV has been reported in SARS-CoV-1 patients and experimental animals, and spread from the respiratory tract to the CNS could occur via retrograde axonal transport from peripheral nerves such as the olfactory nerve, or via hematogenous spread (Desforges et al, 2019). After entering the CNS, CoV has been shown to induce neuronal cell death in mice (Netland et al, 2008).…”

Ensuring mental health care during the SARS-CoV-2 epidemic in France: A narrative review

“… The possibility of specific clinical forms: While several respiratory virus infections, including SARS-CoV-1, can produce neurological profiles (encephalitis, seizures), there is no data for SARS-CoV-2 (20,21). There has been a recent epidemiological alert concerning anosmia and ageusia without nasal congestion which could be linked to neurological damage (22).…”