COVID-19 and olfactory dysfunction: A possible associative approach towards neurodegenerative diseases

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of novel coronavirus 2019 (COVID-19), has kept the globe in disquiets due to its severe life-threatening conditions. The most common symptoms of COVID-19 are fever, sore throat, and shortness of breath. According to the anecdotal reports from the health care workers, it has been suggested that the virus could reach the brain and can cause anosmia, hyposmia, hypogeusia, and hypopsia. Once the SARS-CoV-2 has entered the central nervous system (CNS), it can either exit in an inactive form in the tissues or may lead to neuroinflammation. Here, we aim to discuss the chronic infection of the olfactory bulb region of the brain by SARS-CoV-2 and how this could affect the nearby residing neurons in the host. We further review the probable cellular mechanism and activation of the microglia 1 phenotype possibly leading to various neurodegenerative disorders. In conclusion, SARS-CoV-2 might probably infect the olfactory bulb neuron enervating the nasal epithelium accessing the CNS and might cause neurodegenerative diseases in the future.

Keywords: COVID-19; SARS-CoV-2 neuroinvasion; neurodegenerative disorders; neuroinflammation; olfactory bulb dysfunction.

Figure 1

Mechanism of action for COVID‐19 neuroinvasion. Figure 1 depicts the hypothetical mechanism of entry of SARS‐CoV‐2 inside the CNS via olfactory bulb along with the mechanism involved in olfactory bulb dysfunction. This image is evident that both the pathways of mechanism are similar where the M1 phenotype of microglia gets activated which may further stimulate the pro‐inflammatory cytokines that have the possibility of resulting in neuroinflammation. COVID‐19, coronavirus 2019; CNS, central nervous system; M1, microglia 1; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 2

Depiction of the possible role of SARS‐CoV‐2 to cause neurodegenerative diseases. The entry of SARS‐CoV‐2 in the CNS through olfactory bulb upon nasal infection may possibly cause inflammation and demyelination. Upon binding with the olfactory bulb, the viral replication is initiated. ORF3a, ORF8b, E proteins, and the NF‐KB pathway activate the inflammasome pathway through various means, leading to the activation of cytokine. This results in a cytokine storm, which further results into various neuronal inflammations and may result into neurodegenerative disorders. CNS, central nervous system; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2