Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients

Abstract

Respiratory viruses are opportunistic pathogens that infect the upper respiratory tract in humans and cause severe illnesses, especially in vulnerable populations. Some viruses have neuroinvasive properties and activate the immune response in the brain. These immune events may be neuroprotective or they may cause long-term damage similar to what is seen in some neurodegenerative diseases. The new "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) is one of the Respiratory viruses causing highly acute lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical similarities to those reported in "Severe Acute Respiratory Syndrome Coronavirus"(SARS-CoV) and the "Middle East Respiratory Syndrome Coronavirus"(MERS-CoV) including neurological manifestation. To examine the possible neurological damage induced by SARS-CoV-2, it is necessary to understand the immune reactions to viral infection in the brain, and their short- and long-term consequences. Considering the similarities between SARS-CoV and SARS-CoV-2, which will be discussed, cooperative homological and phylogenetical studies lead us to question if SARS-CoV-2 can have similar neuroinvasive capacities and neuroinflammatiory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. To explain the neurological manifestation caused by SARS-CoV-2, we will present a literature review of 765 COVID-19 patients, in which 18% had neurological symptoms and complications, including encephalopathy, encephalitis and cerebrovascular pathologies, acute myelitis, and Guillain-Barré syndrome. Clinical studies describe anosmia or partial loss of the sense of smell as the most frequent symptom in COVID19 patients, suggesting that olfactory dysfunction and the initial ultrarapid immune responses could be a prognostic factor.

Keywords: Acute and chronic neurological diseases; CNS infection; COVID-19; Encephalitis; Encephalopathy; Human coronavirus; Human respiratory virus; Neuroinvasion; Respiratory viral infection.

Fig. 1

Immune control of viral infections

Fig. 2

Several viruses spread to the CNS by infecting the neuron receptor in the nasal olfactory epithelium to reach the brain by axonal transport along the olfactory nerve

Fig. 3

Some respiratory viruses spread from the lungs to the CNS through the vagus nerve

Fig. 4

a Several viruses spread to the CNS by infecting the neuron receptor in the nasal olfactory epithelium to reach the brain by axonal transport along the olfactory nerve. b Some respiratory viruses spread from the lungs to the CNS through the vagus nerve