The Causes and Long-Term Consequences of Viral Encephalitis

Abstract

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

Neurotrophin Signaling Impairment by Viral Infections in the Central Nervous System

“…Regarding hRSV and SARS-CoV-2, learning and memory impairment cause cognitive problems that have been previously described [ 149 ]. In this line, it could be suggested that, as previously mentioned in the case of the influenza virus [ 142 , 154 ], the learning and memory impairment could be associated with an alteration in the levels of BDNF. Interestingly, after the infection with SARS-CoV-2, the patients that developed symptoms such as depression and anxiety presented lower levels of BDNF compared to the controls [ 160 ].…”

“…Neurotropic viruses can interfere with the correct signaling pathway of NTs and cause neurological pathologies. However, these pathologies can persist in the long term, causing disorders such as learning and memory impairment, mood and speech disorders, and degenerative diseases [ 154 ].…”

“…Even though no specific studies associate the interference of the NTs signaling due to the infection with respiratory viruses can cause a long-term sequel, it is possible to suggest an association. For example, the influenza virus is one of the respiratory viruses known for causing long-term consequences, such as learning and memory impairment [ 154 ]. It has been demonstrated that infection with the influenza virus could decrease the levels of BDNF and NGF in the hippocampal region [ 142 ].…”

“…It has been demonstrated that infection with the influenza virus could decrease the levels of BDNF and NGF in the hippocampal region [ 142 ]. This may contribute to the long-term effects of influenza in the brain, such as cognitive impairment [ 142 , 154 ].…”

“Don’t Look Up” Your Science—Herd Immunity or Herd Mentality?

“…We have been fighting influenza for decades. Influenza induces short- and long-term symptoms and kills people in a similar way to COVID, and the same target population is at risk [ 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. We have a standard of care in place with influenza symptoms and other respiratory diseases, some of which could have been better used to treat COVID.…”