Basic Mechanisms: How Respiratory Viruses Can Affect the Brain

People walking in the city with face masks to prevent respiratory viruses

Epilepsy News From:

Tuesday, January 19, 2021

While COVID-19 infection is affecting individuals worldwide, it is important to remember that there is no clinical evidence that COVID-19 infection worsens seizures in people with epilepsy.1 However, there is value in understanding the impact of respiratory viruses (such as COVID-19) in epilepsy, the potential mechanisms of neuronal infection, and the consequences of inflammation in the brain.

  • SARS-CoV-2, the virus that causes the disease COVID-19, presents itself as an upper respiratory tract infection in most patients with symptoms ranging from fever, cough, shortness of breath, congestion, headache, nausea, fatigue, and/or a loss of sense of smell and/or taste.
  • There are very few reports of COVID-19 causing generalized/focal seizures or presenting as very prolonged seizures (status epilepticus) as the initial symptom. It is important to note that:
    • Many weren’t followed up after the acute phase.
    • Most patients recovered with drugs known to be anti-seizure treatments.
    • The studies regarding presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of patients have been inconclusive.
    • Given this data and the relatively rare occurrence of new-onset seizures, it is possible (even likely) that such occurrences were a coincidence.

In general, fever and viral infection can potentially affect the severity and frequency of seizures. However, there is limited scientific data on what neurological symptoms can result from infection with SARS-CoV-2.

How might SARS-CoV-2 affect the brain?

Following is a list of hypothetical mechanisms of how SARS-CoV-2 might affect the brain directly or indirectly:

  • Coronaviruses including SARS-CoV-2 are documented to have a neuroinvasive capacity, which means that they can access the central nervous system (CNS) through the bloodstream by infecting specific cells, or they might infect immune cells that then travel to the CNS. Indirectly, the virus might enter the CNS through the olfactory nerve present in the nose which could explain the partial loss of sense of smell/taste or through the vagus nerve which interfaces with multiple different organs.
  • SARS-CoV-2 binds to a protein called angiotensin‐converting enzyme 2 (ACE2) to enter and invade host cells. ACE2 is present on many different types of human cells including specific cells in the lung, nose, and the brain. ACE2 is important for protecting the cells against stress and inflammation. Angiotensin and ACE2 have been shown to be involved in certain epilepsies.2,3 One potential mechanism of SARS-CoV-2 could be through its effect on the angiotensin system.
  • SARS-CoV-2 induces a phenomenon called “cytokine storm” in some patients. Cytokines are small proteins produced by specific immune cells that signal certain changes in the body to defend against the invading virus or bacteria that can cause disease. An excessive production of inflammatory cytokines such as those triggered by SARS-CoV-2, however, can be devastating to multiple organs. Cytokines have been implicated in febrile seizures in patients with epilepsy.Inflammation including fever can cause elevated levels of some cytokines, leading to increased seizures. Cytokines can cross the blood brain barrier which typically protects the brain from toxins and pathogens in the bloodstream and cause injury to brain cells in patients with severe COVID-19. However, there are no scientific reports thus far supporting the role of cytokines in COVID-19.
  • In patients with severe COVID-19, infection as well as lung involvement leading to low oxygen levels (hypoxia) might cause the blood brain barrier to become “leaky,” leading to complications such as worsened seizures, brain inflammation (encephalitis), and/or stroke.

The above reflects the various methods respiratory pathogens such as SARS-CoV-2 could use to invade the brain. The immune system generates an appropriate response to counter the virus and, in most cases, these are enough to protect the patient.

In some cases, the severity of the viral infection along with increased inflammatory reactions and increased risk factors leads to severe events such as severe brain inflammation and long-term damage to brain cells. While clinical studies will be important to understand the specifics and extent of SARS-CoV-2 infection in epilepsy and the use of anti-inflammatory drugs, basic science studies will reveal the exact mechanism of SARS-CoV-2 infection and its effect on the brain.

References

  1. Vohora D,Jain S, Tripathi M, Potschka H. COVID‐19 and seizures: Is there a link? Epilepsia. 2020 Sep 17: 10.1111/epi.16656.
  2. Argañaraz GA, Konno AC, Perosa SR, et al. The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis. Epilepsia. 2008 Aug;49(8):1348-57.
  3. Pereira MG, Becari C, Oliveira JAC, et al., Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy. Clin Sci (Lond). 2010 Aug 17;119(11):477-82.
  4. Chen Q, Li M, Zhang X, et al. Association between interleukin-6 gene polymorphisms and febrile seizure risk. Medicine (Baltimore). 2019 Sep; 98(39): e17167.
Authored by: Ramya Lakshminarayan PhD on 1/2021
Reviewed by: Sloka Iyengar PhD | PMP on 1/2021

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