After retrospectively analyzing the data of over 300,000 people, researchers in a recent Neurology journal paper report that a diagnosis of the coronavirus disease 2019 (COVID-19) was associated with a greater risk of both seizures and epilepsy as compared to those diagnosed with influenza infection.
Study: Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study. Image Credit: Chaikom / Shutterstock.com
Neurological symptoms of COVID-19
To date, COVID-19, caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has claimed over 6.6 million lives. In addition to its high mortality rate, COVID-19 is also associated with significant morbidity, particularly among patients who experience severe symptoms and are hospitalized due to this infection.
In fact, many people hospitalized due to COVID-19 report neurological symptoms, the most common of which include muscle aches, headaches, dizziness, confusion, and altered taste and smell. In some severe cases, COVID-19 has also been associated with seizures and strokes; however, these events are rare, with a seizure rate of about 1%.
How does COVID-19 affect the nervous system?
Although researchers previously thought that SARS-CoV-2 was capable of passing through the blood-brain barrier (BBB) to directly cause damage to the central nervous system (CNS), cerebrospinal fluid (CSF) samples of COVID-19 patients experiencing neurological symptoms have failed to exhibit the presence of viral genetic material.
A growing body of evidence suggests that immune activation and subsequent inflammation by the CNS is likely responsible for the neurological effects of COVID-19. More specifically, CSF samples obtained from acute COVID-19 patients were positive for interferon-regulated genes in dendritic cells, activated T-cells and natural killer (NK) cells, as well as increased levels of both interleukin-1 (IL-1) and IL-12 as compared to blood plasma levels.
Autopsy studies conducted on patients who have died from acute COVID-19 have also reported the accumulation of macrophages, CD8+ T-cells in perivascular regions, as well as widespread microglial activation. These findings suggest that despite the absence of SARS-CoV-2 within the CNS, the widespread inflammatory response and cytokine storm caused by COVID-19 likely upregulates the trafficking of these inflammatory molecules into the CNS.
Increased risk of seizures as compared to influenza patients
In the current study, the researchers analyzed the electronic records of over 300,000 patients, with both COVID-19 and influenza cohorts each consisting of 152,754 patients. Any patient with a history of epilepsy or recurrent seizures was not included in the study.
The six-month incidence of seizures or epilepsy was greater in the COVID-19 cohort as compared to the influenza cohort at 0.94% and 0.60%, respectively. When considered separately, the risk of seizures due to COVID-19 and influenza was 0.81% and 0.51%, respectively, whereas the risk of epilepsy was 0.30% and 0.17%, respectively.
When age was considered, COVID-19 was found to similarly increase the risk of seizures in both children and adults as compared to influenza infection. More specifically, children diagnosed with COVID-19 had a 1.34% risk of seizures or epilepsy as compared to a 0.69% risk when diagnosed with influenza. Conversely, adults had a 0.84% and 0.54% risk of seizures and epilepsy when diagnosed with COVID-19 or influenza, respectively.
Although patients hospitalized with COVID-19 are generally at an increased risk of neurological symptoms, the current study reported that non-hospitalized COVID-19 patients were more likely to experience seizures or epilepsy as compared to hospitalized patients.
The peak risk of seizures or epilepsy due to COVID-19 and influenza infection was about 23 days. In adults, this peak risk was 21 days, whereas the risk was greatest at 50 days following infection in children. In fact, at 50 days post-infection, children diagnosed with COVID-19 were three times more likely to experience seizures or epilepsy as compared to the same time point following influenza infection.
Despite the relaxation of most mask requirements and social distancing measures, SAR-CoV-2 continues to mutate and circulate throughout the world, thus indicating that COVID-19 remains a significant public health risk. The current study found that COVID-19 was associated with a greater risk of seizures as compared to influenza, with children particularly vulnerable to this neurological effect.
Further studies are needed to assess the long-term outcomes of COVID-19 patients who experience seizures.
- Taquet, M., Devinsky, O., Cross, H., et al. (2022). Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis: A Retrospective Cohort Study. Neurology. doi:10.1212/WNL.0000000000201595.