Letter to the editor response

We thank Finsterer et al for offering their insights and interest in our retrospective study, where we identified 44 pediatric subjects who had a diagnostic code of “simple febrile convulsions” (30 [68.2%]) or “complex febrile convulsions” (14 [31.8%]) and an associated COVID-19 diagnostic code. We understand their concerns, and will attempt to address them below.

We thank Finsterer et al for highlighting in our article that coinfections were observed in COVID-19 pediatric patients who were reported to have a febrile seizure. Because of database limitations, particularly not having access to clinical documentation, we were unable to determine if COVID-19 or an alternate infectious etiology was the most likely cause for the seizure. We opted to include that datum and list it as a limitation in the manuscript, because it also cannot be excluded that SARS-CoV-2 was responsible.

We agree with Finsterer et al that a systematic approach to the evaluation of the cause of febrile seizures should be completed, for example, excluding serious bacterial infections in children who appear unwell. ¹ As stated, this was a retrospective study using electronic health record data elements (available diagnostic and procedure codes) that are retrieved from multiple centers throughout the United States. The data we evaluate, therefore, is limited by code entry in the electronic health record by the clinician as he or she is managing these patients. Thus, when a diagnostic code of “simple febrile convulsions” is present, the patient was likely diagnosed with a simple febrile seizure at the time of entry. We do acknowledge that because we did not have all the clinical data (including documentation of a family history, presence of fever, etc.), we could not confirm if the diagnoses entered were correct. Although the advantage of utilizing a large database as we did has its obvious advantages, the limitations as described can lead to some unanswered questions.

In our study, not all subjects required antiseizure medication. Based on the data we were able to retrieve, we were unable to determine why 28 patients did not require antiseizure medication. In a majority of patients with simple febrile seizures (which also comprised a majority of our cohort), intervention to halt a seizure is usually unnecessary as it resolves spontaneously. ² It is possible, in those subjects who received therapy, febrile status epilepticus was present (which rarely stops spontaneously), requiring aggressive treatment. ³

Currently, the pathogenesis of neuro-COVID is not completely understood. We do agree with Finsterer et al that the type of injury may vary depending on the severity of COVID-19 infection. This can include direct viral invasion of neural cells, possible viral invasion of endothelial cells versus neural cells resulting in vascular endothelial injury, and immune-mediated disorders. ⁴ Our understanding is expected to evolve as we learn more about COVID-19 and its associated neurologic complications in children.

COVID-19–associated febrile seizures may be an uncommon occurrence. We look forward to additional studies to help evaluate the incidence of febrile seizures in children with SARS-CoV-2 and overcome the limitations inherent in our large deidentified database study.