Critical pediatric neurological illness associated with COVID-19 (Omicron BA.2.3.7 variant) infection in Taiwan: immunological assessment and viral genome analysis in tertiary medical center

Abstract

Objectives: Since April 2022, another wave of the Omicron epidemic has struck Taiwanese society, and children with severe neurological complications have been reported frequently. A few cases even developed acute fulminant encephalitis. To investigate the possible causes of the increased incidence of such complications in Taiwan, we reviewed several cases of pediatric patients with severe neurological symptoms.

Methods: We collected the medical records of pediatric patients with COVID-19 infection who presented with severe neurological symptoms. The COVID-19 infection was diagnosed by nasal swab reverse transcriptase-polymerase chain reaction. The remaining samples were sent for whole genome sequencing and spike (S) protein amino acid variation mapping.

Results: The increase of several inflammatory markers was observed in all patients included in this study. However, none of the cerebrospinal fluid samples tested positive for SARS-CoV-2. The result of whole genome sequencing showed that all the sequences belonged to the lineage BA.2.3.7. However, the sequences had a K97E mutation in the S protein that differed from other BA.2.3.7 lineage strains, which was located at the S protein N-terminal domain.

Conclusion: The new mutation in the S protein, which had not previously been observed but was discovered in this study, potentially explains the sudden increase in incidence of extremely adverse neurological symptoms in pediatric patients.

Keywords: Amino acid variation; COVID-19; Pediatric cases; Severe neurological symptoms; Spike protein; Whole genome sequencing.