New SARS-CoV-2 BA.2.3.7 Sub-Variant With K97E Spike Mutation Is Causing Critical Neurological Illness In Children


An alarming report involving documented case studies and viral genome analysis by doctors, pediatrics and researchers from a  tertiary medical center in Taiwan ie the Tri-Service General Hospital which is part of the National Defense Medical Center has found that a newly emerged SARS-CoV-2 Omicron sub-variant of the BA.2.3.7 sub-lineage is causing critical neurological illness among children infected with that variant.

The medical researchers submitted their report to the peer reviewed International Journal of Infectious Diseases.

In Taiwan, another wave of the pandemic began in April 2022. Among the reported childhood cases, several patients presented with severe symptoms, including seizure, meningeal symptoms, and encephalopathy. These complications were also reported in Hong Kong (Tso et al., 2022) and Japan over previous Omicron epidemic.

However, studies in the reports lacked viral genome sequencing data. Therefore, we investigated the pediatric patients with similar complications admitted to our hospital during the outbreak, and we attempted to elucidate commonalities between them.


Based on our patients’ findings, the increased cytokine and inflammation markers while having negative PCR results in CSF, can lead to the conclusion of the causes of these severe neurological symptoms might be related to hyperimmune states rather than direct viral invasion of CNS.

Our analysis of the eight TSGH sequences indicated that a new Omicron BA.2.3.7 subspecies with special S protein K97E may have been produced in Taiwan and these sequences are similar from Japan, USA, and Hong Kong.

The location of K97 is between two beta sheets and the edge of the druggable cavity region of S protein NTD domain (Di Gaetano et al., 2021) and some extensive ubiquitination events have been observed on them (Stukalov et al., 2021) which might have effect on immune regulation. Furthermore, mutations of the NTD region in S protein that allow for immune evasion have also been reported (Harvey et al., 2021).

Therefore, the K97E mutation, which has not been observed in Taiwan previously, potentially explains the sudden increase in incidence of severe neurological symptoms in pediatric patients due to its possible effect on immune regulation.



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