Exclude differentials before diagnosing SARS-CoV-2-associated acute haemorrhagic necrotising encephalitis.

Letter to the Editor

We eagerly read the article by Mierzewska-Schmidt et al., about a 2-month-old boy who developed progressive neurological compromise (initially irritability, apathia, nystagmus) 2 days after the clinical onset of COVID-19 (Mierzewska-Schmidt et al., 2021). On cerebrospinal fluid (CSF) investigation pleocytosis, lactic acidosis, and low glucose was noted, and cerebral magnetic resonance imaging (MRI) helped diagnose acute, hemorrhaghic, necrotising encephalitis (AHNE) (Mierzewska-Schmidt et al., 2021). Despite maximal treatment, the patient died shortly after admission to the paediatric intensive care unit (Mierzewska-Schmidt et al., 2021). The study is interesting but raises concerns that need to be addressed.

We do not agree with the notion that SARS-CoV-2-associated AHNE has not been reported previously in the paediatric population (Mierzewska-Schmidt et al., 2021). In a 9-month-old boy, acute necrotising encephalopathy (ANE) has been described that later progressed to AHNE (Lazarte-Rantes et al., 2021).

We do not agree with the notion that “paediatric COVID-19 is commonly benign” (Mierzewska-Schmidt et al., 2021). Paediatric patients with COVID-19 may develop multisystem inflammatory syndrome in children (MIS-C), severe dengue with multi-inflammatory syndrome, fatal ventricular arrhythmias, autoimmune encephalitis, fatal cerebral vasculitis, chorea, and several other severe complications.

We should be told which tests the “CSF meningoencephalitis PCR panel” included. Particularly, we should know if the CSF was investigated for Mycobacterium tuberculosis. Exclusion of tuberculosis is crucial as AHNE has been previously reported in association with cerebral tuberculosis (Ermilov et al., 2021). Arguments for tuberculous meningitis in the index patient are the mild pleocytosis, low CSF glucose, and lactic acidosis.

A limitation of the study is that only a single CSF result was provided. In the case of an unproven diagnosis with pleocytosis, it is crucial to track the abnormal CSF parameters over time.

The confirmation of SARS-CoV-2 in the CSF is absent. To establish a causal relation between COVID-19 and AHNE it is essential that the presence of the virus in the CSF is documented. It is also warranted that the CSF had been investigated for cytokines, chemokines, and glial markers, as they have been reported to be elevated in immunological central nervous system (CNS) disease following a SARS-CoV-2 infection (Gigli et al., 2020).

The results of the autopsy are also absent, particularly the results of neuropathological and microbial investigations of the brain tissue and the CSF. Of particular interest is if SARS-CoV-2 could be detected within neurons or glial cells as it has been previously reported in patients with encephalitis (Porzionato et al., 2021).

Overall, this interesting study has some limitations that challenge the results and their interpretation. Cerebral tuberculosis should have been excluded and an autopsy study should have been performed.

Author contribution

DM: literature search, discussion, critical comments, final approval, JF: design, literature search, discussion, first draft, critical comments.

Declaration of Competing Interest

There are no conflicts of interest.