Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child

Abstract

Background: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens.

Case presentation: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread.

Conclusion: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Keywords: CNS tuberculosis; Case report; Meningoencephalitis; Pediatric infections; SARS-CoV-2.

Fig. 1

Selected sequential MRI/MRA images. a Diffusion-weighted image shows a 7 mm area of restriction diffusion in the left anterior frontal lobe subcortical white matter (arrow), day 12 of illness; b T1-weighted image with gadolinium showing mild leptomeningeal enhancement along the tentorium, day 12; c Diffusion-weighted image showing no restriction diffusion in the left anterior frontal lobe subcortical white matter, day 16; d T2 FLAIR shows abnormal increased signal mainly involving the midbrain, bilateral deep frontal, and bilateral medial temporal areas, day 16; e 3-D time of flight MRA shows a normal circle of Willis, day 16; f T1-weighted image with gadolinium showing diffuse leptomeningeal enhancement, day 16; g T2 FLAIR showing extensive grey matter lesions involving the deep frontal lobe, temporal lobe, midbrain, and cerebellar vermis, with no obvious cerebellar involvement, day 30; h 3-D time of flight MRA showing no flow in intracranial vessels with flow in extracranial vessels, day 30

Fig. 2

Evolution of SARS-CoV-2 IgA and IgG responses by enzyme immunoassay (EUROIMMUN AG, Germany). OD = Optical density

Fig. 3

Cerebellar biopsy histopathology. a High power view of a necrotizing granuloma showing central pale eosinophilic caseous-type necrosis; b High power view revealing numerous acid-fast bacilli within the granuloma; c Low power view of medium-sized blood vessel with numerous inflammatory cells and severe damage to the vessel wall with essentially complete loss of internal elastic lamina (vasculitis); d High power view revealing numerous acid-fast bacilli identified in same vessel wall. Hematoxylin-Eosin stained sections (a, c); Fite stain (b, d)