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. 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.

Evidence of central nervous system infection and neuroinvasive routes, as well as neurological involvement, in the lethality of SARS‐CoV‐2 infection

“…Up to September 14, 2020, a total of 20 autopsy studies on neuropathology were retrieved, among which CNS detection of SARS‐CoV‐2 was negative in 12 (of 12) cases from three studies, 36,42,43 and positive in 58 (of 87) cases (66.7%) from nine studies, 46‐54 and unavailable for 109 cases in eight studies 35,37‐41,44,45 …”

“…On September 9, Freij et al 54 reported a 5‐year‐old girl who died from CNS co‐infection with SARS‐CoV‐2 and tuberculosis. Tests for SARS‐CoV‐2 RNA were negative in CSF, but positive in the biopsy tissue from the cerebellum.…”

“…Several postmortem studies showed that despite the presence of SARS‐CoV‐2 in the brain parenchyma of some patients, RT‐PCR tests for SARS‐CoV‐2 were negative in their CSF 49,54 . This indicates that negative outcomes of PCR tests in CSF do not mean the absence of SARS‐CoV‐2 in the CNS.…”

Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease

“…Autopsy reports to date have described meningitis and/or encephalitis in small numbers of patients dying with COVID-19 disease 37–45 , and more frequently, both ischemic and/or hemorrhagic acute or subacute cerebrovascular lesions 37,39,44,46–57 , but these have not always been supported by direct evidence of CNS SCV2 presence. Elements of the classical neuropathology of viral CNS infections 58,59 , including lymphocytic leptomeningitis and encephalitis, microglial nodules, perivascular lymphocytic cuffing, focal demyelination and viral inclusions, have most often been absent.…”

“…Elements of the classical neuropathology of viral CNS infections 58,59 , including lymphocytic leptomeningitis and encephalitis, microglial nodules, perivascular lymphocytic cuffing, focal demyelination and viral inclusions, have most often been absent. There have been at least 16 published studies 36,38,39,45,47–50,60–67 that used gold-standard RT-PCR methods to interrogate SCV2 genomic presence in postmortem brain tissue, but each of these have examined relatively few brain regions. The brain has hundreds of anatomically-distinct regions with possibly thousands of different cell phenotypes.…”