Case Study of Child with Neurologic Symptoms Associated with COVID-19

It has been commonly thought  that children infected with SARS-CoV-2 rarely develop severe symptoms compared to adults. Although there have been a number of  cases of Kawasaki-like disease associated with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), it is rare for kids to develop neurological post-COVID complications as part of MIS-C. Recently, a case report published in Neurology describes a two-year-old who developed multisystem inflammatory syndrome in children (MIS-C) with associated neurological complications (Abel et al., 2020). Of note, MIS-C presents in a similar manner to Kawasaki disease, which includes symptoms such as “persistent fever, elevated inflammatory markers, and multisystem organ involvement.” 

A 33-month-old boy presented to the hospital with a 2 day history of “fever, emesis, and rash”. He was tachycardic (high heart rate) and had erythematous macules (flat, red rash) on his thighs. Initial nasopharyngeal swab was negative for SARS-CoV-2 but a repeat was inconclusive. Antibody testing for SARS-CoV-2 was positive. Blood work revealed normal white blood cell count except for bandemia (excess of immature white blood cells in the blood) and elevated inflammatory markers (C-reactive protein and ferritin). Chest scan and cardiac markers were normal, but echocardiogram revealed trace pericardial effusion (small amounts of fluid around the heart). The report includes a detailed figure of the patient’s clinical course.

Over the following 24 hours, the patient’s respiratory function deteriorated and he required noninvasive respiratory support but was still alert and active. A second chest scan revealed bilateral pleural effusions (buildup of fluid between membranes lining the lungs). A second echocardiogram revealed reduced left ventricular systolic function. Blood work revealed increasing inflammatory and cardiac markers and thrombocytopenia (low platelet count). By day 6, the patient “became increasingly somnolent in the absence of sedative medications.” Neurology consultants detailed  that the “patient was somnolent, with slight facial grimace to noxious stimuli, diffuse hypotonia (decreased muscle tone), and significant weakness.” Noncontrast head CT scan and lumbar puncture were unremarkable. CSF PCR was negative for SARS-CoV-2. Metabolic workup was normal except for hyperammonemia (high levels of ammonia in the blood). “EEG showed moderate background slowing.” The following day the patient showed slight improvement, including eye opening and reaction to noxious stimuli.  Brain MRI revealed “restricted diffusion in the bilateral thalamic nuclei without T2/fluid-attenuated inversion recovery changes.”

By day 9, the patient’s neurologic status improved, and he was able to “consistently follow commands, communicate verbally, and regained his motor function, although he remained weak.” He was walking by day 12. A follow-up EEG on day 12 revealed mild diffuse slowing and an MRI on day 15 revealed resolution of the bilateral thalamic lesions. He was discharged on day 15. The authors note that EEGs from adults with COVID-19 have also revealed “slowing with a disorganized background” but with the caveat that most adults were receiving sedatives or antiseizure medications, whereas the child in this case did not. Because this patient’s encephalopathy coincided with his marked systemic inflammatory response, the authors believe  that this case of MIS-C was due to post-infectious or inflammatory CNS effect and likely not a result of direct viral entry into the CNS since the SARS-CoV-2  PCR was negative in the CSF.

This case report supports the findings of other case reports that the primary etiology of neurologic symptoms either during or post-COVID-19 infection is secondary to severe immune activation rather than due to direct viral entry into the CNS. Consolidating this trend with the evidence that SARS-CoV-2 has neuroinvasive potential and has been detected in post-mortem brain tissue will be an important step in creating a more comprehensive picture of how SARS-CoV-2 impacts the brain.