Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020

Abstract

There are few detailed investigations of neurologic complications in severe acute respiratory syndrome coronavirus 2 infection. We describe 3 patients with laboratory-confirmed coronavirus disease who had encephalopathy and encephalitis develop. Neuroimaging showed nonenhancing unilateral, bilateral, and midline changes not readily attributable to vascular causes. All 3 patients had increased cerebrospinal fluid (CSF) levels of anti-S1 IgM. One patient who died also had increased levels of anti-envelope protein IgM. CSF analysis also showed markedly increased levels of interleukin (IL)-6, IL-8, and IL-10, but severe acute respiratory syndrome coronavirus 2 was not identified in any CSF sample. These changes provide evidence of CSF periinfectious/postinfectious inflammatory changes during coronavirus disease with neurologic complications.

Keywords: Atlanta; COVID-19; CSF; Georgia; SARS-CoV-2; United States; cerebrospinal fluid; coronavirus disease; coronaviruses; cytokines; encephalitis; encephalopathy; meningitis/encephalitis; respiratory infections; serologic analysis; severe acute respiratory syndrome coronavirus 2; viruses; zoonoses.

Figure 1

Magnetic resonance imaging findings for 3 patients with coronavirus disease who had neurologic complications, Atlanta, Georgia, USA, 2020. A–D) Patient 1 had right cerebral hemispheric restricted diffusion (diffusion weighted imaging in panel A) and cerebral edema (fluid-attenuated inversion recovery [FLAIR] in panel B) affecting gray matter and deep gray nuclei, without enhancement (panel C), and spinal edema (panel D). E, F) Patient 2 had a splenium lesion (diffusion weighted imaging in panel E and FLAIR recovery in panel F that was nonenhancing). Arrows indicate lesions in the splenium. G) Patient 3 had an equivocal fluid-attenuated inversion recovery FLAIR abnormality in the right temporal lobe.

Figure 2

Cerebrospinal fluid (A and B) and inflammatory protein (C) analyses for patients with coronavirus disease and neurologic complications, Atlanta, Georgia, USA, 2020. Compared with healthy controls and patients who had HIV-associated neurocognitive disorder, CSF levels of anti-S1 IgM were high in patient 1, and moderately high in patients 2 and 3. In contrast, levels of CSF anti-E IgM were high only for patient 1 and within references ranges for patients 2 and 3. CSF inflammatory analysis showed increased levels of IL-8 and IL-10 more unique to neuro-COVID, and increased levels of IP-10 and TNF-α in neuro-COVID and HIV-neuro. Circles indicate patients whose interleukin levels were tested and used as controls (healthy, HIV). Horizontal bars indicate average values. COVID-neuro, coronavirus disease–associated neurologic complications; HIV-neuro, HIV-associated neurocognitive disorder; IL, interleukin; IP, interferon-γ–induced protein; OD, optical density, ND, not determined; neuro-COVID, neurologic complications associated with coronavirus disease; TNF, tumor necrosis factor.