Clinical features of SARS-CoV-2-associated encephalitis and meningitis amid COVID-19 pandemic

Table 3 Auxiliary examination of acute neurologic illness among patients with confirmed encephalitis/meningitis with evidence of severe acute respiratory syndrome coronavirus 2 infection

No.	Ref.	Chest radiogram	Blood test	CSF finding	SARS-CoV-2 in CNS	Neuroimaging	EEG
1	16	CT showed multiple subpleural ground glass opacities	Low WBC count (3.3 × 109/L) and lymphopenia (0.8 × 109/L)	WBC1 cell/mm3, protein 0.27 g/L, ADA 0.17 U/L and sugar 3.14 mmol/L; the evidence of bacterial or tuberculous infection (-)	Anti-SARS-CoV-2 IgM /IgG in CSF (-)	Skull CT was normal	N/A
2	9	CT showed that there was small ground glass opacity on the right superior lobe and both sides of the inferior lobe	High WBC, neutrophil dominant, relatively low lymphocytes; high CRP	Pressure was greater than 320 mmH2O, cell count 12 cells/mm3, mononuclear 10 cells/mm3 and polymorphonuclear 2 cells/mm3. Anti- HSV 1 and varicella-zoster IgM antibodies (-)	SARS-CoV-2 RNA in CSF (-)	MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporallobe and hippocampus	N/A
3	2	CT showed patchy bi-basilar consolidations	WBC 10.49 × 109/L, Neut 6.63 × 109/L, Lym 2.86 × 109/L, PLT 83 × 109/L; CRP 55 mg/L	WBC 960 cells/mm3, glucose 70 mg/dL, proteins 65.4 mg/dL; HSV/EBV/CMV/ VZV-DNA (-); enterovirus (-); Ab anti Ca++Channel/AMPA1, 2 /CASPR 2 /LGI1 (-); Ab anti NMDAR (+)	SARS-CoV-2 RNA in CSF (-)	Neuroradiology did not show significant findings	The EEG showed theta activity at 6 Hz, unstable, non-reactive to visual stimuli. No significant asymmetries were seen
4	17	N/A	N/A	N/A	SARS-CoV-2 RNA in Postoperative brain histopathology (+)	MRI showed hyperintense signal in the left temporal lobe in T2 and T2 FLAIR imaging	N/A
5	36	X-ray did not show any pathological findings	high WBC count 12.9 × 109/L; high procalcitonin 0.10 ng/mL; high D-dimer 0.790 mg/L	N/A	SARS-CoV-2 RNA PCR in CSF (+)	A right frontal intracerebral hematoma associated with subarachnoid hem orrhage in the ipsilateral sylvian fissure and frontal and temporal lobes; a thin, acute subdural hematoma was also evident. The hematoma appeared surrounded by edema and caused midline shift. Bilateral supratentorial leptomeningeal increased enhancement was detected	N/A
6	19	CT showed ground glass opacities in the bilateral inferior lobes	WBC count 5.96 × 109/L, lymphocytopenia 1.1 × 109/L, PLT 143 × 109/L; CRP 53.2 mg/L	N/A	N/A	MRI revealed an abnormal hyperintensity in the SCC on diffusion-weighted image	N/A
7	20	CT showed right lower lobe infiltrate	N/A	Pressure 30 cmH2O, nucleated 115 cells/mm3, erythrocytes 7374 cells/mm3, protein > 2 g/L; nucleated cell count remained strongly increased even after correction for the traumatic tap (approximately 1 nucleated cell/700 erythrocytes)	Markedly increased levels of IgM for SARS-CoV-2 S1 and E proteins in CSF, SARS-CoV-2 RNA in CSF (-)	MRI showed non-enhancing cerebral edema and diffusion weighted imaging abnormalities predominantly involving the right cerebral hemisphere, as well as brain herniation. An occlusive thrombus was identified in the right internal carotid artery, and edema was also identified in the cervical spinal cord	N/A
8	20	CT showed bilateral, diffuse ground glass infiltrates	N/A	Pressure 48 cm H2O, no pleocytosis, erythrocytes 27 cells/mm3, a mildly increased protein level	Markedly increased levels of IgM for SARS-CoV-2 S1, SARS-CoV-2 RNA in CSF (-)	MRI showed a non-enhancing hyperintense lesion within the splenium of the corpus callosum on fluid- attenuated inversion recovery and diffusion weighted imaging sequences	EEG showed diffuse slowing with a suggestion that the myoclonus was seizure-related
9	20	CT showed multifocal, patchy, ground glass opacities	N/A	Normal opening pressure; levels of nucleated cells, erythrocytes, and protein within reference levels; increased glucose level	Markedly increased levels of IgM for SARS-CoV-2 S1, SARS-CoV-2 RNA in CSF (-)	MRI showed an equivocal non-enhancing area of fluid-attenuated inversion recovery abnormality in the right temporal lobe	N/A
10	21	N/A	N/A	Red cell 921 cells/mm3, WBC 16 cells/mm3, neutrophils 8%, protein 0.97 g/L, glucose 92 mg/dL	SARS-CoV-2 RNA in CSF (-)	CT was negative	EEG noted frontal intermittent delta activity
11	22	CT showed multiple peripheral patchy ground-glass opacities	ANA = 2.7, positive; WBC 20 × 109/L, Neut 15 × 109/L, Lym 0.8 × 109/L, PLT 168 × 109/L; CRP 480 mg/L	Protein 0.19 g/L, glucose 61 mg/Dl with no white or red blood cells; HSV-DNA (-)	SARS-CoV-2 RNA in CSF (-)	MRI revealed T2- FLAIR high signal intensities in bilateral thalami, medial temporal and pons. Corresponding areas in T1 images were hypo-signal	N/A
12	37	CT was normal	Blood cell counts, transaminases, bilirubin, CPK, coagulogram, electrolytes, renal function, and CRP were all normal	WBC 1 cell/mm3, protein 0.32 g/L, glucose 68 mg/dL	SARS-CoV-2 RNA in CSF (+)	Brain MRI was normal; cervical spinal cord MRI showed a small left lateral ventral lesion with T2/STIR hypersignal, measuring about 0.4 cm in its sagittal plane	N/A
13	23	X-ray showed a right lower zone consolidation	WBC 7.0 × 109/L, lymphocytes 1.2 × 109/L; high CRP 50 mg/L; high GGT 107 U/L, high ALT 88 U/L	Protein 0.423 g/L with no rise in white cells and negative bacterial cultured	Low volume sample could be obtained and PCR for SARS-CoV-2 RNA was not possible	MRI of the brain and cervical spine suggested an inflammatory rhombencephalitis/myelitis, the increased signal lesion in the right inferior cerebellar peduncle, extending to a small portion of the upper cord. The lesion measured 13 mm in maximum cross-sectional area and 28 mm in longitudinal extent. There was swelling at the affected tissue and associated micro-haemorrhage	N/A
14	24	X-ray and CT were normal	WBC 7.1 × 109/L	white cells 70 cells/mm3 with 100% lymphocyte, protein 0.1 g/L, glucose 120 mg/dL	Unable to send CSF specimen for SARS-CoV-2 RNAPCR testing	CT of the head without contrast was normal	EEG showed generalized slowing with no epileptic discharges
15	25	N/A	N/A	Leukocyte 1 cell/mm3, protein 0.66 g/L, glucose 10.5 mmol/L	SARS-CoV-2 RNA in CSF (-)	MRI revealed hyperintensity of the right orbital prefrontal cortex adjacent to the olfactory bulb, which seemed to spread towards the right mesial prefrontal cortex and to the right caudate nucleus	EEG showed repetitive 1 Hz rhythmic bursts over the right frontal region, suggestive of a non-convulsive status epilepticus
16	26	CT showed multiple subpleural ground glass opacities	WBC 26.53 × 109/L, PLT 202 × 109/L; CRP 135 mg/L; D-dimer 6.27 mg/L; LDH 560 IU/L; IL-6 481 pg/mL; ferritin 1763 ng/mL	Protein 0.376 g/L, glucose 130 mg/dL, cell count 0, CSF IgG mg/L -, IgG index -, AlbQ -, oligoclonal band -	SARS-CoV-2 RNA in CSF (-)	MRI findings showing cortical or white matter hyperintensities, contrast enhancement, and sulcal hemorrhagic features, all of which are considered compatible with meningoencephalitis	N/A
17	26	CT showed multiple subpleural ground glass opacities	WBC 20.21 × 109/L, PLT 540 × 109/L; CRP 82.9 mg/L, D-dimer 6.6 mg/L, LDH 304 IU/L, IL-6 -pg/mL, ferritin 2918 ng/mL	Protein 0.732 g/L, glucose 201 mg/dL, cell count 0, CSF IgG mg/L 4.27, IgG index 0.330, AlbQ 13.5, oligoclonal band none	SARS-CoV-2 RNA in CSF (-)	MRI findings showing cortical or white matter hyperintensities, contrast enhancement, and sulcal hemorrhagic features	N/A
18	26	CT showed multiple subpleural ground glass opacities	WBC 17.081 × 109/L, PLT 140 × 109/L, CRP 32.7 mg/L, D-dimer 0.73 mg/L, LDH 414 IU/L, IL-6 -pg/mL, ferritin 896 ng/mL	Protein 0.657 g/L, glucose 121 mg/dL, cell count 0, CSF IgG mg/L 4.68, IgG index 0.45, AlbQ 8.87, oligoclonal band none	SARS-CoV-2 RNA in CSF (-)	MRI was normal	N/A
19	26	CT showed multiple subpleural ground glass opacities	WBC 11.49 × 109/L, PLT 660 × 109/L, CRP 142.2 mg/L, D-dimer 0.91 mg/L, LDH 271 IU/L, IL-6 -pg/mL, ferritin 612 ng/mL	Protein 0.131 g/L, glucose 120 mg/dL, cell count 0, CSF IgG 3.23 mg/L, IgG index 0.780, AlbQ 5.14, oligoclonal band none	SARS-CoV-2 RNA in CSF (-)	MRI was normal	N/A
20	26	CT showed multiple subpleural ground glass opacities	WBC 42.70 × 109/L, PLT 299 × 109/L, CRP 732.3 mg/L, D-dimer 6.97 mg/L, LDH 709 IU/L, IL-6 510 pg/mL, ferritin 5235 ng/mL	Protein 0.52 g/L, glucose 67 mg/dL, cell count 0, CSF IgG 6.66 mg/L, IgG index 0.380, AlbQ 14.1, oligoclonal band none	SARS-CoV-2 RNA in CSF (-)	MRI was normal	N/A
21	26	CT showed multiple subpleural ground glass opacities	WBC 17.83 × 109/L, PLT 664 × 109/L, CRP 431.8 mg/L, D-dimer 7.93 mg/L, LDH 1110 IU/L, IL-6 9192 pg/mL, ferritin 555 ng/mL	Protein 0.57g/L, glucose 59 mg/dL, cell count 0, CSF IgG 5.71 mg/L, IgG index 0.520, AlbQ 10.0, oligoclonal band none	SARS-CoV-2 RNA in CSF (-)	MRI findings showing cortical or white matter hyperintensities, contrast enhancement, and sulcal hemorrhagic features	N/A
22	33	X-ray and CT were normal	N/A	Bacterial culture and herpes simplex virus type 1 (-)	SARS-CoV-2 RNA in CSF (+)	N/A	N/A
23	27	X-ray showed moderate bilateral interstitial pneumonia	High D-dimer 0.968 mg/L	Lymphocytic pleocytosis 18 cells/mm3, protein 69.6 mg/dL; oligoclonal bands (-)	SARS-CoV-2 RNA in CSF (-)	MRI with gadolinium contrast did not reveal any significant alterations or contrast-enhanced areas	EEG exhibited generalized slowing, with decreased reactivity to acoustic stimuli
24	28	N/A	N/A	Protein 0.466 g/L, glucose 59 mg/dL, cell count 17 cells/mm3, lymphocyte 97%，anti-NMDA antibodies(-)	SARS-CoV-2 RNA in CSF (-)	MRI was normal	EEG revealed nonconvulsive, focal status epilepticus (abundant bursts of anterior low-medium voltage irregular spike-and waves superimposed on an irregularly slowed theta background); a follow-up EEG 24 h after admission showed a moderate theta background slowing, without epileptiform features
25	28	N/A	N/A	High lymphocytic pleocytosis, iral/bacterial pathogens (-)	SARS-CoV-2 RNA in CSF (-)	MRI was normal	N/A
26	29	N/A	CRP 44.8 mg/L; ferritin 1414 ng/mL; D-dimer 0.625 mg/L; LDH 1016 U/L	WBC count 8 cells/mm3; protein 0.2 g/L; oligoclonal band test (-)	SARS-CoV-2 RNA in CSF (-)	CT showed hypodensity of the splenium of the corpus collosum	EEG showed mild diffuse slowing
27	29	N/A	CRP 31.3 mg/L; ferritin 1192 ng/mL; D-dimer 0.494 mg/L; LDH 900 U/L	WBC count 2 cells/mm3; protein 0.19 g/L; oligoclonal band test (-)	SARS-CoV-2 RNA in CSF (-)	Axial T2 of MRI showed signal changes of the genu and corpus collosum (top) and bilateral centrum semiovale with restricted diffusion (bottom)	EEG showed diffuse slow activity
28	30	CT showed multiple ground-glass opacities with multiple fibrous cord-like shadows in both lungs	WBC 3.3 × 109/L, lymphocyte 24.4%; neutrophil 62.8%; CRP 10.74 mg/L	Pressure 200 cm H2O, cell count 1 cell/mm3, protein 0.275 g/L, glucose 3.14 mmol/L; chloride 123 mmol/L	SARS-CoV-2 RNA in CSF (-)	CT did not reveal significant abnormalities	N/A
29	31	CT showed multiple subpleural ground glass opacities	N/A	Bacteria/HSV type 1 and 2/varicella zoster virus/West Nile virus (-)	Unable to test SARS CoV-2 in the CSF	MRI showed acute necrotizing encephalitis were seen in the bilateral thalami, medial temporal lobes, and sub-insular regions	N/A
30	18	N/A	N/A	N/A	SARS-CoV-2 RNA in CSF (+)	CT was normal	N/A
31	33	N/A	D-dimer 1.8 mg/L	CSF matched oligoclonal band	SARS-CoV-2 RNA in CSF (-)	MRI brain normal	N/A
32	33	N/A	D-dimer 1.599 mg/L	CSF protein raised, oligoclonal band test (-)	SARS-CoV-2 RNA in CSF (-)	MRI brain: T2 hyperintense signal changes in upper pons, limbic lobes, medial thalami and subcorticalcerebral white matter	N/A

NA: Not available; CT: Computed tomography; EEG: Electroencephalography; CSF: Cerebrospinal fluid; MRI: Magnetic resonance imaging; FLAIR: Fluid-attenuated inversion recovery; WBC: White blood cell; N: Neutrophils; L: Lymphocyte; PLT: Platelet; CRP: C-reactive protein; GGT: Gamma glutamyl transferase; ALT: Alanine aminotransferase; SCC: Splenium of corpus callosum.