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

Table 1 Demographic and clinical characteristics of acute neurologic illness among patients with confirmed encephalitis/meningitis with evidence of severe acute respiratory syndrome coronavirus 2 infection

No.	Ref.	Age/Sex	Area	Past medical history	Viral syndrome	Diagnosis of COVID-19	TVC (d)	Neurological symptoms	Neurological signs	TVN (d)	Subtype	Primary target	Treatment	Outcome
1	16	NA/male	China	N/A	Fever, shortness of breath, myalgia	(+) RT-PCR/PS	N/A	Consciousness confusion	(+) Meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign) and extensor plantar response	14	ME	N/A	Supportive therapy (mannitol infusion, oxygen therapy), arbidol	Good: Consciousness was completely clear, hospital discharged
2	9	24 yr/male	Japan	N/A	Headache, fatigue, fever	(-) RT-PCR/NPS	N/A	Consciousness disturbance, seizures	(+) Neck stiffness	9	ME	Right lateral ventricle, mesial temporal lobe, hippocampus	N/A	N/A
3	2	23 yr/male	Italy	Substance abuse	Psychomotor agitation, thought disorganization, persecutory delusions, auditory hallucinations, anxiety, insomnia	(+) RT-PCR/PS	N/A	Dysphagia, dyskinesias, autonomic instabilities	Non responsive to commands, non-verbal, despite being able to move all his extremities and reacting to noxious stimuli	8	E	N/A	High doses of DEX, IVIg	Good: Clinical conditions are ameliorating
4	17	35 yr/female	Turkey	N/A	Mild flu-like complaints	(+) RT-PCR/PS	N/A	Headache, nausea, dizziness, seizure	N/A	14	E	Left anterior temporal lobe	Left anterior temporal lobectomy	Good: No post-operative neurological deficits, symptoms improved completely
5	36	36 yr/male	United Arab Emirates	N/A	Fever, headache, myalgia, cough, diarrhea, vomiting	(+) RT-PCR/PS	5	Drowsiness, consciousness confusion	(+) Mild neck stiffness	5	ME	Supratentorial leptomeningeal, right frontal lobe	N/A	Poor: The patient’s neurological symptoms was not improved
6	19	75 yr/male	Japan	Alzheimer’s disease	Diarrhea	(+) RT-PCR/PS	6	Left hand kinetic tremor, walking instability, urinary incontinence	(+) Finger-to-nose test; (+) ataxic gait was observed	6	E	Corpus callosum	Sulbactam/ampicillin, favipiravir, corticosteroid pulse, ciclesonide, meropenem	Dead
7	20	31 yr/female	United States	Sickle cell disease	Progressive dyspnea	(+) RT-PCR/NPS	5	Paralysis	Coma	11	EM	Right cerebral hemisphere, cervical spinal cord	Hydroxychloroquine, peramivir	Dead
8	20	34 yr/male	United States	Hypertension	Fever, shortness of breath, cough	(+) RT-PCR/NPS	2	Consciousness disturbance, myoclonus	Absent corneal and gag reflexes, absent withdrawal to painful stimuli	9	E	Corpus callosum	Hydroxychloroquine	N/A
9	20	64 yr/male	United States	Hypertension	Cough, dyspnea, fever	(+) RT-PCR/NPS	N/A	Myoclonus	Absent oculocephalic reflex and withdrawal to pain, diminished deep tendon reflexes	N/A	E	Right temporal lobe	Hydroxychloroquine	Good: Hospital discharged without major neurologic sequelae
10	21	11 yr/male	United States	N/A	Generalized weakness, fever	(+) RT-PCR/PS	3	Status epilepticus	N/A	3	E	Frontal lobe	Anticonvulsant medications	Good: Recovery
11	22	39 yr/female	Iran	N/A	Fever, myalgia, dry cough	(+) Anti-SARS- CoV-2-IgM, IgG in serum	10	Drowsiness, decline unconsciousness, seizure, headaches	N/A	10	E	Temporal lobe, pontine, thalami	Broad-spectrum IV antibiotics, hydroxychloroquine, atazanavir, IVIg, levetiracetam, methylprednisolone	Good: Normal consciousness, no diplopia or other abnormal findings
12	37	42 yr/female	Brazil	N/A	Coryza, nasal obstruction	(-) RT-PCR/NPS	N/A	Paresthesias (left upper limb, left hemithorax, and hemiface)	Hypoesthesia in left upper limb, left hemithorax, and hemiface	21	EM	Cervical spinal cord	Corticosteroids	Good: Recovery
13	23	40 yr/male	United Kingdom	Hypertension, glaucoma	Fever, progressive dyspnea, cough, diarrhea	(+) RT-PCR/NPS	11	Unsteady gait, diplopia, oscillopsia, limb ataxia, altered sensation in right arm, hiccups and dribbling when eating or drinking	Facial weakness, reduced tongue movements, limb ataxia	13	RE, myelitis	Brain stem; cervical spine	Gabapentin	Good: Neurological symptoms improved steadily and hospital discharged
14	24	41 yr/female	United States	Diabetes	Headache, fever	(+) RT-PCR/PS	3	Headache, seizure	(+) Neck stiffness, photophobia	2	ME	N/A	Antibiotics, acyclovir, anti-epileptic medication, hydroxychloroquine	Good: The patient's mentation improved and was able to ambulate, eat and use the bathroom, but the hallucinations remained intermittently
15	25	69 yr/male	France	Diabetes, hypertension	Cough, fever, anosmia	(+) RT-PCR/tracheal aspirate	5	Status epilepticus	N/A	5	E	Right frontal lobe	IVIg	Good: Improved
16	26	49 yr/male	Turkey	N/A	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter, cortical	Plasmapheresis treatment, LOP/RIT, AZI, CEF	Good: Consciousness was improved
17	26	59 yr/male	Turkey	Hypertension	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter, cortical	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
18	26	59 yr/male	Turkey	Hypertension, diabetes, obesity	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Dead: Cardiac arrest
19	26	51 yr/female	Turkey	Hypertension, diabetes	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
20	26	55 yr/male	Turkey	Hypertension	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	M	N/A	Plasmapheresis treatment, AZI, HC, FAV	Poor: Subsequent infection
21	26	22 yr/male	Turkey	Autism	Dyspnea	(+) RT-PCR/PS	N/A	Consciousness disturbance, delirium	N/A	N/A	E	White matter	Plasmapheresis treatment, AZI, HC, FAV	Good: Consciousness was improved
22	33	40 yr/female	United States	Obesity, diabetes mellitus	Fever	(+) RT-PCR/NPS	N/A	Syncope	N/A	1	E	N/A	Hydroxychloroquine	Good: Recovery without neurological deficits
23	27	60 yr/male	United Kingdom	N/A	Fever, cough, cognitive fluctuations	(+) RT-PCR/NPS	5	Irritability, confusion, asthenia, consciousness	(+) Palmomental and glabella reflexes, mutism, (+) moderate nuchal rigidity, severe akinetic syndrome	1	E	N/A	Lopinavir/ritonavir, hydroxychloroquine, ampicillin, acyclovir	Good: Normal neurological examination and hospital discharged
24	28	64 yr/female	Switzerland	N/A	Weakness, cough, myalgia	(+) RT-PCR/NPS	N/A	Tonico-clonic seizure	Disoriented, attention deficit, bilateral grasping, psychotic symptoms (hyper-religiosity with mystic delusions, visual hallucinations), averbal and motor perseverations	6	E	N/A	Clonazepam, valproate, acyclovir	Good: Improved
25	28	67 yr/female	Switzerland	N/A	Cough	(+) RT-PCR/NPS	N/A	Headache, syncope	Motor perseverations, bilateral grasping, aggressiveness, left hemianopia and sensory hemineglect	18	E	N/A	Ceftriaxone, amoxicillin, acyclovir	Good: Neurological symptoms resolved, except for a mild headache, hospital discharged
26	29	8 yr/male	South Asian	N/A	Fever, abdominal pain, palmar rash, vomiting	(+) RT-PCR/NPS	N/A	Confused, agitated, headache	(+) Meningeal irritation signs (including nuchal rigidity, Kernig sign and Brudzinski sign), generalized proximal weakness	1	ME	Corpus callosum	IVIg, dexamethasone, anakinra	Poor: Still inpatient, wheelchair bound
27	29	9 yr/male	Caribbean	N/A	Fever, palmar rash, vomiting	(+) RT-PCR/NPS	N/A	Confused, ataxia, dysarthria, headache	Urinary retention, bilateral proximal leg weakness	1	E	Corpus callosum	N/A	Good: Hospital discharged
28	30	64 yr/male	China	Health	Fever, cough	(+) RT-PCR/PS	15	Lethargic, unresponsive	(+) Meningeal irritation signs (nuchal rigidity, Kernig sign, Brudzinski sign), consciousness alternating between lethargy and irritability, responses to questions were incorrect, (+) ankle clonus, Babinski sign and Chaddock sign	14	M	N/A	Oxygen inhalation, arbidol, ribavirin, traditional Chinese medicine	Good: Clear consciousness, limb reflexes were relatively active, left lower limb was positive for pathological signs
29	31	50 yr/female	United States	N/A	Cough, fever	(+) RT-PCR/PS	2	Altered mental status	N/A	2	E	Thalami, temporal lobe, insular lobe	IVIg	N/A
30	18	56 yr/male	China	N/A	N/A	(+) RT-PCR/PS	N/A	Consciousness confusion	N/A	N/A	M	N/A	N/A	Good: Neurological symptoms gradually disappeared
31	33	65 yr/female	United Kingdom	N/A	N/A	(+) RT-PCR/NPS	N/A	Reducedconsciousness	N/A	N/A	E	N/A	1 g IVMP 3 d, oral prednisolone taper, levetiracetam, clonazepam	Poor: Incomplete, partial recovery
32	33	66 yr/female	United Kingdom	N/A	N/A	(+) RT-PCR/NPS	N/A	Reducedconsciousness	N/A	N/A	E	Upper pons, limbic lobes, medial thalami, subcortical cerebral white matter	1 g IVMP 3 d then oral prednisolone taper, IVIg	Poor: Incomplete, partial recovery

NA: Not available; M: Male; F: Female; (+): Positive; TVC: Time between reported viral syndrome and confirmed coronavirus disease-19; TVN: Time between reported viral syndrome and onset of neurological symptoms (d); PS: Pharyngeal swab; NPS: Nasopharyngeal swab; E: Encephalitis; M: Meningitis; ME: Meningoencephalitis; EM: Encephalomyelitis; RE: Rhombencephalitis; WBCs: White blood cells; CRP: C-reactive protein; LDH: Lactate dehydrogenase; CSF: Cerebrospinal fluid; LOP: Lopinavir; RIT: Ritonavir; AZI: Azitromisin; HC: Hydroxychloroquine; CEF: Ceftriaxone; FAV: Faviripavir; IL-6: Interleukin-6; MRI: Magnetic resonance imaging; AlbQ: Albumin quotient; IVIg: Intravenous immune globulin.

Table 2 Clinical and demographic characteristics of the 32 coronavirus disease-19 patients with encephalitis/meningitis

Characteristic	Value (n = 32)
Median age (range), yr	45.37 (8-75)
Male sex, n (%)	20 (62.5)
Female sex, n (%)	12 (37.5)
Time between reported viral syndrome and confirmed COVID-19 (n = 12)	6 (2-15)
General symptoms before the onset of the encephalitis/meningitis, n (%)	29 (96.67)
Fever	16 (55.17)
Cough	13 (44.83)
Dyspnea	11 (37.93)
Diarrhea	4 (13.79)
Myalgia	4 (13.79)
Generalized weakness	3 (10.34)
Headache	3 (10.34)
Vomiting	3 (10.34)
Nasal obstruction	2 (6.90)
Palmar rash	2 (6.90)
Abdominal pain	1 (3.45)
Anosmia	1 (3.45)
Cognitive fluctuations	1 (3.45)
Insomnia	1 (3.45)
Psychological abnormalities	1 (3.45)
Time between reported viral syndrome and onset of neurological symptoms	7.91 (1-21)
Neurological symptoms, n (%)	32 (100)
Consciousness disturbance	19 (59.38)
Seizure	7 (21.88)
Delirium	6 (18.75)
Headache	6 (18.75)
Altered mental status	3 (9.38)
Ataxia	2 (6.25)
Drowsiness	2 (6.25)
Dysphagia	2 (6.25)
Myoclonus	2 (6.25)
Paresthesias	2 (6.25)
Syncope	2 (6.25)
Unsteady gait	2 (6.25)
Autonomic instabilities	1 (3.13)
Diplopia	1 (3.13)
Dizziness	1 (3.13)
Dysarthria	1 (3.13)
Dyskinesias	1 (3.13)
Kinetic tremor	1 (3.13)
Nausea	1 (3.13)
Oscillopsia	1 (3.13)
Paralysis	1 (3.13)
Urinary incontinence	1 (3.13)
SARS-CoV-2 infection diagnostic category, n (%)
Nasopharyngeal swab/PT-PCR	28 (87.5)
SARS-CoV-2 IgM (Serum)	1 (3.13)
SARS-CoV-2 IgG (Serum)	1 (3.13)
Tracheal aspirate/PT-PCR	1 (3.13)
PCR for SARS-CoV-2 on CSF	4 (12.5)
PCR for SARS-CoV-2 in Postoperative brain histopathology	1 (3.13)
SARS-CoV-2 antibody (CSF)	3 (9.38)

COVID-19: Coronavirus disease-19; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; RT-PCR: Reverse transcriptase-polymerase chain reaction; CSF: Cerebrospinal fluid.

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.

Table 4 Auxiliary examination of the 32 coronavirus disease-19 patients with encephalitis/meningitis

Characteristic	Value (n = 32)
Subtype, n (%)
Encephalitis	19 (59.36)
Meningitis	5 (15.63)
Meningoencephalitis	5 (15.63)
Encephalomyelitis	2 (6.25)
Rhombencephalitis	1 (3.13)
Myelitis	1 (3.13)
Primary target identified by neuroimaging, n (%)
Temporal lobe	5 (15.63)
White matter	4 (12.5)
Corpus callosum	3 (9.38)
Frontal lobe	3 (9.38)
Cervical spinal cord	3 (9.38)
Thalami	3 (9.38)
Cortical	2 (6.25)
Limbic lobe	1 (3.13)
Brain stem	1 (3.13)
Upper pons	1 (3.13)
Hippocampus	1 (3.13)
Insular lobe	1 (3.13)
Lateral ventricle	1 (3.13)
Leptomeningeal	1 (3.13)
Pontine	1 (3.13)
Right cerebral hemisphere	1 (3.13)
Supratentorial	1 (3.13)
Chest radiogram, n (%)
Negative/total	4/22 (18.18)
Positive/total	18/22 (81.82)
Not available/total	8/30 (26.67)
Blood test, n (%)
WBC count (low/normal)	6/21 (28.57)
WBC count (high)	10/21 (47.62)
Lymphopenia (low)	4/21 (19.05)
CRP (high)	14/21 (66.67)
D-dimer (high)	12/21 (57.14)
Ferritin (high)	8/21 (38.1)
IL-6 (high)	1/21 (4.76)
procalcitonin (high)	1/21 (4.76)
ANA (positive)	1/21 (4.76)
N/A	11 (3.13)
Results of CSF analysis, n (%)
Increased pressure /total	2/5 (40)
Increased protein level /total	13/22 (59.09)
Increased white-cell count level/total	9/23 (39.13)
Ab anti NMDAR (positive), n (%)	1 (3.13)
Oligoclonal band test (positive), n (%)	1 (3.13)
Neuroimaging, n (%)
Negative/total	12/31 (38.71)
Positive/total	19/31 (61.29)
Not available	1 (3.13)
Results of EEG, n (%)
Diffuse slow wave/total	8/10 (80)
Focal epileptic wave/total	2/10 (20)
Generalized delta activity/total	1/10 (20)
N/A	20 (62.5)
Treatment modality, n (%)
Antibiotics/total	22/28 (78.57)
Antiretroviral drug/total	14/28 (50)
Hydroxychloroquine/total	12/28 (42.86)
Corticoid/total	7/28 (25)
IVIg/total	6/28 (21.43)
Plasmapheresis treatment/total	6/28 (21.43)
Anticonvulsant medications/total	6/28 (21.43)
Surgery/total	1/28 (3.57)
Interleukin-1 receptor antagonist/total	1/28 (3.57)
Traditional Chinese medicine/total	1/28 (3.57)
Not available/total	4/32 (12.5)
Outcome and prognosis, n (%)
Good	21/32 (65.63)
Poor	5/32 (15.64)
Dead	3/32 (9.38)
Not available	3/32 (9.38)

WBC: White blood cell; CRP: C-reactive protein; IL-6: Interleukin-6; CSF: Cerebrospinal fluid; EEG: Electroencephalography; IVIg: Intravenous immune globulin.