What is the treatment for Covid-19 (Coronavirus disease 2019) encephalitis?

Treatment of COVID-19 Encephalitis

For COVID-19-associated encephalitis, we recommend treatment with intravenous immunoglobulin (IVIG) combined with corticosteroids (methylprednisolone or dexamethasone), with consideration of IL-6 receptor antagonist therapy (tocilizumab) in cases with evidence of hyperinflammatory response. 1, 2

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis through:

• RT-PCR testing of nasopharyngeal swabs for SARS-CoV-2 1, 3
• Cerebrospinal fluid (CSF) analysis showing lymphocytic pleocytosis (typically >20 cells/µL with >90% lymphocytes) and elevated protein (often >100 mg/dL) 1, 2, 4
• Brain MRI to identify characteristic patterns including temporal lobe hyperintensity (17%), white matter involvement (45%), thalamic changes (13%), and frontal lobe abnormalities 1, 5, 3
• CSF RT-PCR for SARS-CoV-2 when available, though this is frequently negative even in confirmed cases 1, 2, 3

Primary Treatment Regimen

Immunomodulatory Therapy

Intravenous Immunoglobulin (IVIG) is the cornerstone treatment:

• IVIG mitigates severe cytokine storming and alleviates secondary vasogenic edema 1
• Multiple case reports demonstrate successful outcomes with IVIG therapy 2, 6, 4

Corticosteroids should be administered concurrently:

• Intravenous methylprednisolone is preferred for acute encephalitis 1, 4
• Dexamethasone is an alternative, particularly in patients with concurrent severe COVID-19 pneumonia 4
• Corticosteroids are strongly recommended for hospitalized COVID-19 patients requiring oxygen or ventilatory support 1

IL-6 Receptor Antagonist Therapy

Tocilizumab should be considered in specific circumstances:

• Patients with evidence of hyperinflammatory response (elevated IL-6, ferritin, D-dimer) 2
• Those requiring oxygen or ventilatory support 1
• Particularly effective when initiated within 24 hours of requiring noninvasive or invasive ventilatory support 1
• Should be given in addition to corticosteroids, not as monotherapy 1

Adjunctive Treatments

Antiviral Therapy

Acyclovir should be administered empirically:

• Given initially to cover HSV encephalitis until excluded by testing 1, 5
• Commonly used alongside other treatments (16.7% of reported cases) 5

Favipiravir or other viral protease inhibitors may be considered:

• Historical use included lopinavir/ritonavir, though these are no longer recommended 1
• Current evidence does not support routine antiviral use specifically for encephalitis 1

Seizure Management

Antiepileptic drugs for patients presenting with seizures:

• Levetiracetam is commonly used as first-line therapy 1
• Seizures occur in approximately 22% of COVID-19 encephalitis cases 5, 3
• Status epilepticus requires aggressive management with standard protocols 1

Anticoagulation

Prophylactic anticoagulation is recommended:

• All hospitalized COVID-19 patients should receive thromboprophylaxis 1
• COVID-19 creates a hypercoagulable state with elevated D-dimer levels 1

Monitoring and Supportive Care

• Continuous monitoring in ICU setting for severe cases requiring mechanical ventilation 1
• Electroencephalography (EEG) shows diffuse slow waves in 80% of cases 3
• Serial neuroimaging to assess progression or complications 1
• Adequate nutrition and fluid support to maintain water-electrolyte balance 1

Important Caveats

Avoid these interventions:

• Hydroxychloroquine is not recommended for COVID-19 patients, including those with encephalitis 1
• Azithromycin should not be used in absence of bacterial infection 1
• Remdesivir has no established role in COVID-19 encephalitis management 1

Critical timing considerations:

• Neurological symptoms typically appear approximately 8 days after initial COVID-19 symptoms 3
• Post-infectious encephalitis can occur 1-2 weeks after apparent recovery from acute COVID-19 4
• Early recognition and treatment initiation improves outcomes 2, 6

Expected Outcomes

• Approximately 66-88% of patients improve with appropriate systemic therapy 5, 3
• Mortality rate is approximately 28% in hospitalized cases 5
• Full recovery is possible with aggressive immunomodulatory treatment 2, 6
• Some patients may develop post-infectious encephalitis requiring prolonged immunosuppressive therapy 4