What is the recommended treatment for a patient with post-COVID (Coronavirus Disease 2019) encephalitis?

Treatment of Post-COVID Encephalitis

Post-COVID encephalitis should be treated with high-dose corticosteroids (methylprednisolone 1g IV daily or dexamethasone 6mg daily) combined with intravenous immunoglobulin (IVIG 2g/kg over 5 days), as this combination addresses the cytokine-mediated inflammatory pathophysiology and has shown clinical improvement in multiple case series. 1, 2, 3

Initial Management Approach

Immediate Supportive Care

• Ensure adequate oxygenation and respiratory support, as hypoxia contributes to encephalopathic changes and many patients require intubation for airway protection 1, 3
• Manage seizures aggressively with antiepileptic drugs (levetiracetam is commonly used) if present, as status epilepticus can occur 1
• Provide venous thromboembolism prophylaxis with anticoagulation, as COVID-19 patients are hypercoagulable with elevated D-dimer levels 1

Diagnostic Workup Specifics

• Obtain brain MRI with T2/FLAIR sequences looking for hyperintensity in white matter (44.68% of cases), temporal lobe (17.02%), and thalamus (12.76%) 2, 3
• Perform lumbar puncture to check for SARS-CoV-2 RNA by PCR in CSF (can be positive even when nasopharyngeal swab is negative), elevated protein, and to exclude HSV-1/2, VZV, and other viral etiologies 1, 2
• Monitor for elevated opening pressure (>25 cm H₂O has been reported) 1

Pharmacological Treatment Algorithm

First-Line Immunomodulatory Therapy

• Administer IV methylprednisolone 1g daily for 3-5 days (most commonly used regimen in case series) OR dexamethasone 6mg daily for up to 10 days 1, 2, 3, 4
• Add IVIG 2g/kg divided over 5 days to mitigate cytokine storm and reduce vasogenic edema 1, 3, 5, 4

Important nuance: The evidence base consists primarily of case reports and case series rather than RCTs, but the temporal correlation between treatment initiation and clinical improvement is consistent across multiple reports. The combination therapy targets both the inflammatory cascade and potential autoimmune mechanisms 2, 3

Antiviral Considerations

• Consider acyclovir 10mg/kg IV every 8 hours empirically until HSV encephalitis is excluded, as MRI findings can mimic herpes encephalitis (right mesial temporal hyperintensity) 1, 2
• Viral protease inhibitors (lopinavir/ritonavir, favipiravir) have been used in some cases but lack strong evidence and are NOT recommended by current guidelines 1

Adjunctive Therapies

• Broad-spectrum antibiotics (ceftriaxone, vancomycin) should be given empirically until bacterial causes are excluded 1
• Rituximab has been used successfully in isolated cases of COVID-19 encephalitis with good response 5

Monitoring and Response Assessment

Clinical Improvement Markers

• Expect improvement in hemiparesis/hemiplegia within 3-5 days of starting immunomodulatory therapy 3
• Repeat brain MRI to document decreased edema and resolution of inflammatory changes 3
• Monitor for complications including hemorrhagic transformation (11.42% show cerebral hemorrhages on CT) 2

Treatment Failure Protocol

• If no response to steroids and IVIG within 5-7 days, consider plasmapheresis as second-line therapy 4
• Escalate to rituximab for refractory cases based on limited case report evidence 5

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting CSF SARS-CoV-2 PCR results, as nasopharyngeal swabs can be falsely negative while CSF is positive 1
• Do not use hydroxychloroquine, as guidelines strongly recommend against it with no proven benefit 1, 6, 7
• Do not withhold corticosteroids due to concerns about viral replication—the inflammatory/cytokine storm mechanism predominates in encephalitis cases 1, 3
• Recognize that mortality is significant (28.26% in systematic review), requiring ICU-level monitoring 2

Pathophysiology Context

The mechanism involves cytokine storm causing hypoxic/metabolic insults, direct neurotropism of SARS-CoV-2, and potential autoimmune reactions with microglial activation 8, 3. The symmetric multifocal lesions with thalamic involvement on MRI T2/FLAIR represent acute necrotizing encephalopathy secondary to intracranial cytokine storm 3

Prognosis and Follow-Up

• Most cases show reversibility with prompt immunomodulatory treatment 2, 3
• Establish multidisciplinary rehabilitation addressing cognitive, physical, and psychological sequelae 8
• Monitor for post-COVID cognitive impairment ("brain fog") requiring 6-12 months of supportive care 8
• Screen for psychological complications (anxiety, depression, PTSD) which occur in >60% of severe COVID-19 patients 1