Positives

• Esketamine may be relevant for Long COVID or ME/CFS patients whose illness includes severe depression, suicidality, trauma symptoms, or treatment-resistant mood symptoms (Johns Hopkins).
• For those patients, addressing mood and nervous-system distress can be part of quality-of-life care even if it does not treat the underlying post-viral illness (NAMI).

Negatives

• Esketamine should not be framed as a treatment for PEM, dysautonomia, MCAS, Lyme, or the core fatigue/brain-fog biology of Long COVID or ME/CFS (PMC).
• Dissociation, sedation, blood-pressure increases, nausea, and post-treatment fatigue may be hard for sensitive patients (AAFP).

Hurdles & Side Effects

• Spravato requires certified-clinic administration, monitoring after each dose, and transportation home (Mayo Clinic).
• Access is usually tied to treatment-resistant depression criteria and insurance requirements, not chronic illness symptoms alone (Johns Hopkins).