Long COVID Treatment
The treatment of long COVID centers on comprehensive rehabilitation, symptom-based supportive care, and energy conservation strategies, with all patients requiring screening for rehabilitation needs before hospital discharge or when experiencing persistent symptoms. 1, 2
Initial Assessment and Screening
All patients with suspected long COVID should be screened for rehabilitation needs across physical, cognitive, and mental health domains to facilitate timely referral and management. 1 This screening should occur both before hospital discharge and for those experiencing persistent symptoms after discharge, addressing physical deconditioning, respiratory function, swallowing difficulties, cognitive impairments, and mental health disorders. 1
Core Treatment Principles
Energy Conservation and Pacing
Pacing is the foundational intervention for managing postexertional malaise (PEM), and exercise is contraindicated for patients with PEM as it worsens symptoms in 75% of patients. 1, 2 Physical activity recommendations must be carefully tailored to current activity tolerance, as overly intense activity triggers PEM and worsened muscle damage. 2 Patients should resume daily activities conservatively at a safe, manageable pace with gradual increases based on symptoms. 1
Respiratory Symptom Management
For persistent breathlessness, provide education on breathing control techniques including high side lying, forward lean sitting, pursed lip breathing, and square box breathing. 1 Walking pace regulation should be implemented to reduce breathlessness and prevent oxygen desaturation on exertion. 1
For persistent pulmonary symptoms with organizing pneumonia patterns (persistent symptoms, functional abnormalities, and CT abnormalities 6 weeks post-discharge), corticosteroids at 0.5mg/kg prednisolone for 3 weeks showed symptomatic improvement, increased gas transfer and forced vital capacity, and radiologic improvement in small studies. 1 However, the ESCMID guidelines state that evidence is insufficient to provide a recommendation for or against corticosteroids for persistent pulmonary symptoms, as some patients demonstrate significant spontaneous recovery within 12 weeks. 1
Mental Health and Psychological Support
All patients should receive basic mental health and psychosocial support by addressing their needs and concerns, with continuation after hospital discharge. 1 For anxiety, fear, depression, and somatization symptoms, psychological counseling, mental health education, cognitive behavioral therapy, mindfulness training, and group interventions are recommended. 1
For mild adverse mental states, psychological self-adjustment including breath relaxation training and mindfulness training is recommended. 1 For moderate to severe adverse mental states, intervention combining medication and psychotherapy is suggested, with medications having short half-lives and low drug-drug interaction risk at the lowest possible dose and shortest duration. 1
Symptom-Specific Pharmacological Options
Dysautonomia and POTS
For postural orthostatic tachycardia syndrome (POTS), β-blockers, pyridostigmine, fludrocortisone, and midodrine are pharmacological options. 1 Non-pharmacological interventions include increasing salt and fluid intake, intravenous salt administration, and compression stockings. 1
Stellate ganglion block has shown promise for dysautonomia symptoms in case reports, though effects may wane over time requiring repeated procedures. 1, 3 Current evidence is limited to case reports and small studies rather than large randomized trials. 3
Neuroinflammation and Immune Dysfunction
Low-dose naltrexone shows promise for neuroinflammation and has been used successfully in ME/CFS and long COVID. 1 Intravenous immunoglobulin can be considered for immune dysfunction, with consultation from an immunologist recommended for implementation. 1
Antihistamines and Mast Cell Activation
H1 and H2 antihistamines, particularly famotidine following mast cell activation syndrome protocols, are used to alleviate a wide range of symptoms, though they are not curative. 1
Anticoagulation
Triple anticoagulant therapy showed resolution of symptoms in all 24 patients in one study, addressing abnormal clotting patterns. 1 However, this requires careful patient selection and monitoring.
Emerging and Investigational Treatments
Paxlovid showed a 25% reduction in long COVID incidence when used for acute COVID-19 treatment, and a case report noted resolution of long COVID following Paxlovid treatment. 1 This warrants further investigation for both prevention and treatment.
Other treatments under investigation include:
- BC007 for neutralizing G protein-coupled receptor autoantibodies 1
- Apheresis for removing microclots and reducing autoantibodies 1
- Sulodexide for endothelial dysfunction 1
- Probiotics for gastrointestinal and non-gastrointestinal symptoms 1
- Pycnogenol for reducing oxidative stress and improving quality of life 1
Rehabilitation Interventions
Rehabilitation should be implemented as soon as possible in parallel with disease treatment, initiated by rehabilitation professionals in the acute phase when oxygenation and hemodynamics are stable. 1 Pulmonary rehabilitation training is suggested for impaired pulmonary function and potential pulmonary fibrosis. 1
Non-pharmacological interventions including Baduanjin, Tai Chi, 6-character breathing exercises, posture management, and breathing exercise management are recommended. 1
Critical Caveats
Exercise, cognitive behavioral therapy, and graded exercise therapy are contraindicated for patients with postexertional malaise. 1 This is a critical distinction from other post-viral conditions and represents a common pitfall in management.
No positive COVID-19 test during acute infection is required to diagnose long COVID, and no single laboratory finding is definitively diagnostic. 2 Treatment recommendations should be delivered with humility given the many persistent unknowns related to long COVID. 2
Medications must be used cautiously, prioritizing patient preference through shared decision-making and avoiding medications that may improve some symptoms (e.g., cognitive impairment) while worsening others (e.g., PEM). 2