Diagnostic and therapeutic protocol for long COVID and post-vaccination syndrome

Basic diagnostics

Laboratory

Treatment and advice, basics

• Exercise intolerance: Physical therapy and/or occupational therapy to learn pacing (not graded exercise therapy!)
• Mast cell activation syndrome (MCAS): Trial therapy: Fexofenadine 120-180 mg, H2 blockers; Daosin with meals (if food intake has a significant effect)
  If there is no response to fexofenadine, try ketotifen, cromoglicic acid (3 x 200 mg) or alpha-lipoic acid (2 x 200-600 mg) [ii]
• Nutritional advice: try a low-histamine diet for a few weeks
• Try dietary supplements: L-arginine 5 g 1-0-0 (with herpes reactivation, add L-lysine 1-3 g); liposomal vitamin C 500 mg 1-0-1[iii]; nattokinase 2000-8000 FU in the morning on an empty stomach; niacin “no flush” formulation 250-500 mg in the morning; vitamin D 1000-3000 IU/day (target >120 nmol/L); L-tryptophan 500 mg 1-0-1 on an empty stomach; N-acetylcysteine 600 mg 1-0-1; Zinc 15 mg 0-0-1; selenium 50 µg 1-0-0; quercetin 250-500 mg 1-0-1[iv]
  
• COVID-19 vaccination leads to an improvement in symptoms in about 25% of people with long COVID and can therefore be tried (not in post-vaccination cases!) [v]
  
• Detailed advice on protection against further infection (wear FFP2 masks consistently in public indoor spaces; ensure good indoor air quality (ideally: air filters and regular ventilation!), if possible also in the classrooms of children of those affected; self-test before meetings)

Therapy escalation

• Sensory or vegetative disorder: Referral to the neurology department of a central hospital to test for small fiber neuropathy [ix]
  
• Low dose naltrexone: Dissolve 1 tablet of naltrexone 50 mg in 50 ml of water (1 mg naltrexone/ml solution). Start with 0.5 ml in the evening, increase by 0.5 ml every 1-2 weeks to at least 1.5-2.5 ml, maximum 5 ml. If insomnia occurs as a side effect, take in the morning [x]
  
• Low dose aripiprazole: Aripiprazole 1 mg/ml: Start with 0.1-0.25 ml daily, increasing by 0.1-0.25 ml every 1-2 weeks to a maximum of 2.0 ml. Take for several weeks [xi]
  
• Systemic corticosteroids: Prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days [xii]
  
• For hypocortisolism, fludrocortisone 0.1-0.2 mg, possibly with 10-37.5 mg cortisone (equivalent) daily; consider endocrinological evaluation
• Hyperbaric oxygen therapy [xiii]
  
• Intravenous immunoglobulins, HELP apheresis, immunoadsorption [xiv]
  
• Anticoagulation: Aspirin 75 mg, clopidogrel 75 mg, and apixaban 2 x 5 mg combined with pantoprazole 40 mg. Caution: Inform patient about risk of bleeding, monitor closely! [xv]
  

Treatment of specific symptoms

• Anosmia, dysosmia: Structured smell training: smell scents (rose, lemon, eucalyptus, and clove) for 30 seconds in the morning and evening and imagine the scent [xvi]. Medication: Zinc 2 x 50 mg, 1 puff of fluticasone nasal spray in each nostril or 32 mg methylprednisolone p.o. in the morning for 10 days [xvii] [xviii], or vitamin A nasal drops 10,000 IU/day for 8 weeks [xix]
  
• Fatigue, brain fog: D-ribose 1-3 x 5-10 g (not for diabetes mellitus) [xx]
  
• Insomnia: Diphenhydramine 3-25 drops at night (a low dose is usually sufficient), melatonin 3-10 mg at night (often positive effect on brain fog), QUVIVIQ 25-50 mg 30 minutes before bedtime.
• Cardiac symptoms: always check for and treat POTS/postural hypotension. If the response is unsatisfactory, perform cardiological diagnostics, consider cardiac 3T MRI to diagnose myocarditis [xxi]
  
• Dyspnea: POTS/postural hypotension? Respiratory physiotherapy. Try treatment with montelukast [xxii]. Pulmonary evaluation, possibly VQ-SPECT/CT to check for ventilation or perfusion defects [xxiii]
  
• Cognitive deficits: POTS/postural hypotension? Bupropion 150–300 mg [xxiv]. Trial therapy with 1 mg guanfacine (Intuniv®) and 600 mg N-acetylcysteine at night; increase guanfacine (Intuniv®) to 2 mg after one month [xxv]. MRI of the brain to rule out other causes. Neuropsychological assessment for objectification, possibly [18F]-FDG-PET to detect regional hypometabolism [xxvi]. Maybe try neurofeedback
  
• Pain:
  
• • Duloxetine 30-60 mg, amitriptyline or trimipramine 10-25 mg at night (not available in Switzerland: milnacipran)
  • Pregabalin 25-50 mg at night, if tolerated, increase dose to max. 300 mg daily, divided into three doses (smaller doses during the day)
  • Oxcarbazepine (start with 150 mg at night, increase to 2 x 600 mg) or lamotrigine (start with 25 mg in the morning, increase by 25 mg every two weeks to 3 x 100 mg; caution: exanthema, especially if the dose is increased too quickly!), alone or in combination with pregabalin
  • Topiramate, especially in cases of obesity (start with 25 mg at night, increase by 25 mg weekly up to 2 x 50-100 mg)
  • Tizanidine (2 mg at night, increase up to 2 x 4 mg), tramadol up to 4 x 50 mg, lidocaine patch for local pain
  • For pain patients with positive ANA test results, Plaquenil (caution: evaluate effectiveness only after several months)
  • Methadone or MST Continus® [xxvii]
    
• Digestive problems: Mast cell activation syndrome? Fexofenadine 120-180 mg daily, H2 blockers, Daosin with meals, nutritional counseling (low-histamine diet). Probiotics. If gastroscopy or colonoscopy is performed, histology with staining for mast cells (CD117) [xxviii]