From the Guidelines
The most up-to-date algorithm for diagnosis and treatment of Long COVID involves a symptom-based approach, with a comprehensive assessment including detailed history, physical examination, and targeted laboratory tests, and treatment is primarily symptomatic and multidisciplinary. The diagnosis typically requires a history of confirmed or suspected COVID-19 infection followed by persistent symptoms lasting beyond 12 weeks that cannot be explained by alternative diagnoses 1. According to the most recent study in 2023, diagnostic tools for Long COVID are mostly in development, and the results for patients with Long COVID are often normal using standard care tests 2.
Diagnostic Approach
The diagnostic approach should include:
- Detailed history
- Physical examination
- Targeted laboratory tests, such as complete blood count, comprehensive metabolic panel, thyroid function, C-reactive protein, and D-dimer 1
- Consideration of symptom-specific testing and diagnostic recommendations from the ME/CFS community 2
Treatment Approach
The treatment approach should be individualized and targeted to specific symptom clusters, with a focus on symptomatic relief and improvement of quality of life.
- For fatigue, a gradual pacing approach is recommended with careful activity management
- Respiratory symptoms may benefit from breathing exercises and pulmonary rehabilitation
- Cognitive dysfunction ("brain fog") can be addressed with cognitive rehabilitation strategies
- For cardiovascular symptoms like postural orthostatic tachycardia syndrome (POTS), increased fluid and salt intake, compression garments, and medications like beta-blockers (propranolol 10-20mg twice daily) may help
- Pain management typically involves acetaminophen or NSAIDs, with gabapentin (starting at 300mg daily and titrating up) for neuropathic pain
- Sleep disturbances may respond to sleep hygiene measures and sometimes low-dose melatonin (1-3mg)
- Mental health support is crucial, with cognitive behavioral therapy showing benefit 2
Emerging Treatments
Emerging treatments that may be worth exploring include:
- Low-dose naltrexone for neuroinflammation
- Intravenous immunoglobulin for immune dysfunction
- H1 and H2 antihistamines for mast cell activation syndrome
- BC007 for autoimmunity
- Anticoagulant regimens for abnormal clotting
- Apheresis for removal of microclots
- Supplements such as coenzyme Q10 and D-ribose
- Paxlovid for prevention and treatment of Long COVID 2
From the Research
Diagnosis of Long COVID
- The diagnosis of Long COVID is based on a comprehensive evaluation, including medical history, physical examination, blood tests, imaging studies, and functional tests 3.
- A positive COVID-19 test during acute SARS-CoV-2 infection is not required to diagnose Long COVID, and currently, there is no single laboratory finding that is definitively diagnostic for confirming or ruling out the diagnosis of Long COVID 4.
- The National Academies of Sciences, Engineering, and Medicine define Long COVID as "an IACC that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems" 4.
Treatment of Long COVID
- Current management strategies focus on symptom-based supportive care, including energy conservation strategies and addressing comorbidities and modifiable risk factors 4.
- Treatment recommendations should be delivered with humility, and medication use generally follows standard practice regarding indications and dosing, with extra attention to prioritize patient preference via shared decision-making and cautious use of medications that may improve some symptoms but may worsen other symptoms 4.
- Selective serotonin reuptake inhibitors (SSRIs) may be used to prevent or treat Long COVID, as they increase synaptic serotonin availability, and some studies suggest that low serotonin may drive many Long COVID symptoms across a range of biological systems 5.
- A treatable traits approach, which is a personalized medicine approach, may be applied to Long COVID, by identifying the most prevalent Long COVID treatable traits and then the available evidence for strategies to target these traits 6.
Novel Aspects in Pathogenesis, Diagnosis, and Treatment Protocols
- A unified theory of Long COVID has been proposed, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology 7.
- The theory suggests that viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease, and that innovative diagnostic and therapeutic approaches are needed to address the complex puzzle of Long COVID 7.
- The study hints toward a patient approach and how to prioritize treatment sequences in Long COVID patients in hospitals and clinics, and explains the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with Long COVID 7.