What is the management approach for long COVID (Coronavirus disease 2019)?

Management of Long COVID

Long COVID requires a structured, symptom-based management approach centered on energy conservation, multidisciplinary rehabilitation, and symptomatic treatment, as there are currently no evidence-based pharmacological interventions proven effective for this condition. 1

Definition and Prevalence

Long COVID affects 22-40% of convalescent patients who experience persistent symptoms beyond the acute infection phase 1. The condition is defined by temporal categories 1:

• Ongoing symptomatic COVID-19: Symptoms present from 4-12 weeks after acute infection 1
• Post-COVID-19 syndrome: Symptoms persisting beyond 12 weeks that are not explained by alternative diagnoses 1

Critical caveat: The likelihood of developing long COVID is not related to the severity of acute infection, meaning even mild cases can develop debilitating long-term symptoms 1.

Most Common Symptoms

The predominant symptoms requiring management are 1:

• Fatigue (most common)
• Dyspnea/breathlessness
• Cognitive impairment ("brain fog")
• Pain syndromes (chest pain, headache, myalgia)

Important: Symptoms may be singular, multiple, constant, transient, fluctuating, or change in nature over time 1.

Initial Assessment and Diagnostic Workup

Essential Baseline Evaluation

Offer chest radiograph by 12 weeks after acute COVID-19 if the person has continuing respiratory symptoms and has not had one already 1.

Conduct screening for 2:

• Physical deconditioning and functional limitations
• Respiratory impairment (pulmonary diffusion capacity, oxygen saturation on exertion)
• Cognitive dysfunction (attention, memory, executive function)
• Mental health disorders (anxiety, depression, PTSD)
• Dysautonomia symptoms (orthostatic intolerance, tachycardia)

Critical point: A positive COVID-19 test during acute infection is not required to diagnose long COVID 2.

Management Framework: Four-Step Approach

Step 1: Energy Conservation and Prevention of Post-Exertional Malaise (PEM)

This is the foundational step and must be implemented first 3, 2.

• Educate patients about PEM/PESE (post-exertional symptom exacerbation), which is a cardinal feature where symptoms worsen 12-48 hours after physical or cognitive exertion 3, 2
• Implement pacing strategies: Patients must stay within their "energy envelope" and avoid pushing through fatigue 3, 2
• Breathing control techniques: High side lying, forward lean sitting, pursed lip breathing, and square box breathing 1
• Activity regulation: Appropriate walking pace to reduce breathlessness and prevent oxygen desaturation 1

Major pitfall: Overly intense physical activity can trigger PEM/PESE and worsen muscle damage—standard exercise prescriptions used for deconditioning are contraindicated until energy tolerance improves 2.

Step 2: Multidisciplinary Rehabilitation

All severe COVID-19 patients should receive education and support for self-management of breathlessness and resumption of activities 1.

Rehabilitation should address 4, 2:

• Pulmonary rehabilitation for respiratory symptoms (dyspnea, reduced exercise tolerance)
• Physical therapy focusing on strengthening rather than endurance to prevent deconditioning 5
• Occupational therapy for cognitive rehabilitation and return-to-work planning
• Vestibular rehabilitation for patients with vertigo or balance issues 6
• Speech and language pathology for swallowing difficulties or communication impairments

Delivery method: Group-based programs combining exercise, breathing techniques, education, and psychological support have shown promise 4, 5. Telerehabilitation is safe, feasible, and eliminates healthcare access barriers 4.

Step 3: Symptomatic Management

No specific pharmacological interventions have proven efficacy in high-quality studies for long COVID 1. Therefore, medication use follows standard practice for symptom management 2:

For Fatigue

• Rule out treatable causes (anemia, thyroid dysfunction, sleep disorders)
• Consider group cognitive behavioral therapy (CBT) approaches focused on self-management and functional planning 5
• Avoid stimulants that may worsen PEM/PESE 2

For Cognitive Impairment

• Cognitive rehabilitation strategies
• Workplace accommodations (reduced hours, flexible scheduling, quiet workspace)
• Caution: Medications for attention (e.g., stimulants) may improve cognition but worsen PEM/PESE 2

For Dysautonomia/POTS

• Increased fluid and salt intake
• Compression garments
• Gradual reconditioning within energy limits

For Gastrointestinal Symptoms

• Traditional Chinese Medicine approaches using herbs with "tonifying spleen and appetizing" effects may improve abdominal fullness, anorexia, nausea, and diarrhea 1

For Mental Health

• Standard treatment for anxiety and depression
• Validation of patient experience is essential, as many have had symptoms dismissed 2

Important consideration: Prioritize shared decision-making and cautious medication use, as some treatments may improve certain symptoms while worsening others 2.

Step 4: Experimental Targeted Therapies

Evidence is insufficient to recommend for or against any specific experimental intervention 1.

Theoretical treatments mentioned in literature but lacking clinical evidence include 1:

• Luteolin (flavonoid for neuroinflammation)
• Cannabidiol/cannabivarine (for CNS protein downregulation)
• Methylene blue (for neurocognitive impairment)
• Clomipramine (tricyclic antidepressant for mental complications)

These should only be considered on an individual basis following thorough risk-benefit discussion 3.

Return to Work and Disability Considerations

Long COVID is recognized as a potential disability under the Americans with Disabilities Act 2.

Workplace accommodations to recommend 2:

• Flexible scheduling and reduced hours
• Work-from-home options
• Frequent rest breaks
• Modified job duties to reduce physical/cognitive demands
• Quiet workspace for concentration

If work significantly worsens symptoms or impedes recovery, applying for disability may be warranted 2.

Follow-Up and Monitoring

• Regular assessment of symptom progression and functional status 6
• Monitor for new or worsening symptoms, particularly thromboembolic events or neurological complications 6
• Consider a care coordinator to ensure continuity across multiple specialists 6
• Screen all patients before hospital discharge for rehabilitation needs to facilitate timely referral 1

Key Limitations in Current Evidence

Major gaps 1:

• No objective diagnostic criteria or consensus investigation algorithm
• No standardized definition across studies
• Lack of controlled trials for interventions
• Most studies are retrospective and include only symptomatic patients (selection bias)
• Pathophysiology remains poorly understood

The evidence base consists primarily of expert opinion rather than high-quality trials 1, necessitating a cautious, symptom-focused approach prioritizing patient safety and quality of life.