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

Diagnostic Approach for Long COVID

Long COVID should be assessed in any patient with persisting or new symptoms that last more than 12 weeks after acute COVID-19 infection, with assessment considered on a case-by-case basis for symptoms between 4-12 weeks after infection. 1

Definition and Classification

Long COVID is diagnosed when symptoms persist beyond 12 weeks after SARS-CoV-2 infection and can be categorized as:

• Post-acute COVID: Symptoms 4-12 weeks after infection
• Persistent long COVID: Symptoms >12 weeks after infection 1

These can be further classified based on diagnostic certainty:

• Confirmed: Positive lab results for COVID-19
• Probable: Negative lab results but suggestive epidemiology
• Possible: Negative lab results and negative epidemiology 1

Diagnostic Algorithm

Step 1: Rule Out Other Conditions

• Long COVID is a diagnosis of exclusion 1
• First, rule out:
  • Previously overlooked conditions (e.g., malignancy)
  • Complications of acute COVID-19 (e.g., thromboembolic events, myocarditis, encephalitis)
  • Iatrogenic causes related to the acute episode 1

Step 2: Initial Laboratory Assessment

• Complete blood count
• Kidney function tests
• Liver function tests
• C-reactive protein (note: normal results don't rule out long COVID)
• Thyroid function tests (TSH, free T3, free T4, anti-thyroid antibodies) - especially important for those with severe fatigue 1, 2

Step 3: Symptom-Specific Assessment

For respiratory symptoms:

• Oxygen saturation
• Consider pulmonary function testing with diffusion capacity 2
• Consider chest imaging for persistent symptoms

For cardiac symptoms:

• Troponin
• B-type natriuretic peptide (BNP)
• Consider ECG (look for new fragmentation of QRS complex) 1

For neurological symptoms:

• Consider cognitive assessment tools
• For dizziness/POTS: orthostatic vital signs or tilt table test 1, 2

For gastrointestinal symptoms:

• Consider specific testing based on symptoms 2

Common Long COVID Symptoms to Evaluate

The most prevalent symptoms to assess for include:

• Fatigue (31-58% of patients)
• Dyspnea (25-37%)
• Chest pain (6-17%)
• Cognitive dysfunction ("brain fog")
• Anosmia/dysgeusia (13-21%)
• Sleep disorders
• Headache
• Depression
• Joint pain 1, 2

Special Considerations

For Women

• Assess for menstrual cycle changes (reported in 10-30% of women post-COVID)
• Note timing of symptoms in relation to menstrual cycle, as pre-menstrual periods may trigger symptom flares 2

For Fatigue Assessment

If thyroid function is normal, evaluate for:

• Dysautonomia/POTS (present in up to 67% of long COVID patients)
• ME/CFS patterns
• Deconditioning (common even after mild infection) 2

Emerging Diagnostic Tools

While not yet widely available, research is developing promising diagnostic tools:

• Imaging to detect microclots
• Corneal microscopy to identify small fiber neuropathy
• Hyperpolarized MRI to detect pulmonary gas exchange abnormalities 1

Important Clinical Pitfalls to Avoid

1. Don't dismiss symptoms as psychological - Long COVID is a recognized medical condition with physiological basis 2

2. Don't overlook thyroid dysfunction - COVID-19 can trigger thyroid abnormalities that persist during long COVID 2

3. Don't rely solely on standard tests - Many patients with long COVID have normal standard test results despite significant symptoms 1

4. Don't miss post-exertional malaise - Activity that worsens symptoms 24-48 hours later is a hallmark of ME/CFS patterns in long COVID 3

5. Don't forget to validate patient experiences - Many patients report having their symptoms dismissed by healthcare providers 3

Long COVID remains a clinical diagnosis that requires thorough evaluation and exclusion of alternative explanations. The diagnostic approach should be comprehensive but targeted to the specific symptom clusters experienced by each patient.