What is the recommended diagnostic evaluation and management for patients with long haul Covid (Coronavirus disease 2019)?

Diagnostic Evaluation and Management of Long COVID

Definition and Diagnostic Criteria

Long COVID should be diagnosed when patients have new, returning, or ongoing symptoms persisting beyond 4 weeks (CDC definition) or 12 weeks (WHO definition) after acute SARS-CoV-2 infection, with symptoms lasting at least 2 months and no other identifiable cause. 1, 2, 3

• A prior positive PCR or antigen test is not required for diagnosis—clinical diagnosis of prior COVID-19 is sufficient 2
• Long COVID is a diagnosis of exclusion after ruling out serious complications and alternative diagnoses 1
• Affects approximately 10-30% of all COVID-19 patients, regardless of initial disease severity 2, 3

Initial Diagnostic Approach: Rule Out Life-Threatening Conditions First

Before diagnosing long COVID, you must systematically exclude:

• Thromboembolic events (pulmonary embolism, deep vein thrombosis) 1
• Myocarditis or pericarditis 1
• Encephalitis or other acute neurological emergencies 1
• Previously overlooked malignancy 1
• Post-intensive care syndrome in critically ill patients (difficult to distinguish from long COVID) 1
• Iatrogenic complications from acute COVID-19 treatment 1
• Unmasking of preexisting conditions (diabetes, thyroid disease, cardiac disease) 1, 2

Structured Clinical Assessment

History Taking

Obtain detailed history focusing on:

• Symptom timeline: When symptoms began relative to acute infection, pattern of fluctuation, relapse-remit nature 2
• Pre-existing conditions: Respiratory disease (23% prevalence), depression/anxiety (34% prevalence) 4
• Acute COVID-19 severity: Hospitalization status, ICU admission, ventilatory support 5
• Functional impact: Ability to perform activities of daily living (34% report difficulties), work status (only 33% return to unrestricted duty) 4

Most Common Presenting Symptoms (by Prevalence at 3-6 Months)

General symptoms:

• Fatigue: 31% (most prevalent, strongest association with severe acute disease) 5, 1
• Chest pain/tightness: 6.4% 5
• Fever: 1.1% 5

Respiratory symptoms:

• Dyspnoea: 25% 5, 1
• Cough: 8.2% 5, 1

Neurological/Cognitive symptoms:

• Anosmia: 15.2% 5, 1
• Dysgeusia: 13.5% 5, 1
• Brain fog/confusion: 17.9% 5
• Depression: 8% 5, 1
• Sleep disorders: 18.2% 5

Musculoskeletal symptoms:

• Myalgia: 11.3% 5, 1
• Joint pain/arthralgia: 9.4% 5, 1

Cardiovascular symptoms:

• Palpitations: 9.7% 5

Laboratory and Diagnostic Testing

Basic Laboratory Panel (For All Symptomatic Patients)

Order the following tests to rule out alternative diagnoses:

• C-reactive protein 5, 1
• Complete blood count 5, 1
• Kidney function tests (creatinine, BUN) 5, 1
• Liver function tests (AST, ALT, bilirubin) 5, 1

Symptom-Specific Testing

For cardiac symptoms (chest pain, palpitations):

• Troponin 5, 1
• CPK-MB 5, 1
• B-type natriuretic peptide (BNP) 5, 1

For suspected thyroiditis:

• Complete thyroid function panel (TSH, free T4, free T3) 5, 1

For diabetes risk factors:

• Fasting glucose 5, 1
• Hemoglobin A1c 5, 1

Important caveat:

• Do NOT order D-dimer in patients without respiratory symptoms 5, 1
• Blood gases have limited benefit even with decreased oxygen saturation 5, 1

Pulmonary Function Testing for Dyspnoea

Indications for PFT

Consider routine pulmonary function testing with diffusion capacity (DLCO) at 3 months for:

• All patients with severe or critical acute COVID-19, regardless of current symptoms 5
• Any patient with persistent dyspnoea at 4-12 weeks 5

Expected Abnormalities by Disease Severity

After critical disease (ICU admission):

• DLCO <80%: Up to 80% at discharge, 50-70% at 3 months, 23-54% at 12 months 5
• Total lung capacity <80%: 39% at 6 months, 29% at 12 months 5

After severe disease (hospitalized, non-ICU):

• DLCO <80%: 30-68% at 3 months, 29% at 6 months 5

After mild-to-moderate disease:

• DLCO <80%: 10-22% still show abnormalities despite normal median values 5

Key finding: The most frequently impaired parameter is DLCO, with restrictive pattern most common 5

Chest Imaging

Chest imaging is NOT recommended for:

• Asymptomatic contacts of COVID-19 patients 5
• Routine diagnostic workup when RT-PCR is available with timely results 5

Chest imaging SHOULD be used when:

• RT-PCR is unavailable or results are delayed 5
• Clinical suspicion of complications (pneumonia, pulmonary embolism, pulmonary fibrosis) 5
• Deciding on hospital admission versus home discharge for mild symptomatic patients 5
• Patient has high-risk comorbidities (diabetes, hypertension, heart disease, obesity, age >60) 5

Risk Factors for Developing Long COVID

Strongest risk factors:

• Female sex: 2-fold increased risk (OR 1.3-5.0) 1
• Severe acute COVID-19: Strongest association with persistent fatigue 1
• Pre-existing mental health conditions: Depression/anxiety present in 34% 4

Quality of Life Assessment

Conduct structured interview to assess:

• Symptom severity using validated scales (e.g., modified Medical Research Council dyspnoea scale for respiratory symptoms) 5
• Impact on activities of daily living 1, 4
• Work capacity and return-to-work status 4
• Overall quality of life (57% report decreased QOL beyond 12 weeks) 1

Referral Criteria

Refer ALL patients with symptoms lasting >12 weeks to systematic medical evaluation for:

• Symptom-based management 1
• Multidisciplinary rehabilitation (physical therapy, occupational therapy, brain rehabilitation as needed) 4
• Consideration of specialized interventions (e.g., stellate ganglion block for dysautonomia symptoms, though evidence is limited to case reports) 6

Consider earlier referral at 4-12 weeks based on:

• Symptom severity 1
• Negative symptom trajectory 1
• Significant functional impairment 4

Common Diagnostic Pitfalls

Avoid these errors:

• Ordering extensive testing when symptoms are self-limited without effective therapy 1
• Using D-dimer inappropriately in non-respiratory presentations 5, 1
• Failing to distinguish post-intensive care syndrome from long COVID in critically ill patients 1
• Missing reactivation of latent viruses (EBV, HHV-6) which may contribute to symptoms 7
• Overlooking gut microbiome disturbances and autoimmunity markers in refractory cases 7

Note: Most patients (75%) were not hospitalized for acute COVID-19, are younger than 65 years, and are more likely female with no significant preexisting comorbidities 4