How to manage patients with symptoms of long Covid and a negative C (C reactive protein) result?

Management of Long COVID Patients with Negative C-Reactive Protein Results

Patients with symptoms of long COVID should still receive appropriate clinical management and support even with negative C-reactive protein results, as long COVID is primarily a clinical diagnosis that does not require positive inflammatory markers. 1, 2

Diagnostic Approach

Long COVID is fundamentally a diagnosis of exclusion that should be considered in patients with persistent symptoms following COVID-19 infection, regardless of laboratory findings. The diagnostic process should follow this algorithm:

1. Confirm timing of symptoms:

   • 4-12 weeks after infection: Classified as "post-acute COVID"

   • 12 weeks after infection: Classified as "persistent long COVID" 1

2. Categorize based on laboratory evidence:

   • With negative CRP and other laboratory results but suggestive epidemiology: "Probable long COVID"
   • With negative CRP and laboratory results and negative epidemiology: "Possible long COVID" 1

3. Rule out alternative diagnoses through targeted investigations based on presenting symptoms 1, 2

Clinical Assessment

The most common long COVID symptoms to evaluate include:

• Fatigue (31-58% of patients)
• Dyspnea (25-37% of patients)
• Chest pain (6-17% of patients)
• Cognitive dysfunction
• Sleep disorders
• Anosmia/dysgeusia (13-21% of patients) 1

Important Considerations with Negative CRP

• A negative CRP does not exclude long COVID diagnosis, as many patients with established long COVID have normal inflammatory markers 2
• CRP is primarily useful in acute COVID-19 for predicting disease severity and outcomes, not for diagnosing long COVID 3, 4, 5, 6
• The absence of elevated CRP may actually be expected in many long COVID patients, as the acute inflammatory phase has typically resolved 1, 2

Management Algorithm

1. Initial laboratory workup (despite negative CRP):

   • Complete blood count
   • Kidney and liver function tests
   • Thyroid function tests
   • Consider cardiac markers (troponin, BNP) if cardiac symptoms present 1, 2

2. Symptom-specific assessments:

   • For dyspnea: Consider pulmonary function testing, especially diffusion capacity 1, 2
   • For cardiac symptoms: Consider ECG, echocardiogram 2
   • For cognitive symptoms: Consider cognitive assessment tools 2
   • For orthostatic symptoms: Perform 3-minute active stand test 2

3. Symptom-based management:

   • Breathlessness: Controlled breathing techniques, positioning, relaxation techniques 2
   • Persistent cough: Consider honey and lemon in warm water; codeine linctus if distressing 2
   • Fatigue: Activity pacing, energy conservation strategies 2
   • Sleep disturbances: Sleep hygiene optimization 2
   • Cognitive issues: Memory aids, written lists, breaking tasks into smaller steps 2

4. Rehabilitation approach:

   • Gradual, phased return to activities based on symptom tolerance
   • Consider referral to specialized long COVID rehabilitation services if available 2

Key Pitfalls to Avoid

• Do not dismiss symptoms due to negative CRP or other normal test results - long COVID is primarily a clinical diagnosis 2
• Avoid overreliance on CRP as a diagnostic marker for long COVID - while useful in acute COVID-19, it has limited utility in long COVID diagnosis 3, 4, 7
• Prevent diagnostic delay by recognizing that long COVID can present with normal inflammatory markers 2
• Don't expect rapid recovery - symptoms often fluctuate and may persist for months 2
• Avoid polypharmacy without clear indications - focus on symptom management and supportive care 2

Follow-up Recommendations

• Schedule regular follow-up visits to assess symptom progression
• Adjust management plan as symptoms evolve
• Consider specialized referrals for persistent or severe symptoms 1, 2

By following this approach, clinicians can provide appropriate care for patients with long COVID symptoms despite negative CRP results, focusing on symptom management, functional improvement, and quality of life.