CRP in Influenza: Clinical Utility and Interpretation
C-reactive protein is typically only mildly elevated in uncomplicated influenza (usually <50 mg/L), but markedly elevated CRP levels (>80-100 mg/L) strongly suggest bacterial superinfection rather than viral infection alone. 1, 2
Primary Guideline Recommendations
CRP is unlikely to be helpful in uncomplicated influenza except where superimposed bacterial infection is suspected. 1 The British Infection Society and British Thoracic Society explicitly state that CRP measurement should be obtained in hospitalized patients primarily when secondary bacterial infection is suspected, not for routine influenza diagnosis. 1
CRP Levels by Infection Type
Uncomplicated Viral Influenza
- CRP values in uncomplicated influenza typically range from 7-25 mg/L, with peak levels occurring on days 2-4 of illness 3, 2
- Among patients with confirmed influenza A or B infection, mean CRP levels are approximately 25.7 mg/L 2
- Moderately elevated CRP (10-60 mg/L) is common in viral upper respiratory infections and cannot support bacterial diagnosis when illness duration is less than 7 days 3
Severe Influenza Without Bacterial Coinfection
- Patients with severe H1N1 influenza have significantly higher CRP levels than those with non-severe disease 4
- CRP levels correlate with symptom severity in acute influenza A infection (correlation coefficient r = 0.65, P=0.00056) 5
- Influenza-related pneumonia and hospitalized patients show 1.4- to 2.5-fold higher CRP levels compared to uncomplicated cases 4
Bacterial Superinfection
- CRP >80 mg/L has 100% specificity for bacterial infection in patients presenting with influenza-like illness 2
- CRP <20 mg/L has 100% sensitivity for ruling out bacterial infection 2
- Mean CRP in bacterial infections complicating influenza is approximately 136 mg/L, significantly higher than viral infection alone (P <0.001) 2
- Patients with complicated influenza (bacterial superinfection) have significantly more elevated CRP than uncomplicated influenza 6
Clinical Algorithm for CRP Interpretation
When to Order CRP
- Obtain CRP in hospitalized patients with influenza-like illness as part of standard blood work 7
- Specifically order CRP when bacterial superinfection is suspected based on: 1
- Failure to improve after 3-5 days
- Secondary fever after initial improvement
- New or worsening respiratory symptoms
- Hemodynamic instability or severe pneumonia
Interpretation Thresholds
- CRP <20 mg/L: Bacterial infection highly unlikely; continue supportive care for viral illness 2
- CRP 20-80 mg/L: Indeterminate zone; consider clinical context, duration of illness, and trend over time 3, 2
- CRP >80 mg/L: Bacterial superinfection highly likely; initiate empirical antibiotics targeting Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae 1, 2
Critical Pitfalls to Avoid
- Do not use CRP alone to diagnose bacterial infection in the first 7 days of illness, as moderately elevated values (10-60 mg/L) are common in uncomplicated viral infections 3
- Do not withhold antibiotics in severely ill patients while awaiting CRP results; clinical judgment and severity assessment (CURB-65 score ≥3) should guide immediate management 1
- Do not ignore persistently elevated CRP (>10 mg/L) beyond 7 days of illness, as this may indicate bacterial superinfection even if initial presentation was viral 3
- Remember that the diagnostic value of CRP in lower respiratory tract infections remains controversial, and it should be used in conjunction with clinical assessment, imaging, and microbiological testing 1
Additional Laboratory Context
When CRP is obtained, also measure: 1, 7
- Full blood count (leukocytosis with left shift suggests bacterial coinfection; lymphopenia may indicate severe viral infection)
- Urea and electrolytes (assess for complications)
- Creatine kinase if severe myalgia is present (influenza-associated myositis can cause marked elevation) 8
- Blood cultures if bacterial infection is suspected 7