In a patient with influenza who has metamyelocytes on a peripheral blood smear, what does this finding indicate and how should it be evaluated and managed?

Metamyelocytes in Influenza: Clinical Significance and Management

Metamyelocytes on peripheral blood smear in an influenza patient indicate a "left shift" reflecting bone marrow stress response and should prompt immediate evaluation for severe viral pneumonia or bacterial superinfection, both of which carry significant mortality risk.

What This Finding Indicates

Metamyelocytes represent immature granulocytes released prematurely from bone marrow in response to severe infection. 1 In the context of influenza, this left shift has three critical implications:

• Primary viral pneumonia with severe systemic inflammation – The British Infection Society guidelines explicitly state that leukocytosis with left shift may occur in primary viral pneumonia, indicating severe disease 1
• Mixed viral-bacterial pneumonia – The same left shift pattern occurs when bacterial coinfection complicates influenza 1
• Secondary bacterial pneumonia – Metamyelocytes appearing 4-5 days after initial influenza symptoms strongly suggest bacterial superinfection, most commonly with Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae 1, 2

Immediate Clinical Evaluation Required

Assess severity using CURB-65 score immediately: 1, 3

• Confusion (Mental Test Score <8 or new disorientation)
• Urea >7 mmol/L
• Respiratory rate >30/min
• Blood pressure (SBP <90 or DBP <60 mmHg)
• Age >65 years

A CURB-65 score ≥3 mandates hospital management as severe pneumonia regardless of other findings. 1, 3

Essential Diagnostic Workup

Obtain chest radiograph immediately – This is mandatory for all hospitalized influenza patients to identify bilateral infiltrates (primary viral pneumonia), cavitation, or pleural effusions (bacterial superinfection). 1, 3 New bilateral lung shadowing indicates severe disease regardless of CURB-65 score. 1

Complete the following blood tests: 1, 3

• Full blood count with differential (already done, showing metamyelocytes)
• Urea, creatinine, and electrolytes
• Liver function tests
• C-reactive protein (CRP) – Critical for distinguishing bacterial superinfection

CRP interpretation is decisive: 4

• CRP >80-100 mg/L strongly indicates bacterial superinfection requiring immediate antibiotics
• CRP <50 mg/L suggests uncomplicated viral infection
• The diagnostic value of CRP in lower respiratory infections remains controversial, but it aids diagnosis when bacterial infection is suspected 1, 4

Obtain microbiological samples before antibiotic administration: 1, 3

• Blood cultures (two sets)
• Sputum for Gram stain and culture
• Respiratory viral testing to confirm influenza

Management Algorithm

For CURB-65 ≥3 OR bilateral infiltrates OR CRP >80 mg/L:

• Do not delay antibiotics while awaiting results 4
• Initiate empirical antibiotics covering S. pneumoniae, S. aureus, and H. influenzae 1, 4
• Consider ICU admission for respiratory support 1, 3

For CURB-65 <3 AND unilateral infiltrate AND CRP <80 mg/L:

• Close monitoring with repeat assessment in 24-48 hours 1
• Consider short inpatient stay if CURB-65 = 2 1

Antiviral therapy considerations:

• Initiate neuraminidase inhibitors within 48 hours of symptom onset if not already started 3
• Continue even if bacterial superinfection suspected 3

Critical Pitfalls to Avoid

Do not assume metamyelocytes always indicate bacterial infection – Primary severe viral pneumonia (including H5N1) can produce leukocytosis with left shift without bacterial coinfection. 1, 2 The distinction requires integration of clinical timeline, imaging, and CRP levels.

Do not wait for culture results to start antibiotics in severe cases – Bacterial superinfection carries high mortality; empirical therapy must begin immediately when CURB-65 ≥3 or CRP >80 mg/L. 1, 4

Do not overlook the timing of symptom evolution – Secondary bacterial pneumonia typically develops 4-5 days after initial influenza symptoms, often after apparent improvement. 2 Metamyelocytes appearing in this timeframe strongly suggest bacterial superinfection.

Remember that profound leukopenia (not leukocytosis) predicts worse outcomes in severe influenza – While metamyelocytes indicate left shift, their presence with normal or elevated total WBC is less ominous than profound leukopenia and lymphopenia seen in fatal H5N1 cases. 2

Follow-Up

Repeat chest radiograph at 6 weeks if respiratory symptoms persist after hospital discharge or outpatient management. 1, 3