What are the common post‑influenza complications involving the respiratory mucosa and eyes, and what are the recommended treatments, particularly in children, the elderly, and patients with chronic lung disease, diabetes, or immunosuppression?

Post-Influenza Complications Involving Mucous Membranes

Primary Mucosal Manifestations

Influenza characteristically causes hyperemic mucous membranes around the nose and pharynx, along with injected (red) eyes during the acute phase of infection. 1

Respiratory Mucosa Involvement

• Nasal and pharyngeal hyperemia develops early in infection, typically appearing within 24 hours of symptom onset alongside fever, and represents direct viral inflammation of the upper respiratory mucous membranes 1
• The mucous membranes remain inflamed throughout the acute illness, which typically resolves within 7 days, though some symptoms may persist for weeks 1
• Productive cough with chest tightness occurs in up to 40% of cases and is more common in patients with underlying chronic lung disease, reflecting lower respiratory mucosal involvement 1

Ocular Mucosa Involvement

• Injected eyes (conjunctival hyperemia) are a recognized clinical finding during acute influenza, appearing as part of the toxic appearance in initial stages 1
• Influenza virus can establish productive infection in ocular tissue during the acute phase, with the ocular surface serving as both a site of virus replication and a portal of entry for respiratory infection 2
• Sporadic reports of conjunctivitis following human influenza infection demonstrate the virus's ability to cause disease outside the respiratory tract 2

Post-Influenza Pulmonary Complications

Pneumonia (Most Common Serious Complication)

The incidence of pneumonia complicating influenza ranges from 2% to 38%, occurring more frequently and with greater severity in patients with pre-existing chronic cardiac and respiratory conditions. 1

Primary Viral Pneumonia

• Presents with bilateral diffuse lung infiltrates on chest radiograph 1
• Carries high mortality rate (>40%) 1
• More common in patients with underlying chronic lung disease 1, 3

Secondary Bacterial Pneumonia

• Staphylococcus aureus (including MRSA) is a critical pathogen, identified 2.5 times more frequently during pandemics compared to interpandemic periods, and is associated with higher incidence of lung abscess formation (14% vs 2%) and poorer prognosis (mortality 47% vs 16%) 1, 4
• Streptococcus pneumoniae remains the predominant pathogen in many series (48% in 1968 pandemic) 1
• Non-typeable Haemophilus influenzae accounts for approximately 11% of cases 1
• Up to 75% of influenza patients who develop pneumonia test positive for bacterial coinfection 1

Mixed Viral-Bacterial Pneumonia

• Demonstrates lobar consolidation superimposed on bilateral diffuse lung infiltrates 1
• Carries high mortality rate (>40%), similar to primary viral pneumonia 1

High-Risk Populations Requiring Aggressive Management

Children

Children at highest risk include those with chronic respiratory disease (asthma requiring continuous/repeated steroids, cystic fibrosis, bronchiectasis), congenital heart disease, immunodeficiency, diabetes, and neurological diseases with muscle weakness. 1

• Children under 1 year of age are at particularly high risk for complications 4
• Oseltamivir dosing for children over 1 year: <15 kg receive 30 mg every 12 hours; 15-23 kg receive 45 mg every 12 hours; >24 kg receive 75 mg every 12 hours 1
• Antibiotic coverage for pneumonia in children: co-amoxiclav (age-based dosing from 2.5 ml/kg for <1 year to 5 ml of 250/62 suspension for >6 years, three times daily) or clarithromycin if allergic 1

Elderly Patients (≥65 Years)

All patients aged 65 years or older are automatically classified as high-risk regardless of other factors and warrant immediate antiviral therapy without waiting for laboratory confirmation. 1, 5

• Elderly patients may not mount adequate febrile responses and can present with atypical symptoms including lassitude and confusion without prominent fever 5
• CURB-65 score should be calculated immediately (1 point each for: Confusion, Urea >7 mmol/L, Respiratory rate ≥30/min, Blood pressure SBP <90 or DBP ≤60 mmHg, Age ≥65 years) 1, 5
• Score 0-1: consider home treatment; Score 2: short inpatient stay or hospital-supervised outpatient management; Score ≥3: hospitalization required 1, 5
• For creatinine clearance <30 mL/min, reduce oseltamivir dose to 75 mg once daily 5

Patients with Chronic Lung Disease

Patients with COPD, asthma, bronchiectasis, cystic fibrosis, and interstitial lung disease experience more frequent and severe pneumonia complications, with productive cough, chest tightness, and substernal soreness being more common. 1

• Continue inhaled corticosteroids for asthma/COPD management during influenza 6
• May require systemic steroids specifically for asthma/COPD exacerbation, but never add corticosteroids for influenza treatment itself as they increase mortality (OR 3.06,95% CI 1.58-5.92) and risk of secondary bacterial infections 6, 7, 8
• For COPD exacerbation, add systemic corticosteroids, short-acting bronchodilators, and antibiotics to oseltamivir 6

Patients with Diabetes

Diabetes increases the odds of ICU admission for influenza by more than 4-fold (OR 4.29), with higher rates of hospitalization, pneumonia, and influenza-related deaths. 1

• Chronic hyperglycemia decreases immune cell recruitment, neutrophil degranulation, complement activation, and phagocytosis, collectively limiting immune response to influenza 1
• Elevated glucose levels increase influenza virus replication in pulmonary epithelial cells and trigger complications including heart and kidney disease 1
• Influenza infection can exacerbate diabetic ketoacidosis and is associated with a 75% increase in frequency of abnormal glucose levels 1
• Decompensated diabetes increases risk of influenza complications, and influenza can lead to decompensated diabetes 1

Immunosuppressed Patients

Patients on immunosuppressive doses of steroids (≥20 mg/day prednisolone for >1 month, or ≥1 mg/kg/day in children <20 kg), those with HIV/AIDS, malignancy, asplenia, or undergoing chemotherapy are at high risk for severe and prolonged influenza. 1, 6

• Acute respiratory failure in immunosuppressed patients admitted to ICU carries very high mortality risk 1
• Pneumonitis is common and can be fatal in up to 7% of transplant recipients 1
• Patients with hematologic malignancies on chemotherapy have increased risk of pneumonia and mortality up to 43% 1
• Continue chronic steroids at lowest effective dose while prioritizing immediate antiviral therapy—never abruptly stop due to adrenal insufficiency risk 6, 7

Recommended Treatment Algorithm

Immediate Antiviral Therapy

Oseltamivir 75 mg orally twice daily for 5 days should be initiated immediately in all hospitalized patients, patients with severe or progressive illness, and all high-risk patients, without waiting for laboratory confirmation. 6, 5, 8

• Treatment is most effective when started within 48 hours of symptom onset, but hospitalized and high-risk patients may benefit even when started beyond 48 hours 6, 5, 8
• Standard-dose oseltamivir is well absorbed in critically ill patients 8

Antibiotic Coverage for Pneumonia

All patients with influenza pneumonia should receive antibiotics to cover bacterial coinfection or secondary infection, as up to 75% test positive for bacterial coinfection. 1, 7

Non-Severe Pneumonia (CURB-65 0-2)

• Oral co-amoxiclav (adults: 250/125 mg three times daily; children: age-based dosing) 1, 7
• Alternative: doxycycline 100 mg once daily for patients >12 years 1
• Alternative: clarithromycin (age-based dosing for children, 250 mg twice daily for adults >10 years) 1

Severe Pneumonia (Bilateral lung shadows or CURB-65 3-5)

• Intravenous broad-spectrum β-lactamase stable antibiotic (co-amoxiclav 30 mg/kg three times daily or cefuroxime 20-30 mg/kg three times daily) PLUS macrolide (clarithromycin 5-7 mg/kg twice daily IV) 1, 7
• Must cover Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, and Haemophilus influenzae 1, 7, 4

Supportive Care

• Oxygen therapy to maintain pO2 >8 kPa or SaO2 >92% 1
• Intravenous fluids as needed 1
• Acetaminophen or ibuprofen for fever, headache, and myalgia (avoid aspirin in children due to Reye's syndrome risk) 1, 5

Critical Pitfalls to Avoid

• Never add corticosteroids for influenza pneumonia treatment—they increase mortality (OR 3.06), delay viral clearance, and increase secondary bacterial infections 6, 7, 8
• Never withhold oseltamivir based solely on time from symptom onset in high-risk or hospitalized patients, as they may benefit even with delayed presentation 6, 5
• Never abruptly stop chronic steroids in patients who develop influenza—taper gradually while treating with antivirals to avoid adrenal insufficiency 6, 7
• Never rule out influenza based on absence of fever in elderly patients, as they frequently present with atypical symptoms 5
• Never prescribe antibiotics prophylactically without evidence of bacterial infection, as this promotes resistance without proven benefit 5
• Never use antigen detection assays alone in critically ill patients due to lower sensitivity—always confirm with molecular testing 8