What diseases and complications are associated with influenza infection?

Diseases and Complications Caused by Influenza Infection

Influenza causes a spectrum of diseases ranging from uncomplicated respiratory illness to life-threatening complications including primary viral pneumonia, secondary bacterial pneumonia, myocarditis, encephalopathy, and exacerbation of chronic medical conditions, with mortality risk highest among adults >65 years, young children, pregnant women, and immunocompromised individuals. 1

Primary Respiratory Diseases

Uncomplicated Influenza

• Characterized by abrupt onset of fever (typically 38-41°C), myalgia, headache, severe malaise, nonproductive cough, sore throat, and rhinitis 1
• Fever peaks within 24 hours and typically lasts 3 days (range 1-5 days) 1
• Illness usually resolves in 7 days, though cough and malaise can persist for weeks 1
• In children, otitis media, nausea, and vomiting are commonly reported 1
• Young children may present atypically with high fevers mimicking bacterial sepsis 1

Primary Viral Pneumonia

• The most common cause of hospitalization during the 2009 H1N1 pandemic, presenting as diffuse viral pneumonitis that can lead to shock and respiratory failure 1
• Patients typically become breathless within the first 48 hours of fever onset 1
• Initially dry cough may become productive of blood-stained sputum, with cyanosis, tachypnea, bilateral crepitations and wheeze 1
• Occurs in more than 70% of ICU influenza patients 2
• More than 50% of severe cases develop acute respiratory distress syndrome (ARDS) 2

Secondary Bacterial Pneumonia

• Occurs in 20-38% of patients who died or required ICU admission during the 2009 H1N1 pandemic 1
• Most commonly caused by Staphylococcus aureus, Streptococcus pneumoniae, and S. pyogenes 1
• Up to 75% of influenza patients who develop pneumonia test positive for bacterial coinfection 1
• Generally develops during early convalescence (4-5 days after onset) 3

Cardiovascular Complications

Cardiac Manifestations

• Myocarditis occurs rarely but is associated with mortality 1
• Pericarditis is a rare complication 1
• ECG abnormalities are common, showing non-specific T wave and rhythm changes, ST segment deviation, mostly not associated with cardiac symptoms 1
• Late-onset cardiovascular complications are associated with mortality 2
• Exacerbation of underlying cardiac disease is a major contributor to morbidity and mortality 1

Neurological Complications

Central Nervous System Involvement

• Encephalopathy/encephalitis occurs rarely, typically within the first week of illness, and is more common in children and in Japan 1
• Transverse myelitis is very rare 1
• Guillain-Barré syndrome is very rare 1
• Seizures are the most common neurologic complication, occurring as febrile seizures or exacerbations in patients with epilepsy 4
• One study reported more neurologic complications associated with 2009 H1N1 virus infection among children compared with seasonal influenza 1

Musculoskeletal Complications

• Myositis occurs uncommonly during early convalescence 1
• Myoglobinuria and renal failure are rare 1
• Reye's syndrome has been associated with influenza infection 1

Exacerbation of Chronic Conditions

High-Risk Populations

• Exacerbation of asthma, chronic obstructive pulmonary disease (COPD), or cardiac disease is a major contributor to morbidity and mortality 1
• One or more underlying comorbidities were present in 50-80% of adults and children requiring hospitalization 1
• Influenza can exacerbate diabetic ketoacidosis and cause a 75% increase in frequency of abnormal glucose levels among type 2 diabetes patients 1
• Hyperglycemia decreases immune cell recruitment, neutrophil degranulation, complement activation, and phagocytosis, limiting immune response to influenza 1

Pediatric-Specific Complications

Children Under 5 Years

• Hospitalization rates in children aged 0-4 years range from 100/100,000 for those without high-risk conditions to 500/100,000 for those with high-risk conditions 1
• Infants aged <6 months have the highest hospitalization rates, comparable to those >65 years 1
• Among hospitalized children, 4-11% require ICU treatment and 3% require mechanical ventilation 1
• Children can be infectious for >10 days and may shed virus for <6 days before illness onset 1
• Febrile seizures occur in <20% of children hospitalized with influenza 1

High-Risk Groups for Severe Disease

Mortality and Hospitalization Risk

• Adults >65 years account for >90% of deaths attributed to pneumonia and influenza 1
• Pregnant and postpartum women (within 2 weeks of delivery) are at increased risk, accounting for 6-10% of patients who required hospitalization or died in some case series 1
• Severely immunocompromised persons can shed virus for weeks or months 1
• Acute respiratory failure in immunosuppressed patients admitted to ICU has been linked to very high mortality risk 1

Other Complications

• Otitis media is common, particularly in children 1
• Toxic shock syndrome is rare 1
• Parotitis is very rare 1
• Pneumonitis is common in immunocompromised populations and can be fatal in up to 7% of patients 1

Critical Clinical Considerations

Respiratory illnesses caused by influenza are difficult to distinguish from other respiratory pathogens based on symptoms alone, with clinical definitions showing sensitivity of only 63-78% and specificity of 55-71% compared to viral culture. 1 The positive predictive value of fever and cough together varies from 79-88% in adults during confirmed influenza circulation, but only 64-71% in children aged <5 years 1. Laboratory confirmation is recommended for hospitalized patients and high-risk individuals where results would influence management decisions 1.