Introduction:
Influenza, commonly seen as a respiratory infection with significant respiratory mortality, also presents broader consequences. These include cardiovascular events, worsening chronic conditions, susceptibility to secondary bacterial infections, functional decline, and adverse pregnancy outcomes. These factors contribute to an increased risk of hospitalization and death. While measuring these impacts is methodically challenging, evolving epidemiological and interventional study designs aim to assess them better. Recognizing these broader consequences is crucial for understanding the complete burden of influenza across diverse subpopulations and evaluating preventive measures.
What Is Influenza?
Influenza, an acute viral respiratory disease causing annual epidemics and occasional pandemics, easily spreads through aerosolized droplets and contaminated surfaces. Transmission is prominent in the winter in temperate regions and year-round in crowded places like schools and public transport. Symptoms include fever, cough, headache, and muscle pain, with severe cases affecting older adults, infants, pregnant women, overweight individuals, and those with chronic conditions.
Influenza viruses evolve, occasionally leading to pandemics, but public health measures, vaccines, and treatments have mitigated their impact. Despite causing yearly epidemics, global vaccination rates remain below WHO (World Health Organization) recommendations. The global burden of disease study estimates millions of influenza-related lower respiratory tract infections and deaths annually.
Individuals with chronic medical conditions face a disproportionate impact from influenza, constituting up to 80 percent of adult hospital admissions and around 50 percent of children with laboratory-confirmed influenza.
At-risk individuals are more prone to severe influenza and complications due to compromised immune responses and the exacerbation of underlying conditions, leading to increased hospitalization and mortality risks. Specific populations, especially those with chronic heart or respiratory conditions, face the highest risk, which escalates with age.
Pregnant women, another high-risk group, are particularly vulnerable to severe illness, complications, and death from influenza. Beyond maternal consequences, influenza can result in complications such as stillbirth, pre-term delivery, and reduced birth weight.
Notably, controlled trials in developing countries demonstrated that influenza vaccination during pregnancy significantly reduced confirmed influenza cases in mothers and children and respiratory diseases in both groups. Consequently, the WHO recommends prioritizing pregnant women in seasonal influenza immunization programs.
What Are the Complications Associated With Influenza Beyond Respiratory Illness?
Cardiovascular Diseases:
Time-series analyses have shown associations between seasonal influenza and cardiovascular events, with increased winter mortality aligning with peaks in influenza circulation, particularly affecting older adults. Mechanistically, influenza infections can directly impact the cardiovascular system, leading to conditions such as myocardial infarction, exacerbated by systemic effects like inflammation and prothrombotic changes.
Population-level studies have highlighted influenza’s impact on cardiovascular events, with a notable proportion of hospital admissions attributed to influenza during the peak transmission season. Self-controlled case-series studies confirm elevated risks of heart attacks and strokes following influenza infections. Furthermore, influenza vaccination has shown promise in reducing cardiovascular complications, with studies indicating lower risks of all-cause and cardiovascular death in vaccinated individuals.
Chronic Respiratory Conditions:
Due to the considerable burden of influenza on individuals with chronic respiratory conditions, many national immunization advisory groups prioritize annual vaccinations for those with pulmonary disorders and chronic lung diseases. Influenza virus infections in the lungs can precipitate asthma attacks and exacerbate symptoms, even in those with well-controlled asthma.
Influenza and other respiratory viruses frequently exacerbate chronic obstructive pulmonary disease (COPD). Studies have shown a higher presence of the influenza A virus in respiratory specimens from COPD patients hospitalized for exacerbations than in stable COPD patients. Additionally, influenza is linked to increased hospital admissions among older adults.
Diabetes:
Individuals with type 1 and type 2 diabetes are at higher risk of developing severe and potentially fatal complications from influenza. This association was first noted and confirmed during the H1N1 pandemic.
Research indicates that diabetes is associated with increased risks of hospitalization and death from influenza. Patients with diabetes were found to have a fourfold higher likelihood of ICU admission compared to those without diabetes. Additionally, influenza infections can exacerbate diabetic ketoacidosis, leading to further complications. Hyperglycemia in diabetes is thought to contribute to these complications by impairing immune responses and facilitating influenza virus replication in the lungs.
Recognizing the heightened susceptibility of individuals with diabetes to severe influenza infections, the WHO and many national immunization advisory groups recommend prioritizing vaccination for this group to mitigate risks and complications.
Neurological Complications:
In rare cases, influenza virus infection can lead to neurologic complications such as febrile seizures, influenza-associated encephalitis or encephalopathy, Guillain-Barre syndrome, and exacerbations in individuals with epilepsy. While the exact causes of these complications remain unclear, molecular mimicry between viral antigens and self-antigens has been proposed as a potential mechanism. The severity of these rare events varies, and diagnostic tests like electroencephalograms and cerebrospinal fluid studies often struggle to predict long-term outcomes reliably. Neurologic complications of influenza are more commonly reported in children, with some, like encephalitis, potentially having a genetic predisposition, as seen in certain populations.
An association has been suggested between the influenza vaccine and Guillain-Barre syndrome, though the risk is significantly lower than influenza virus infection. The benefits of influenza vaccination far outweigh any potential associated risks.
Secondary or Co-infections:
Bacterial co-infections significantly increase the morbidity and mortality associated with influenza, both in seasonal outbreaks and pandemics. Research indicates that bacterial co-infection occurs in most cases across all age groups. Individuals with underlying chronic conditions, particularly those who are immunocompromised, face the greatest risk of mortality.
Streptococcal pneumonia, Hemophilus influenza, and Staphylococcus aureus are commonly implicated in co-infections linked to influenza, often leading to bacterial pneumonia. History suggests many deaths occurred during the influenza pandemic due to secondary bacterial pneumonia. Other associations have been observed with invasive meningococcal disease and Clostridium difficile infections. While some studies suggest these associations decrease after accounting for seasonal patterns and temporal effects, further well-controlled studies across various climates are needed to access these relationships accurately.
Influenza virus infection is thought to promote bacterial infection by exposing more sites for bacterial adhesion. Impairing host immune responses and facilitating tissue destruction to allow bacterial colonization and spread. For instance, influenza can enhance S. pneumonia growth by increasing the availability of host-derived sialic acid as a nutrient source.
Influenza vaccination can potentially reduce secondary bacterial infections by limiting primary viral infections. Similarly, preventing and treating secondary bacterial infection may help alleviate the burden of influenza.
Conclusion:
The burden of influenza extends far beyond respiratory illness, encompassing a wide array of complications and secondary infections that significantly impact morbidity and mortality. From cardiovascular events to neurologic complications and from bacterial co-infections to exacerbations of chronic conditions, influenza poses a complex and multifaceted threat to public health. Understanding these consequences is essential for accurately assessing the true burden of influenza and implementing effective preventive measures. Through vaccination, early detection, and comprehensive management strategies, we can reduce the overall impact of the influenza virus.
