Influenza as a systemic disease in adults: clinical burden and benefits of vaccination

ABSTRACT. Influenza is a disease with systemic effects that extend beyond the respiratory tract and contribute to a wide range of extrapulmonary complications. Cardiovascular events, neurological manifestations, functional decline, progression of frailty, and metabolic disturbances are increasingly recognized as significant contributors to influenza-related morbidity and mortality, particularly among older adults and individuals with chronic medical conditions. Vaccination remains a key element of influenza prevention and is consistently associated with reductions in influenza-related morbidity, hospitalization, and mortality rates. Beyond its direct protective effects against infection, accumulating evidence suggests that the administration of seasonal influenza vaccine can provide broader health benefits, including cardiovascular protection, reduction of chronic disease exacerbations, preservation of functional status, support of healthy aging, and reduction of antibiotic use. Ongoing advances in vaccine development, including broadly protective influenza vaccines, mRNA-based platforms, improved vaccine formulations for older adults, and novel mucosal vaccination strategies, have the potential to improve protection against seasonal and emerging pandemic influenza viruses. Meanwhile, seasonal influenza vaccination coverage rates among older adults and people with chronic conditions are still much below the targeted 75%; hence increasing influenza vaccination rates remains a global public health priority. Recognizing that influenza is a multi-systemic disease and understanding the broader benefits of the vaccination against influenza in adults can help strengthen prevention strategies and reduce the global influenza burden.

For citation: Oktay Z, Tanrıöver MD. Influenza as a systemic disease in adults: Clinical burden and benefits of vaccination. Therapy (Moscow). 2026;12(5S):58–66.
https://dx.doi.org/10.18565/therapy.2026.5-s5.58-66

INTRODUCTION

Despite advances in vaccination, antiviral therapies, and surveillance systems, influenza continues to impose a substantial global health burden. According to the World Health Organization (WHO), seasonal influenza causes approximately one billion infections annually, including 3–5 million cases of severe disease and an estimated 290,000–650,000 respiratory-related deaths each year [1]. Current surveillance data from the United States Centers for Disease Control and Prevention (CDC) for the 2025–2026 season further demonstrate ongoing significant influenza activity across multiple regions, underscoring its continuing public health importance [2]. Similarly, European respiratory virus surveillance data have reported substantial influenza-associated hospitalizations and severe acute respiratory infection (SARI) activity during recent influenza seasons, highlighting the continuing burden of influenza on healthcare systems across Europe [3].

The clinical burden of influenza is particularly evident among older adults. Global mortality estimates indicate that approximately 67% of influenza-associated respiratory deaths occur among individuals aged ≥65 years [4]. In addition, data from the Global Influenza Hospital Surveillance Network (GIHSN), a multinational hospital-based surveillance platform, have shown that adults aged ≥65 years experience a 2.2-fold higher risk of influenza-related death compared with younger adults [5]. Similar findings have been reported from Türkiye, where more than half of hospitalized adults with laboratory-confirmed influenza were aged ≥65 years and nearly 70% of in-hospital deaths occurred in this age group [6].

Although influenza is traditionally regarded as an acute respiratory infection, its clinical consequences extend beyond the respiratory tract. In addition to pneumonia and other pulmonary manifestations, influenza has been associated with a wide range of extrapulmonary complications, including acute cardiovascular events, neurological disorders, functional decline, and exacerbation of chronic medical conditions [7–13]. These complications contribute substantially to influenza-related morbidity and mortality, particularly among individuals with underlying comorbidities. Chronic conditions such as diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy have consistently been associated with an increased risk of severe influenza-related outcomes [6].

As populations age and chronic diseases become more common, the burden of influenza is likely to remain substantial. Vaccination is the most effective strategy for prevention and reduces influenza-related illness, hospital­ization, and mortality [14, 15]. In addition to preventing infection, vaccination may also help reduce cardiovascular complications, preserve functional status in older adults, and decrease antibiotic use [14, 16].

This review focuses on the clinical burden of influenza in adults and the broader benefits of influenza vaccination. We discuss influenza as a systemic disease, summarize its major extrapulmonary complications, examine both the direct and broader health benefits of vaccination, and highlight emerging developments in influenza vaccine research and prevention strategies aimed at reducing the burden of disease in adult populations.

VIROLOGY AND EPIDEMIOLOGY OF INFLUENZA

Influenza viruses belong to the Orthomyxoviridae family and are classified into types A, B, C, and D. Influenza A and B are responsible for seasonal epidemics in humans, whereas influenza C usually causes mild sporadic infections and influenza D primarily affects cattle with no established role in human disease. Viral classification and pathogenicity rely on two major surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA) [17].

Influenza remains a major public health concern because of its ability to cause both seasonal epidemics and occasional pandemics. Seasonal epidemics occur annually and are primarily driven by antigenic drift, the gradual accumulation of mutations in viral surface antigens that enables the virus to evade pre-existing immunity, and are associated with substantial morbidity and mortality, particularly among vulnerable populations [18]. In contrast, pandemics arise through antigenic shift, a major genetic reassortment event that generates novel influenza A viruses against which population immunity is limited. In addition, zoonotic influenza viruses, including avian strains such as H5N1 and H7N9, continue to pose a persistent pandemic threat due to their potential for cross-species transmission and adaptation to humans [17].

CLINICAL PHENOTYPES AND PULMONARY MANIFESTATIONS

Influenza infection is generally classified as uncomplicated or complicated disease. Uncomplicated influenza is a self-limited acute illness characterized by constitutional and respiratory symptoms without evidence of organ dysfunction or extrapulmonary complications. In contrast, complica...

Zeynep Oktay, Mine Durusu Tanrıöver