Introduction

Influenza virus and adenovirus are both common respiratory viral infections. Influenza virus is responsible for influenza (flu) which is a contagious respiratory infection¹ and adenovirus is a common virus that causes respiratory infection that is similar to the flu.²

Influenza is a communicable virus that infects and colonises the upper respiratory tract, causing inflammation in the lungs.³ Influenza virus usually causes mild infection with the majority of patients recovering without any medical attention but influenza virus can cause complications in high-risk patients such as the elderly, children and pregnant mothers, making them sick and requiring treatments.³ The influenza virus circulates seasonally in temperate climates, where there are flu outbursts in the community every winter while in tropical climates, the influenza virus is present throughout the year.¹

Adenovirus are DNA viruses, found in both animals and humans and commonly infect both children and adults.⁴ The virus infects and colonises many organs in the body but most infections are mild or asymptomatic it can cause serious infection in immunocompromised individuals which will require medical treatments.⁴ Adenovirus is present all year around but infections peak during the winter and early spring.²

It is crucial to understand the difference between the two viruses to effectively manage and treat the infection. While both viruses may present similar symptoms such as high fever, coughing and sore throat^1,2, an accurate diagnosis is needed for effective treatment. Treatment for influenza will not be suitable for treating adenovirus infection. Moreover, adenovirus and influenza both have different routes of infection and understanding the difference is needed for prevention and control measures. This is necessary to prevent further patients from getting infected and to protect those who are at high risk. This article will discuss the difference between influenza and adenovirus. 

Virology

Structure and classification of influenza virus

There are four types of influenza virus:

• Influenza A virus: Influenza A and influenza B viruses are the most common type that is circulating and are responsible for seasonal flu epidemics. Influenza A virus is further classified into subtypes based on the surface protein combination of Hemagglutinin (HA) and Neuraminidase (NA).³ There have been more than 130 influenza type A combinations identified in nature⁵ but more can be found due to influenza's ability to reshuffle and rearrange its genes in a process called reassortment⁵
• Influenza B virus: Influenza B virus is milder compared to influenza A virus and is classified into lineages rather than subtypes. Influenza B virus can either belong to B/Yamagata or B/victoria lineage¹
• Influenza C virus: Influenza C virus causes mild infection and circulates less frequently and is therefore not considered a public health importance¹
• Influenza D virus: influenza D virus mainly infects cattle and is not known to infect and cause infection and illness in people¹

Genetic makeup

Influenza virus is classified as an RNA virus characterised by a single-stranded RNA genome rather than double-stranded DNA enclosed within a lipid envelope.⁶ Influenza virus’s RNA is also negatively stranded and segmented, meaning that viral proteins cannot be made until the RNA is converted into positive-stranded RNA using polymerase proteins.⁶ Surface proteins such as hemagglutinin (HA) and neuraminidase (NA) are embedded in the viral envelope.⁶ HA is important for infection as it binds the viruses to host cells while NA releases the newly formed viral particles from the infected cell, releasing it to infect more cells. The genetic makeup of influenza shows variability, with differences observed for each influenza type and between each strain within a subtype or lineage. This variability is due to mutations which can affect how virulent the virus is and the impact on the host organisms.

Structure and classification of adenovirus

Adenovirus are DNA viruses that infect both animals and humans. There are over 100 adenovirus types with 49 types infecting humans.⁴ Adenovirus can be split into two separate groups depending on what species they infect:⁴

• Avian adenovirus 
• Mammalian adenovirus 

Adenovirus can be further classified into seven species (A-G) depending on hemagglutinin properties, genetic information and the site of infection.⁷ Species A, D, F, and G infect via the GI tract, species B, C, E infect via the respiratory tract, species C through the eye and species B also through the urinary system.⁷

Genetic composition

Adenovirus is a non-enveloped, icosahedral capsid double-stranded DNA virus measuring 70 to 100 nm in size.⁴ The capsid (virus’s head) of adenovirus contains structural proteins such as fibre proteins and hexons. Fibre protein facilitates viral attachment to the host cell by binding to the Coxsackie-adenovirus receptor (CAR) which facilitates infection.⁸ Adenovirus codes have a linear double-stranded DNA encoding for over 30 proteins.⁸ The proteins are responsible for the virus to attach and infect host cells, to replicate within the host cell, to assemble new viruses and to escape the host cell whilst evading the immune system. 

Epidemiology

Influenza viruses in specific geographical regions in temperate regions occur every year during the winter season.³ There are around a billion cases of seasonal influenza occurring all around the world every year but the severity, length of influenza and age group infected varies during different influenza seasons depending on what type and strain of influenza is circulating.³

Influenza can affect everyone but in most cases, the infection is mild and is resolved with rest and no medical treatment. However, there are specific groups that influenza viruses cause complications:¹

• Children under 5 years old
• Pregnant women
• Elderly people
• Immunocompromised individuals such as HIV patients, or cancer patients receiving chemotherapy
• Individuals with chronic lung disease, such as asthma or COPD
• Individuals with chronic cardiac disease.
• Healthcare workers 

Influenza epidemics can cause individuals to be absent from work and school and also cause hospitals and health clinics to be overwhelmed.¹

Adenovirus is present throughout the year but most adenovirus epidemic is most prevalent during winter and early spring. Adenovirus infection can affect everyone of all ages but they are more common in children, especially from 6 months to 2 years old, and between 5 to 9 years old.⁴ Adenovirus is spread in children during nurseries and school as they are in close contact with each other and their hands are not frequently washed.² Adenovirus is spread in adults in crowded environments such as dorms or military rooms and in hospitals and nursing homes.²

Adenovirus infection is more severe in immunocompromised individuals, and can be fatal if there is no medical treatment. These can include individuals who have a weakened immune system and cannot fight off the viral infection:

• HIV/AIDS patients
• Cancer patients with recent chemotherapy
• Organ or bone marrow transplant
• Autoimmune disease like lupus or rheumatoid arthritis
• Chronic diseases like diabetes or chronic kidney disease

Clinical manifestations

Influenza symptoms

Influenza virus can vary from mild to severe infection. Most patients experience some or all of the following symptoms:¹

• High fever
• Cough and sore throat
• Runny or stuffy nose
• Headaches
• Fatigue
• Muscle and body aches
• Vomiting and diarrhoea (usually in children than adults)

Adenovirus symptoms

Most adenovirus infections are asymptomatic⁴ and symptoms of adenovirus infection depend on where the virus infects your body.² Adenovirus usually infects the respiratory system and has similar symptoms to the flu.²

These can include:

• High fever
• Cough
• Runny nose
• Sore throat 
• Pink eye
• Ear infection
• Pneumonia

When the virus infects the gastrointestinal tract, you can experience:²

• Diarrhoea
• Stomach aches
• Nausea
• Vomiting

If the virus infects the urinary tract, it can cause urinary tract infection². 

Transmission

Influenza virus is a contagious disease and spreads when an infected individual coughs, sneezes or talks and releases droplets that contain the virus.¹ Influenza spreads very quickly, especially in crowded places such as hospitals, nursing homes and schools.³

Adenovirus also spreads via airborne droplets when an infected patient coughs or sneezes, releasing the virus to other people. Adenovirus can also be transmitted through close contact from person to person through touching, shaking hands, hugging or kissing. It can also be spread through touching contaminated surfaces such as door handles and then touching your face before washing your hands². Adenovirus infections also occur via the faecal-oral route.⁴

Diagnosis

Influenza is diagnosed clinically in a lab as it's difficult to differentiate from other infections using clinical symptoms alone. Lab techniques are used to give quick results within an hour that is high sensitivity and specificity and these include:³

• Rapid Antigen tests
• Reverse transcription PCR

Adenovirus is usually detected using clinical symptoms but lab techniques are used and these can include:⁴

• PCR
• Viral antigen assay
• Serology
• Viral culture swab

Treatment and management

Most influenza cases do not need any medical treatment but in some high-risk individuals, as described earlier, treatment is needed to help clear away the infection. For mild symptoms, it is recommended that patients stay at home, rest and drink a lot of fluids.¹ For severe symptoms, antiviral medication is prescribed to kill the virus and provide symptomatic relief but this is usually given to hospitalised patients. Other treatments include providing asymptomatic relief by treating the symptoms of influenza infection like high fever, headaches and muscle aches.

Adenovirus infections are mostly asymptomatic and mild and treatments are focused on providing symptomatic relief.² This includes taking over-the-counter medicines to reduce fevers and pain relievers. It is important to rest and drink a lot of fluid when recovering from adenovirus infection. Antiviral medications are not effective against adenovirus and are not used to treat the infection.

Complications and prognosis

Influenza has a high infectious rate but most people recover from the infection without any treatment. However, influenza can become fatal in young children and elderly patients and those with compromised immune system and can cause the following complications:³

• Pneumonia
• Multiorgan failure
• Respiratory distress syndrome
• Myocarditis

Adenovirus has an excellent prognosis for individuals with infection, with the majority of people clearing the infection without any severe symptoms.⁴ However, for immunocompromised patients, the prognosis is poor, with a mortality rate of 70% for immunocompromised individuals.⁴ Complications associated with adenovirus include:⁴

• Bronchiolitis obliterans
• Disseminated adenovirus infection
• Bronchiectasis

Summary

Influenza virus and adenovirus are both contagious viruses that circulate during the winter seasons. They both share similar symptoms such as high fever, sneezing and coughing and similar routes of transmission. However there are distinct differences:

• Influenza is a RNA- virus whilst adenovirus is a DNA virus
• Influenza is only transmitted via airborne droplets but adenovirus can also be transmitted through touch, contaminated surfaces and faecal-oral route
• Influenza can affect a large range of the population with symptoms showing in most individuals, whilst most adenovirus infections are asymptomatic
• Influenza is more severe in children, the elderly, individuals with chronic health conditions and immunocompromised individuals whilst adenovirus is very severe in immunocompromised individuals only
• Influenza can be treated with antiviral medication which is not effective for adenovirus

Despite the many similarities between the viruses, it is important to be able to differentiate between the two, for effective treatment and management of the disease, to control and prevent outbreaks and to provide the best care to patients.