What Distinguishes Adenovirus From COVID-19?

Overview

As of October 2024, approximately 25 million people in the UK have been infected with COVID-19, with 230,000 deaths according to the World Health Organization (WHO). Global cases have reached more than 776 million cases, with over 7 million deaths. Compared to the recent outburst of COVID-19 infections, cases of adenovirus infection have been reported for much longer, dating back to 1953.¹

Despite both being respiratory viruses, there are various differences that distinguish the two, including their transmission route, viral structure, genetics, and pathophysiology. Understanding these differences is important in improving prevention strategies and treatment approaches.

Transmission and epidemiology

COVID-19

Mode of transmission

According to the World Health Organization, COVID-19 can spread through:

• Short-range aerosol transmission - A person can come into contact with the virus by conversing with an infected individual. The virus is spread via small liquid particles released when speaking, singing, coughing or sneezing
• Droplet transmission - A person can directly touch the nose or mouth of an infected individual. This can also occur indirectly if an individual touches a surface that contains the viral particle
• Long-range aerosol transmission - Viruses can transmit in poorly ventilated and crowded areas, as viral particles are suspended in the air

Risk factors

Following the first case in Wuhan, China, in December 2019, severe cases have been reported more frequently in older patients. Susceptibility to COVID-19 in children below the age of 10 is significantly lower than in young/middle-aged adults. Whereas, individuals over 60 years old show greater susceptibility.² 

Other than age, certain diseases can increase the risk of severe COVID-19, including:

• Lung diseases (e.g., tuberculosis, cystic fibrosis, asthma, chronic obstructive pulmonary disease (COPD))
• Blood cancer
• Neurological disorders
• Chronic liver disease
• Dementia 

The risk of animals infecting humans with COVID-19 is low, however, at close contact, there is a high possibility of humans infecting animals. Animals spread COVID-19 usually through food products, such as meat and milk.

Adenovirus

Mode of transmission

Adenovirus can be transmitted via:³ 

• Inhalation of droplets
• Exogenous sources (e.g., pillows, linens, and lockers)
• Oral-faecal transmission
• Contaminated water

The risk of infection increases in closed and crowded areas with poor ventilation.⁴ Studies also show substantial evidence of cross-species transmission of adenovirus.⁵

Risk factors

Although adenovirus infection has no limited seasonality, cases are most frequent during spring and winter, particularly in young children.³ Immunocompromised individuals are known to have a greater risk of severe adenovirus infection. This includes those who have/had:

• Stem cell transplants
• Cancer
• Human immunodeficiency virus (HIV)
• Cardiac conditions

Studies show that people with high serum lactose dehydrogenase (LDH) have a higher risk of severe infection, possibly due to increased organ damage by LDH.⁶

Virology and structure

COVID-19

COVID-19 belongs to a large family of respiratory viruses, called coronaviruses, which also includes Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome (SARS). COVID-19 is a single-stranded RNA virus coated with an envelope expressing spike proteins. The genome size of COVID-19 is around 26 to 32 kilobases.⁷ The genetic content of COVID-19 includes the ORF1a/b genes which code for proteins required for viral replication and activity.⁸ This includes:

• Envelope protein (E)
• Spike protein (S)
• Nucleocapsid protein (N)
• Membrane protein (M)

The S proteins target the ACE2 receptors on the host cell surface, allowing attachment and infection. The RNA viral content is released into the cell allowing for the replication of the viral particles.^8,9

Adenovirus

Adenovirus belongs to the family Adenoviridae and is a non-enveloped double-stranded DNA virus with a genome of 26-48kb.¹⁰ Adenovirus binds to CAR, CD46 or Dsg-2 receptors and is transported to the host cell cytoplasm.¹¹ DNA contents of the virus are released and enter the nucleus to be replicated.¹¹

Clinical manifestations and disease course

Symptoms

COVID-19 and adenovirus infections share similar symptoms, such as:

• Fever
• Sore throat
• Coughing
• Fatigue, tiredness

Some symptoms are limited to either infection. For example, COVID-19 infection is also associated with:

• Loss of taste
• Loss of appetite
• Diarrhoea

Meanwhile, adenovirus infections can cause:

• Pink eye conditions (conjunctivitis)
• Bladder inflammation
• Neurological disorders

COVID-19

Initial tissue damage is caused merely by viral replication, however, prolonged symptoms of COVID-19 are caused by the host immune response which recruits a range of immune cells and releases pro-inflammatory mediators (e.g., TNF-a, IL-1, IL-6, IFN-y).¹²

This is known as a cytokine storm, which triggers a series of events that ultimately lead to multiple organ failures, including acute respiratory distress syndrome (ARDS).¹³ The duration of COVID-19 infection can differ among patients, but generally, symptoms last for 2 weeks after 5 to 6 days of the asymptomatic phase.

Adenovirus

Adenovirus infection can affect the respiratory or the gastrointestinal tract depending on the mode of entry. Upon adenovirus infection, the endosomal membrane is ruptured, causing cytokine secretion which recruits immune cells.¹⁴ Symptoms of adenovirus usually last for around 2 to 3 weeks, after an incubation period of a few days. However, in immunocompromised patients, adenovirus particles can reside in the lymph node for months and be reactivated following an asymptomatic phase.³

Diagnosis and detection

Approaches taken to diagnose and detect COVID-19 and adenovirus are similar; both are dependent on clinical presentation and molecular tests. The latter includes polymerase chain reaction (PCR) tests, as well as antigen and antibody testing. Due to the larger and more rapid outbreak of COVID-19, its detection tests have become more accessible compared to adenovirus (e.g., self-testing antigen test kits).¹⁵

Treatment and prevention

Antiviral medicine

Some antiviral medicines have been approved for use in severe cases of COVID-19, such as:

• Paxlovid (Nirmatrelvir plus ritonavir)
• Sotrovimab
• Molnupiravir
• Remdesivir

These medicines directly target viral proteins or protein interaction between the host and the virus. For example, sotrovimab attaches to S proteins to block its interaction with the ACE2 receptor.¹⁶

Adenovirus has no approved antiviral medicines. Anti-adenovirus-specific drugs are currently being tested. That said, more general antiviral medicines, such as cidofovir, and donor leukocyte infusion, have been used to treat immunocompromised patients.¹⁷

Immunosuppressive drugs

Immunosuppressive drugs, such as corticosteroids and anti-cytokine blockers, suppress the host immune system to prevent tissue damage and inflammatory conditions. It is beneficial in treating pneumonia associated with COVID-19 and adenovirus infections.

For COVID-19 infections, corticosteroid use is limited to late-phase, severely ill patients, as their immunosuppressive properties can enable opportunistic fungal infections.¹⁸ If administered in early, less serious patients, the drug can suppress the immune response against viral replication, which ends up helping the viral infection. Immunosuppressive drugs are useful in late-phase infection because viral replication is much lower during this period.

For similar reasons, long-term prescription of corticosteroids is avoided, as animal studies have reported an increased risk of viral transmission.¹⁹ Nonetheless, immunosuppressive drugs are useful in relieving inflammation caused by COVID-19 and adenovirus. 

Vaccines

Production of vaccines for COVID-19 has been rapid and expansive. Multiple alternatives have been introduced, including those produced by Moderna, AstraZeneca, Pfizer, and Novavax. Similar to antigen testing, accessibility to COVID-19 vaccines has drastically improved during the pandemic stage, with many vaccine centres set up in local areas.

The general mechanism of the COVID-19 vaccine involves introducing viral S proteins that are unharmful to the body. These proteins can elicit an immune response, enabling you to produce antibodies to prepare for potential COVID-19 infections. The S proteins can be directly injected (protein subunit vaccine) or be produced by injecting viral RNA (mRNA vaccine) or harmless viral vectors (viral vector vaccine). Contrastingly, adenovirus vaccines are not available to the general public.

Summary