People around the world became familiar with the terms virus, virus shedding, virus transmission (surface and airborne), and incubation period during the COVID pandemic in 2020. To reiterate, shedding is the release of the virus into the environment from an affected host, through sneezing, coughing and even speaking. Transmission is the spread and the incubation period refers to the time from which the virus has entered a host’s body till the stage at which the host begins to present symptoms. However, did you know the above parameters are specific to each virus type? Additionally, the age and health of the affected host’s immune system further impact virus transmission.
For instance, an individual with an adenovirus infection may shed (release out) the virus for weeks, months, or even years.1 The indefinite duration of adenovirus shedding is due to the variations in the virus type, infection site and the host's immune system competency which influence the adenovirus infection type.
Let’s further explore adenovirus and its stages of infection, shedding duration and the implications of prolonged shedding that can last for years.
Adenovirus infection: What you need to know
What is an adenovirus?
Viruses, including adenovirus, are organisms smaller than a speck of dust and require advanced equipment to be examined. They cannot sustain themselves without a host (human beings, animals or plants).
Adenoviruses can infect animals and humans, but among the 100 different types of adenovirus, 49 can infect humans.2 The virus typically causes respiratory diseases, including occasional pneumonia, conjunctivitis and occasional gastroenteritis.3 Though adenovirus can affect people of all ages, young children and infants are susceptible because their immune system is still developing.2
Read more about What is adenovirus?
What is adenovirus shedding?
Viruses survive by multiplying in numbers within a host. When the host’s immune (defence) system is activated, it is imminent that the virus escapes the host to sustain itself. This process of virus release from the affected host is called shedding.4
What is the transmission of adenovirus?
The released viruses should enter another host (infect another human) to survive; the transfer of viral particles from one host to another is called transmission.4
Transmission of adenoviruses occurs through:3,5
- Micro-droplet inhalation: Airborne micro-droplets generated during breathing, speaking, coughing and sneezing by the affected individual
- Droplets of eye secretions
- Faecal-oral route
- Infected tissue or blood
Figure 1. Transmission of adenoviruses through airborne micro-droplets. Image by Hassan M. Pixabay [Internet]. Available from: Pixabay
What happens after adenovirus transmission?
Once the viral particles have successfully overcome the environmental challenges and the defence barriers (skin, mucus), they enter the next host. If the entry of viral particles is in large numbers and the host cells are permissive, the host infection is initiated.4
The viral particles multiply in numbers within the new host and during this invasion, the local immune system becomes activated. The affected host soon develops symptoms, which indicates the trigger of the body's defence response to the viral infection.
For adenovirus, it takes anywhere between 2 to 14 days for the symptoms to develop as the success of infection depends on the adenovirus type, viral load (numbers transmitted), transmission route, permissive cell accessibility and the host immune system competency.2,5,6
Permissive cells and adenovirus infection
Specific receptors on cells act like gateways for the invading viruses and if these cells further aid viral multiplication, they are said to be permissive.7,8
The permissive nature of the cells determine the infection type. Cells in the respiratory tract, gastrointestinal tract or eye conjunctiva are permissive to adenovirus (adenovirus type dependent), thus successfully multiplying in numbers.6
The multiplied viral particles then lyse (split open) the infected host cells, releasing the new viruses to infect neighbouring host cells or be shed from the body.
How long does adenovirus shedding last?
The adenovirus shedding duration cannot be narrowed down to a specific time-frame because the adenovirus type, infection site and the host's immune system competency affect the viral shedding.
How long does an adenovirus shed in the immunocompetent?
With a normal immune response to adenovirus infection, the shedding of adenoviral particles lasts for one or two weeks (post-infection) in immunocompetent adults,9,10 after which the immune system clears any remnant viral particles in the host.
However, in children with generalised adenovirus infection, shedding from the throat and stool occurs for months (3 to 6 weeks).10
Table 1. Post-infection adenovirus shedding duration depends on the virus type and site of infection
Adenovirus type | Site of infection | Duration (days) |
Human adenovirus 3, 4, 710 | Respiratory tract | |
Throat | 1 to 3 | |
Nose | 3 to 5 | |
Human adenovirus type 12, 18, 31, 40, 419 | Gastrointestinal (GI) tract | 7 to 14 |
Human adenovirus 3, 710 | Throat | 3 to 5 |
Nose | ||
Eyes | ||
Stool | ||
Human adenovirus 8, 19, 37, 53, 54, 5610 | Conjunctiva of the eye | 14 |
How long does adenovirus shed in the immunocompromised?
People with a weak immune system are said to be immunocompromised. One could have a weak immune system congenitally, due to a disease or an ongoing treatment.
When an immunocompromised individual is infected, the symptoms are prolonged due to poor immune response. The virus shedding is slow or delayed due to a lack of potential eradication threats by the already poor immune response.
Though there is limited data on adenovirus shedding in people that are immunocompromised, shedding is expected to last for months or even years.5,10
Understanding adenovirus latency: How it leads to prolonged shedding in infections
What is adenovirus latency?
Not all transmissions incite active infections, a few may undergo abortive infections (failed viral multiplication). Cell permissiveness, adenovirus type and the host immune status determine the fate of the abortive infections. Abortive infections mean the immune system destroys the transmitted adenovirus or latency.3
Latency is when the viral genetic material becomes inserted into the host genome and does not actively multiply. Once integrated into site-specific (lymphoepithelial tissues, kidney parenchyma, GI tract, tonsils and adenoids) chromosomes, the adenovirus genetic material replicates continuously with the host genome.
The condition is dormant because no infectious adenovirus is produced, hence, there is no adenovirus shedding.3,6,11
As the virus continues to reside in the host for a long time (months or years), the latent adenovirus is said to be persistent.
How does latent adenovirus cause infection?
Reactivation of the latent (dormant) adenovirus can occur due to immunosuppression, other viral infections (a compromised immune system), physiological changes (trauma, sunlight exposure, menstruation), and host molecular changes to produce infectious adenovirus particles in the cells harbouring the viral genetic material.11,12
Reactivation of latent adenovirus can be asymptomatic in the immunocompetent or cause multi-site infection in the paediatric group or immunocompromised people.5,6,10
What is persistent adenovirus-induced asymptomatic shedding?
The adenovirus shedding can occur even if the individual with reactivated adenovirus infection does not develop symptoms. Adenovirus has been detected in stool long after none were detected in the nasopharyngeal washings of asymptomatic individuals, indicating prolonged adenovirus shedding.11
Monitoring shedding duration becomes difficult for asymptomatic individuals as recovery progress cannot be tracked unless quantified.
FAQs
Why is knowledge of adenovirus shedding necessary?
Adenovirus shedding influences its transmission and infection. Understanding the adenovirus shedding from symptomatic and asymptomatic individuals helps determine the preventive measures, including isolation, to control its spread.13,14
Due to the lack of a specific duration for adenovirus shedding, existing guidelines lack a minimum duration of recommended precautions.13
Does adenovirus shed while dormant in the host?
No, adenovirus does not shed while dormant in the host. The viral genetic material persists in the host without active multiplication. However, a stimulus would reactivate the latent or dormant adenovirus to infect the harbouring cells by multiplying. The multiplied adenovirus shed after.
Why is there currently no adenovirus vaccine for the general public?
The adenovirus vaccine available contains live, non-attenuated (unaltered) adenovirus type 4 or type 7 in tablet form. The oral vaccine is administered only to U.S. military recruits and Coast Guard cadets.
The vaccine has excellent efficacy. However, its recipients shed adenovirus fecally for a month. The effect of the fecally shed adenovirus from the vaccinated on the general population, including the immunocompromised, is not been studied. Hence, the vaccine is restricted to U.S. military recruits to prevent the prevalence of adenovirus infections and morbidity.15
Why and how is adenovirus shedding quantified?
Quantifying adenovirus shedding helps understand the adenovirus load and infection severity. The viral load assessment with treatment tracks its effectiveness.
The viral load in the sample indicates viral shedding. The results assist in assessing the control measures to restrict adenovirus transmission to the population and environment.
Quantitative PCR estimates the viral load in clinical samples and diagnoses adenovirus infection. Quantitative PCR can help establish acute adenovirus infection from persistent adenovirus infection.
Summary
- Adenovirus shedding could last for weeks, months, or even years
- Adenovirus type, infection site and the host's immune system competency affect the viral shedding and its duration
- Prolonged adenovirus shedding could occur in children and the immunocompromised
- Latent adenovirus develops persistent infection upon reactivation after years, resulting in asymptomatic shedding or infection
References
- Kremer EJ. What is the risk of a deadly adenovirus pandemic? PLoS Pathog [Internet]. 2021 Sep 2 [cited 2024 Aug 11];17(9):e1009814. Available from: https://dx.plos.org/10.1371/journal.ppat.1009814
- Usman N, Suarez M. Adenoviruses. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 August 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559072/
- Doerfler W. Adenoviruses. In: Baron S, editor. Medical Microbiology [Internet]. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2024 August 11]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8503/
- Flint J, Racaniello VR, Rall GF, Skalka AM, Enquist LW. Principles of virology. 4th ed. Vol. 1. Washington DC: ASM Press.
- Al-Heeti OM, Cathro HP, Ison MG. Adenovirus infection and transplantation. Transplantation [Internet]. 2022 May [cited 2024 Aug 11]; 106(5):920–7. Available from: https://journals.lww.com/10.1097/TP.0000000000003988
- Arnold A, MacMahon E. Adenovirus infections. Medicine [Internet]. 2021 Dec 1 [cited 2024 Aug 12];49(12):790–3. Available from: https://www.sciencedirect.com/science/article/pii/S1357303921002607
- Greber UF, Flatt JW. Adenovirus entry: from infection to immunity. Annu Rev Virol. 2019 Sep 29;6(1):177–97.
- Albrecht T, Fons M, Boldogh I, Rabson AS. Effects on cells. In: Baron S, editor. Medical Microbiology [Internet]. 4th ed. Galveston (TX): University of Texas Medical Branch at Galveston; 1996 [cited 2024 Aug 12]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK7979/
- D’Souza DH. Update on foodborne viruses: types, concentration and sampling methods. In: Advances in Microbial Food Safety [Internet]. Elsevier; 2015 [cited 2024 Aug 13]. p. 102–16. Available from: https://linkinghub.elsevier.com/retrieve/pii/B9781782421078500050
- Ison MG, Hayden RT. Adenovirus. Hayden RT, Wolk DM, Carroll KC, Tang YW, editors. Microbiol Spectr [Internet]. 2016 Aug 12 [cited 2024 Aug 13];4(4):4.4.41. Available from: https://journals.asm.org/doi/10.1128/microbiolspec.DMIH2-0020-2015
- Radke JR, Cook JL. Human adenovirus infections: update and consideration of mechanisms of viral persistence. Curr Opin Infect Dis [Internet]. 2018 Jun [cited 2024 Aug 14];31(3):251–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367924/
- Traylen CM, Patel HR, Fondaw W, Mahatme S, Williams JF, Walker LR, et al. Virus reactivation: a panoramic view in human infections. Future Virol [Internet]. 2011 Apr [cited 2024 Aug 14];6(4):451–63. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142679/
- Huh K, Kim I, Jung J, Lee JE, Jhun BW, Gu SH, et al. Prolonged shedding of type 55 human adenovirus in immunocompetent adults with adenoviral respiratory infections. Eur J Clin Microbiol Infect Dis [Internet]. 2019 Apr [cited 2024 Aug 14];38(4):793–800. Available from: http://link.springer.com/10.1007/s10096-019-03471-9
- Shaikh N, Swali P, Houben RMGJ. Asymptomatic but infectious – The silent driver of pathogen transmission. A pragmatic review. Epidemics [Internet]. 2023 Sep [cited 2024 Aug 14];44:100704. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1755436523000403
- Gray GC, Erdman DD. Adenovirus vaccines. Plotkin’s Vaccines [Internet]. 2018 [cited 2024 Aug 15];121-133.e8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151885/