SARS-CoV-2 was not the first virus to impact global health and it won’t be the last. In fact, health care professionals were so consumed with finding innovative technologies to fight COVID-19 that the attention to other well-known pathogens was suspended. This is the first blog in a series of three that addresses several respiratory viruses that still pose a threat to sensitive demographics. As we move toward an endemic, experts turn their attention toward two viruses that infect the respiratory tract and present similar clinical symptoms as COVID-19. Adenoviruses are non-enveloped, double stranded DNA viruses that are very diverse. Metapneumoviruses are enveloped, negative-sense single-stranded RNA viruses. These two viruses share COVID-19 symptoms and will be detectable via multiplex solutions in the near future.
Adenovirus and Metapneumovirus share common traits. Both viruses are transmitted through close contact (e.g., shaking hands or touching contaminated surfaces) or through the droplets from the nose and throat of infected individuals. Like influenza virus and RSV, human metapneumovirus infections are seasonal and circulation begins in winter and lasts through spring. Adenovirus infections are not seasonal, though there seems to be a peak in winter to early spring.
While adenoviruses can cause a wide range of illnesses (such as conjunctivitis, gastroenteritis, hepatitis, myocarditis), respiratory infections are the most frequent. Both viruses can cause upper and lower respiratory infections such as rhinitis, bronchitis, and pneumonia and symptoms can range from cough, nasal congestion, fever, to shortness of breath and chest pain.
Table1: Overview of human adenovirus and metapneumovirus
| Human Adenovirus | Human Metapneumovirus | |
|---|---|---|
| Family | Adenoviridae | Paramyxoviridae |
| Diversity | 7 species A to F (>70 genotypes) | 2 lineages (4 sub-lineages) |
| Viral Genome | linear, non-segmented double-stranded (ds) DNA | Linear, non-segmented, negative-sense RNA |
| Transmission | close contact or through the droplets from the nose and throat of infected individuals | |
| Seasonal | Year-round, peak in winter to early spring | Winter through spring |
| Disease | Can cause a wide range of illnesses. Respiratory infections are the most frequent. Can cause severe illnesses and death. | Upper and lower respiratory infections. Can cause severe illnesses and death. |
| Most at risk population | Elderly; patients with impaired immunity | Patients with impaired immunity; Elderly |
When talking about respiratory diseases, it is important to understand the respiratory tract. Every time we breathe, air flows in through the nose and mouth all the way to the end of the alveolar sacs in our lungs. Our respiratory tract is divided into the upper and the lower tract. The upper respiratory tract includes the mouth and nose, the throat (pharynx), and the voice box (larynx). The lower tract begins with the windpipe (trachea) and spans down through the bronchi and lungs. Most infections of the upper respiratory tract are caused by viruses but can also be caused by bacteria, fungi, and parasites. Upper respiratory tract infections are usually mild and self-limiting, whereas lower respiratory tract infections can be more severe. Overall, respiratory illnesses are the third leading cause of death in the world (after heart disease and stroke). (1)
For human adenoviruses and metapneumoviruses, most illnesses manifest with mild symptoms and are generally self-limiting. In fact, it is estimated that most children would have had an infection with both viruses by the age of 10. However, both viruses can infect any age group, and the risk for a severe illness is increased especially in the elderly and patients with weakened immune systems or other risk factors. It is important to note that human adenoviruses are responsible for about 3–7%, and human metapneumovirus for about 5% to 10% of hospitalizations of children suffering from acute respiratory tract infections (2). Studies also showed that metapneumovirus is a high-risk factor for the elderly and mortality rates of 50% have been reported. Severe manifestation of adenovirus infection is most likely in patients with impaired immunity and, if untreated, fatality rates may exceed 50%.
Given the wide overlap of clinical symptoms caused by different respiratory infections, it is important to know your enemy. This is especially true for patients with increased risks such as weakened immune systems. Accurate detection of the causative virus from a list of differential diagnoses is crucial for patient management and public health. Depending on the causative agent, appropriate infection control measures are needed to contain further infections and outbreaks.
The US Centers for Disease Control and Prevention (CDC) highlights that infection with human adenovirus or metapneumovirus can be confirmed using a polymerase chain reaction (PCR) based diagnostic test. Clinical laboratories already using PCR-based diagnostic devices can extend their testing portfolio using established workflows on existing infrastructure(Figure 1).
Figure 1: Schematic workflow – sample collection, sample extraction, setup/run PCR – results/report
Adenovirus References
https://www.cdc.gov/adenovirus/index.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955829/
https://doi.org/10.1055/s-0036-1584923
Metapneumovirus References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795268/
https://www.cdc.gov/surveillance/nrevss/hmpv/clinical.html
https://doi.org/10.1016/j.ijid.2014.03.1394
Statistics References
(1) https://pubmed.ncbi.nlm.nih.gov/32761743/
(2) https://virologyj.biomedcentral.com/articles/10.1186/s12985-021-01705-x
https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1185-x
https://www.sciencedirect.com/science/article/pii/S120197121401488X
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795268/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171713/