Diagnosing RSV

Unmet needs in diagnosing RSV

Diagnosis of RSV is key in identifying patients that need early treatment, to reduce both patient and socioeconomic burden, and in supporting infection control to minimise interactions between infected individuals and high-risk populations

Respiratory syncytial virus (RSV) is a common infection, occurring across all age ranges from infants to the elderly^1–3. As symptoms often include a runny nose and/or cough, which are usually mild, routine testing for RSV rarely occurs. This can result in infected individuals coming into contact with populations at high-risk of severe RSV, leading to preventable transmission of RSV.

Why is RSV not routinely tested for?

RSV is considered to be a mild, manageable infection in the majority of people, and for this reason a laboratory diagnosis may not be considered necessary¹. The symptoms are also very similar to other respiratory disorders, such as influenza, and in the absence of an RSV test, patients may be told they have a non-specific lower respiratory tract infection (LRTI)^4–7. Most RSV testing in groups at risk of severe RSV is carried out in infants with respiratory infections; elderly patients may not frequently undergo specific testing, as their respiratory secretions have a lower viral load than the secretions of children^1,7.

There is no approved treatment for RSV; the antiviral drug ribavirin has been used off-label in severely affected patients, although it is not used across all RSV patients due to its unfavourable safety profile⁸. Treatment is, therefore, usually based on relieving and managing symptoms, which in severe cases could involve hospitalisation, and ventilatory support^1,8.

More on antivirals and RSV treatment

Testing for RSV can be expensive⁷, and the absence of an approved therapy is likely to have a negative impact on the extent of RSV testing, as current treatment options are not specific to RSV.

Impact of limited RSV testing

While RSV causes mild symptoms in most people, in high-risk populations, including infants, adults aged over 65 years, and adults with comorbidities, RSV infections can present as pneumonia symptoms and bronchiolitis symptoms that require hospitalisation, and can result in death⁸.

Historically, RSV may not have been recognised as a common infection in adults¹; however, this viewpoint has changed with incidence reports of 1.5 million annual infections globally in adults over the age of 65 years³

RSV detection supports early treatment, identification of patients at risk of severe RSV, and infection control^9,10. Infection control is key in minimising the spread of contagious diseases such as RSV, as well as reducing morbidity, mortality and healthcare costs. For respiratory infections, such as RSV, infection control involves isolation of the patient, wearing of personal protective equipment (PPE) by healthcare professionals (HCPs), hand hygiene, and additional safety measures for any procedures, such as intubation, that may result in production of airborne particles¹¹.

Diagnosis of a specific pathogen is also key in determining appropriate treatment, and, as different bacterial and viral pathogens may cause similar respiratory symptoms, in the absence of RSV testing, antibiotics may be overused^10,12,13.

An early diagnosis of RSV or influenza using point-of-care (POC) testing can reduce the quantity and duration of antibiotic use, and the duration of hospital stays in adults and children, which has important implications for reducing socioeconomic impact as well as patient burden¹⁴

POC tests may also benefit patients by reducing the need for additional tests, such as blood tests and chest X-rays¹⁵.

As RSV is a seasonal infection, a clearer understanding of the number of affected patients is essential in preparing for infection control and assigning resources to treat patients with severe RSV during future seasons^16,17.

Without routine RSV testing, patients may not be identified at an early stage, potentially resulting in spread of infection, progression of disease in high-risk individuals, and increased use of healthcare resources (Figure 1).

Figure 1. Consequences of undiagnosed respiratory syncytial virus and transmission to high-risk patients^9,10,12,14. LRTI, lower respiratory tract infection; RSV, respiratory syncytial virus.

How is RSV diagnosed?

The diagnostics landscape for respiratory syncytial virus (RSV) infection is a growing area, with historical methods being replaced by more sensitive, faster techniques that are able to provide healthcare professionals with the information they need to optimise care of a patient with RSV.

Diagnostic samples for RSV

Diagnostic samples are collected using nose, or nose and throat swabs (nasal swabs or nasopharyngeal swabs, respectively)^1,13,18. These samples contain the virus that has been released from infected cells (viral shedding).

Viral shedding starts after RSV infection, and continues for about 10–11 days^7,19

Serum samples can be used with the immunofluorescence diagnostic technique to detect the presence of RSV antibodies. This method doesn’t directly detect the virus, but can determine whether a patient has been infected; analysis of serum samples is not useful as a point-of-care (POC) test as it doesn’t identify patients who are still infected²⁰.

Diagnostic methods for RSV

A range of methods can be used to diagnose RSV (Figure 2).

Figure 2. Strategies to diagnose RSV^{7,10,13,20,21}. DNA, deoxyribonucleic acid; RSV, respiratory syncytial virus.

Nucleic acid amplification testing (NAAT)^{7,10,13,22–25}

• The most common method is the polymerase chain reaction (PCR), which amplifies short specific sequences of RSV DNA that can be detected using a DNA-specific labelling chemical or fluorescence
• This method is used for nose and throat samples
• PCR must be performed in a laboratory
• Methods based on PCR are usually considered to be more sensitive than antigen-based methods
• In some cases, testing for multiple viruses and bacteria using PCR (multiplex PCR) may be more cost-effective than other methods designed to detect a single pathogen

Antigen detection^{7,10,12,21–25}

• This method utilises labelled antibodies that detect RSV protein
  • Immunofluorescence uses antibodies that emit a fluorescent signal when bound to RSV in nose and throat samples or RSV antibodies in serum samples
  • Enzyme-linked immunosorbent assays (ELISAs) use a combination of antibodies and enzymes that generate a measurable product when bound to RSV in nose and throat samples
  • Immunochromatography employs antibodies that produce a coloured product when in contact with RSV in nose and throat samples
• Antigen-based methods do not amplify the virus present in the sample, and are not as sensitive as methods that are based on amplification (NAAT and viral culture)
• Some commercially available immunochromatography tests (rapid antigen tests or lateral flow tests) may provide results in less than 30 minutes
• Rapid antigen tests are often less expensive than PCR-based methods, and do not require any specialised equipment to obtain results

Viral culture^20,25

• This method involves the incubation of patient nose and throat samples with cultured cells
• RSV infection of the cultured cells is detected using antigen-based methods
• Viral culture must be performed in a laboratory
• Several days may be required to observe RSV produced by cultured cells grown in a laboratory

Currently, NAAT and antigen detection are more commonly used than viral culture to detect RSV^21,26.

When selecting a diagnostic test, the speed of tests must be balanced against their sensitivity, while also considering the options available in a particular healthcare setting and any regulatory requirements²²

It is important to consider the viral load of the sample, as samples from older adults may have lower RSV viral loads than samples from children, and require a more sensitive detection method⁷. For this reason, antigen-based methods that do not amplify the virus present in the sample may not be as commonly used in adults as in children⁷.

If diagnostic results are not readily available, treatment strategies need to be in place while results are awaited. As multiplex PCR methods continue to develop, diagnostic sensitivity and the provision of results in a clinically meaningful timeframe may become accessible within a single assay that tests for multiple pathogens^{10,13,27–29}. As a wider range of diagnostic techniques become available, healthcare professionals must consider how best to incorporate these into their clinical decision-making to ensure that patients are offered the correct treatment for RSV infections^10,13.

More on managing RSV

References

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