The Benefits of Syndromic Testing for Respiratory Infections

Respiratory infections continue to be a problem coursing through healthcare. Not only is COVID-19 still active, but influenza, respiratory syncytial virus (RSV), and other pneumonia causing conditions can lead to severe complications if not treated early and with the right medication. But testing for viral and bacterial causes of respiratory infections can be tricky, especially in vulnerable populations—and where more than one infection can hit a patient at a time.

That’s especially true with RSV, which largely affects children and older adults. According to a 2023 report, RSV leads to 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths in older adults in the U.S. each year (J Clin Virol 2023; doi: 10.1016/j.jcv.2023.105399). More than three-quarters of RSV-related deaths happen in older adults as well. Because RSV presents clinically no different than influenza or SARS-CoV-2, identifying it through testing is critical to help treat vulnerable populations.

CLN spoke to Manish Patel, MD, RPH, FACS, FPMRS, chief medical officer at Vikor Scientific, a high complexity molecular laboratory in Charleston, South Carolina, and assistant professor of urology at the Medical University of South Carolina, regarding syndromic testing for respiratory tract infections, about why it’s the better way to proceed, and how to make testing better by addressing human error.

Patel also spoke to why it’s so important to test and treat them in an outpatient setting, before they become so sick that they need to be admitted to the hospital. He also addressed why the U.S.’s previous influenza B rates may not be as high compared to other countries as it may seem.

What are the benefits of syndromic testing for respiratory tract infections?

There are lot of benefits overall to molecular technology compared to the way we typically try to identify bacterial pathogens. Currently, when clinicians are suspicious of upper respiratory infections, many institutions rely on culture. But that’s not ideal for several reasons, including poor specimen collection and simply the fact that growing a pathogen in a culture is really difficult. What we’ve realized clinically from laboratory side is that if we can identify a pathogen using its own DNA and RNA, it’s much more accurate. Moreover, we can identify whether there is more than one pathogen involved. This is much better for patient care overall.

When you think of culture, it is amazing to me, as a physician of more than 25 years, that we’re using technology from 1882 in 2024. It doesn’t make sense for culture to be the standard of care when PCR molecular testing isn’t even new to this century. It’s technology from 1980. We’ve just learned how to improve it with the aid of new technology to make it faster and more reliable.

What is the impact of syndromic respiratory testing in at-risk populations, particularly when it comes to RSV in older adults?

It is vital for any at-risk population. Older adults particularly are more likely to be admitted to the hospital and ultimately face a sepsis protocol. The CDC has emphasized that time to treat and the ability to narrow the spectrum of antibiotics as critical. The narrower the antibiotic spectrum, the better it is for the patient and for antibiotic stewardship globally.

The goal should not be treatment in the hospital setting. It should be treatment in the outpatient setting to prevent patients from going to the emergency room and to prevent them from being admitted.

Why was influenza B activity so elevated in in the U.S. compared to other countries?

It’s not necessarily that the U.S. had higher rates, but because the U.S. has better detection rates than other countries. Our ability to both identify and then ultimately track those patients through our data systems — many countries do not do that and do not have the ability to even follow patients as along as we do. We’re the standard bearers in a lot of these situations. There are other countries that do well with testing and tracking, though, including Japan, some European Union Countries, and Great Britian.

What do laboratory managers have to take into consideration when validating their PCR workflows prior to the upcoming flu season?

From that standpoint, the laboratory needs to ensure it is identifying the right influenza virus. They also should carefully plan to manage the volume of testing and ensure their staffing and other resources are ready to maintain high quality.

In our laboratory, part of our planning and decision-making process is following closely what is happening across the globe, for example, the data coming out of Asia. This can help laboratories predict the percentage of patients in the US that might become infected and need testing.

How common are co-infections, particularly cases of both a viral and bacterial infection in one patient?

I recently gave a presentation at a scientific conference about a study where we evaluated more than 30,000 respiratory samples. We examined several parameters, including how often samples were positive for SARS-CoV-2 as well as secondary bacterial or viral pathogens, including RSV and influenza.

An alarming finding of this study was that up to 25% of samples had coinfections with bacteria, and very aggressive at that. We found Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, and others. I think this explains why we saw greater mortality among certain patient population during the COVID-19 pandemic.

This adds to the evidence that, in my opinion, utilizing only a limited viral panel for high-risk populations is nearly malpractice. The clinician has no other way to reliably predict which potential coinfection could be present. That’s the purpose of a large syndromic panel. The healthcare team often only gets one shot to get testing and treatment right before a patient ends up in critical condition.

What should a laboratory manager consider when evaluating a new syndromic testing solutions for respiratory pathogen detection?

I think it’s important to consider who the vulnerable population is, what they specifically are at risk for, and what those co-pathogens tend to be. Finally, we also need to consider the antibiotic resistance of those pathogens. Clinical pharmacologists or infectious disease experts can use that to further narrow or taper those therapies. These are elements that I think are necessary, which is why this is the way we develop panels at Vikor Scientific.

Is there anything else you’d like our readers to know that can help make testing better in this realm, especially as we approach flu season?

I think one of the important things to focus on is acquiring high quality respiratory samples. The laboratory should take the lead in teaching people proper sample collection techniques. A swab in the mouth or nasopharynx won’t always get enough sample to identify RNA or DNA for sample amplification. With a high quality sample, we can achieve a specificity of 99%. But sample collection quality is based on human skill, and human error can be reduced with proper training.

And finally, while rapid tests are also a piece of the puzzle for tackling respiratory infections, we should remember that antigen testing can have up to a 30% false negative rate, while PCR — again done appropriately — can achieve up to a 99% sensitivity and specificity.