Is Point-of-Care Molecular Diagnostics Ready for Prime Time?

Is Point-of-Care Molecular Diagnostics Ready for Prime Time?

Point-of-care (POC) molecular diagnostics filled a critical testing niche during the COVID-19 pandemic. It’s now expanded to respiratory panels using a 4-plex design of major actionable pathogens with similar symptoms (COVID-19, influenza A, influenza B, and RSV).

LGC Clinical Diagnostics and GenomeWeb sponsored a recent webinar, Point-of-Care Molecular Diagnostics: Challenges and Opportunities. In it, Jeff SoRelle, MD, Assistant Professor of Pathology at UT Southwestern Medical Center and attending physician of Clinical Pathology and Molecular Genetic Pathology, discusses what to consider when implementing POC testing -- from the specimen type and source to how it's being collected.

To learn more and access an extensive Q&A session with Dr. SoRelle, download the webinar by clicking here, or on the button below.

Why use molecular diagnostics?

This analysis of DNA or RNA is useful for amplifying small amounts of material. Usually done with PCR, amplification can use other methods, such as isothermal amplification, which is being used more in the POC setting. It uses a single temperature to amplify a target.

Why amplify?

Microbiology is one of the few diagnostic scenarios with amplification. It's particularly effective for high sensitivity and detecting a small number of organisms and dead, damaged, or unculturable organisms. Quick turnaround is another significant benefit. Culturing a virus can take a few days and must be done in a specialized setting. With amplification, POC testing can provide results in less than 48 hours.

What are the challenges of amplification?

There are amplification issues, so the question is, “Will the interpretation provide clinically significant information?” With COVID, some people who were two weeks or more post-infection had positive CT values, but PCR positivity showed a very low level of virus present.

There can be technical challenges with amplification, such as contamination and inhibition, causing false positives. Contaminants from the extraction process or present in the sample can inhibit PCR.

Cost is another consideration. A PCR test has a retail price of around $100; an antigen test is $20 or less and can be purchased at local pharmacies. It’s important to assess the required sensitivity and performance of PCR versus faster, cheaper antigen testing.

How do specimens & collection methods compare?

Accuracy is usually inversely proportional to a specimen collection method’s invasiveness. Healthcare workers were in short supply during the pandemic and still are today, which makes self-collected samples attractive.

In the webinar, Dr. SoRelle shared studies examining the sensitivity of different specimens – nares swabs, oropharyngeal, nasopharyngeal, and saliva. Each has trade-offs when balancing comfort, invasiveness, and accuracy.

1. One article examined 16 studies representing almost 6,000 patients in various settings, including inpatient and outpatient. The authors found that sensitivity in the salivary amplification test was 83% compared to 85% for nasopharyngeal (the gold standard). ^[1]
2. A study conducted early in the pandemic found 97% sensitivity for nasopharyngeal, 90% for oropharyngeal, and 84% for nasal self-collection. Some more extensive studies show self-collection works, but it trends toward less sensitivity since patients aren’t as rigorous in collecting samples as healthcare workers. ^{[2] [3]}
3. In another study, healthcare workers collected specimens from patients referred for COVID testing. Then, a few days later, the patients did video-guided self-collected swabs at the testing facility. Self-collected had lower sensitivity but only with late infections, particularly after the two-week period. ^{[4] [5]}

Taking POC molecular diagnostics beyond COVID

For COVID, self-collection generally tends to have lower sensitivity. Nares swabs are similar to nasopharyngeal swabs, and saliva works well. Since other respiratory diseases may be in different parts of the respiratory tract, does the experience with COVID transfer to flu or RSV?

As early as 2007, several Wisconsin studies investigated the sensitivity of self-collected versus healthcare worker-collected specimens in flu testing. The sensitivity of nasopharyngeal worked well across three different studies, 94% to 100%. Nares swabs were 10% to 20% lower.

A recent study in California of flu testing found nasal sites are important. Even nasal versus mid-turbinate can have 15 points difference in sensitivity. Another observation was that nasopharyngeal specimens collected about four CT values higher than the nasal specimens. ^{[6] [7] [8] [9]}

In the case of RSV, like flu, do differences in the nasal site have an impact, and does PCR improve the nasal swab sensitivity for RSV?

A study of 100 children tested by nasopharyngeal found the POC test had robust sensitivity and specificity. Nasal RT-PCR boosted levels higher than POC antigen testing, making nasopharyngeal collection for RSV a suitable choice.

POC molecular diagnostics pros & cons

Testing can be done at the patient’s bedside or outpatient clinic. It decentralizes testing away from large laboratories notorious for taking a long time to process samples. It’s more cost-efficient and gets results to patients faster. Equipment needs are minimal. It also minimizes the burden on centralized labs.

POC testing requires extra administrative work. Everyone who performs the testing must be certified, trained, and tested to ensure they follow QC practices every time. These essential requirements provide accurate testing but place additional burdens on caregivers. POC tests also have a higher error risk because they’re less regulated.

Key considerations 

What do you (and will you) need for your clinical performance in general respiratory testing? It's recommended that it contain at least four actionable pathogens. Sample type is also essential.

There is some pressure to move towards easy-to-collect sample types. Health systems see an opportunity to provide less labor-intensive, less expensive testing that’s easier for their patients. But anytime we change the testing process and it's not FDA-approved, we need laboratory-developed testing protocols to confirm we’re working within acceptable limits.

Deciding to offer a new test is about what's best for the patients, the clinicians, and the lab. No matter what you choose, communicate with your providers so they understand a test’s limitations and other sample types or testing methods.

Key takeaways 

1. Self-collected specimens have 5-10% less sensitivity than healthcare worker-collected specimens.
2. COVID-19 saliva specimens are equivalent to pharyngeal, especially in the early infection period.
3. Alternative samples are not equal among respiratory pathogens.

To learn more and access an extensive Q&A session with Dr. SoRelle, download the webinar by clicking here, or on the button below.

References

1. Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2: A Systematic Review and Meta-analysis; Guillaume Butler-Laporte, MC. Alexander Lawandi, MD MSc. Ian Schiller, MSc. Mandy Yao, BSC. Nandini Dendukuri, PHD. Emily G. McDonald, MD. Todd C Lee, MD, MPH; JAMA Internal Medicine
2. Waggoner JJ et. JAMA Net. Open. 2022
3. Therchilsen JH et al. Diagnostics (Basel). 2020
4. Self-Collected versus Healthcare Worker-Collected Swabs in the Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2
5. Johan H. Therchilsen, Christian von Buckwald, Anders Koch, Susanne Dam Nielsen, Daniel B. Rasmussen, Rebekka Faber Thudium, Nikolai S. Kirkby, Daniel E.T. Rasschou-Pederson, Johan S. Bundgaard, Kasper Iversen, Henning Bundgaard and Tobias Todsen
6. Irving, Stephanie et. Clin Med Res, 2012 PMID: 22723469
7. Temte JL et al. PLOS Glob Public Health. 2023 PMID: 37224148
8. Goyal S et al. Influenza Other Respir Viruses. 2017 PMID: 2871903
9. Frazee BW et al. Ann Emerg Med. 2018 PMID: 29174837