Viral infections are a leading cause of morbidity and mortality worldwide. Globally, lower respiratory tract infections remain the 4th leading cause of death over the past 20 years. [1] In the United States, influenza and pneumonia have consistently ranked between the 6th and 9th leading causes of death each year. [2] As of October 2022, the COVID-19 pandemic has resulted in over 623 million cases and over 6.5 million deaths worldwide. [3] Collectively, these data demonstrate the significant burden that viral infections have on human health.

Due to the high prevalence of viral infections, it is imperative that they be diagnosed quickly and accurately to enable patient management decisions, including appropriate use of antimicrobials and selection of appropriate isolation precautions. Traditionally, diagnostic testing has been performed in a laboratory setting by trained personnel. However, laboratory-based testing can result in increased turnaround times, which can result in delayed patient care. To address this issue, point-of-care (POC) tests have been developed for certain viruses, such as influenza A/B, respiratory syncytial virus (RSV) and SARS-CoV-2. Point-of-care tests allow for samples to be collected where a patient is evaluated and often generate results in less than 30 minutes, which has the potential to enhance patient care. Rapid testing may play a significant role in the diagnosis of infectious diseases, often ensuring that appropriate antimicrobials are selected, and adequate infection control measures are taken. There is also a vital role for POC testing in resource-limited areas, where laboratory-based testing is impractical, and for patients who are unlikely to return for follow-up visits.

The COVID-19 pandemic accelerated the need for rapid, point-of-care testing at an unprecedented scale. In March of 2020, the U.S. Food and Drug Administration (FDA) issued the first emergency use authorization (EUA) for a POC COVID-19 test (Cepheid Xpert Express SARS-CoV-2 real-time RT-PCR) for use in healthcare settings operating under a Clinical Laboratory Improvement Amendments (CLIA), Certificate of Waiver, Compliance, or Accreditation. In May of 2020, the FDA granted EUA to the first rapid antigen COVID-19 test (Sofia 2 SARS Antigen FIA) for use in POC settings. There are now over 250 molecular tests and 50 antigen tests that have been granted EUA, with 21 molecular and 45 antigen tests authorized for POC testing in a waived setting. [4] It is important to note that the EUA status of these tests is only valid under the current public health emergency declaration, and following its termination, manufacturers will need to follow the traditional route of FDA review and approval through the 510(k) process or discontinue respective tests. For example, the BioFire Respiratory Panel 2.1, which includes SARS-CoV-2, was originally given EUA status and was submitted for market approval using the De Novo review pathway, which it was granted in March 2021.

The development of rapid nucleic acid amplification tests (NAATs) for POC diagnosis of COVID-19 has created an increased demand for POC NAATs for other viral infections. NAATs have the advantage of increased sensitivity over traditional antigen-based POC tests while providing rapid turnaround time. However, most NAATs require trained personnel to perform testing, and as a result, most NAAT-based tests are categorized as high- or moderately-complex. A requirement of POC tests (antigen and NAAT) is that they must be simple to use and designed to operate as “sample-to-answer” assays, meaning that all steps, including analysis and interpretation of data, are performed automatically. [5] In this review, POC is referring to testing that is near-patient or laboratory-based and includes both antigen- and molecular-based testing. At-home antigen and/or molecular tests are not considered part of POC testing within the scope of this review.

The primary advantages of POC tests are reduced turnaround times and subsequently more rapid clinical decision-making. In addition, POC testing can often be performed whenever patients present for evaluation, whereas laboratory-based testing may have reduced availability. Point-of-care antigen tests are often more affordable than laboratory- molecular tests, providing a cost-effective approach to screen patients for viral infections. It is important to note that in some cases, POC NAAT testing may be more cost effective if there are additional costs associated with confirmation of antigen test results. [6], [7], [8], [9], [10] Finally, POC tests generally offer high specificity, but false-positive results are possible, especially when the prevalence of disease is low.

Historically, the key disadvantage of POC tests has been lower sensitivity relative to laboratory-based molecular testing. One example is rapid antigen tests for influenza, which have reported sensitivities as low as 45%. [14,15] It is worth mentioning that there are guidelines provided by the FDA regarding expected sensitivity (positive percent agreement) and specificity (negative percent agreement). In general, antigen tests are expected to have a sensitivity ≥80% and while there are no minimum specificity requirements, most antigen tests are expected to have a specificity of ≥90%. For NAAT tests, sensitivity and specificity are expected to be ≥90% and ≥95%, respectively. [4]

Due to the reduced sensitivity and increased risk of false-negative results, the CDC has recommended that a follow-up NAAT be performed on patients clinically suspected of having influenza despite a negative POC test. [16]To overcome this limitation, there has been significant interest in the development of POC NAATs. A number of platforms have been successfully developed for POC testing and have been given waived status by the FDA, with high sensitivity (>95%) and fast turnaround times (< 60 minutes). [17] Some platforms offer multiplex testing, which has been previously limited to laboratory-based testing, providing a significant advantage for clinicians in POC settings in the collection of a single specimen for testing of multiple pathogens. While the regulation of POC testing will be discussed below, there has been concern about using NAATs in POC settings by non-laboratory trained personnel. This concern has revolved around the potential for contamination and the reporting of false-positive results.