Opportunities and challenges of point of care testing paradigms in the post-COVID era

In this special issue of Expert Reviews in Molecular Diagnostics, leaders in our field have contributed papers related to the topic of ‘Point-of-care molecular testing for infectious diseases: in the wake of the COVID-19 pandemic.’ Point-of-care (POC) testing, which requires actions beyond clinical observation and evaluation of patient signs and symptoms, is not new. POC tests have been widely used to support clinical decision-making for many centuries [1] including urinalysis, microscopy, syphilis serology, blood glucose, and pregnancy testing just to list a few examples. So while POC tests have long been used in clinical settings, technologies of the twenty-first century are changing the landscape of on-site diagnostics in exciting, and sometimes challenging, ways.

Many of the more established POC tests have relied on microscopy, or on lateral flow assays (LFA) that can detect antigens, antibodies, or metabolites/enzymatic by-products of certain conditions and infectious agents. Examples of common POC LFA include rapid HIV tests, urinalysis dipsticks and strep A tests. While these have been available for decades, newer tests have begun to use molecular methods, most often nucleic acid amplification tests (NAAT), to detect DNA or RNA targets. This class of diagnostic assay has been most widely applied to the detection of infectious diseases because of the ability to rapidly, with high sensitivity and specificity, identify patients with infections and inform the immediate clinical management of those patients.

Unprecedented development has been seen in the fields of lateral flow technologies and molecular tools for diagnostics of infectious diseases over the last 4 years, fueled, in part, by the SARS-CoV-2 (CoVID-19) pandemic. Not only were laboratory-based assays created to detect this infection but several POC and home testing options became available within less than 2 years of identifying the virus! The developmental pathway for these tests was supported by enormous levels (in the billions of dollars) of governmental funding in the United States, Europe and elsewhere. Efforts were also facilitated by streamlined regulatory review processes which allowed the tests to be quickly marketed and distributed globally.

Having gone through this accelerated push for development, and in the context of somewhat declining demand for COVID-19 testing, developers have been adapting their technologies to address the need to diagnose other infectious diseases with POC, and for some infections, home-based testing. It is important to define these concepts for the sake of clarity: POC tests are generally designed for use by a professional in a healthcare, or quasi-healthcare, setting. They are intended to support a test-and-treat paradigm by quickly identifying the cause of symptoms and providing information to guide patient management and follow-up. Home-based testing, on the other hand, is completely controlled, performed, and interpreted by the consumer, and not the focus of this issue. It is worth noting that a home-based test (e.g. a pregnancy test) can be used in a clinical setting if desirable, but the converse is not true. Not all POC tests are appropriate for consumer use and interpretation.

The health-care landscape has changed enormously since 2020 with physicians, patients, and consumers now having expectations of access to immediate diagnostic answers. POC testing can support this rapid decision-making. Another area in which POC tests can have substantial impact is in managing appropriate therapy and supporting antimicrobial stewardship by specifically identifying one of many potential causes of infection. POC tests may fill all of these clinical needs, but there are challenges that come with every new opportunity.

It is important to carefully consider use-case scenarios before adoption of a POC in clinical settings. Even within a single setting, some patients may benefit from a POC test, while lab-based testing is more appropriate for others. An example is testing for Chlamydia trachomatis infections. For patients presenting with symptoms, a POC test is desirable as the symptoms may indicate a variety of conditions, of which chlamydia is only one possibility. Diagnosing the cause of the symptoms allows targeted therapy specific only to the pathogen/s detected. Conversely, if a young woman is being seen for routine healthcare and an annual chlamydia screening test is warranted based on guidelines, a lab-based test is sufficient (and likely more cost appropriate) since the pretest probability of infection is low and the patient is not expecting to receive treatment during this visit. Considerations of this type apply to many situations and thus careful selection of the best choice of test options is necessary.

In the articles comprising this special issue, assays that are commercially available or in development are described as well some of the considerations for adoption and implementation. These considerations include quality management, utilization in resource limited settings and best practices for selection of new tests. The articles are intended to provide a snapshot of where the field is today and what we expect to be coming in the next few years in this exciting phase of diagnostic assay development.

There are three reports that do not focus on specific tests or pathogen detection. The article by Baldeh et al. [2], describes lessons learned during COVID-19 pandemic regarding how to select the most appropriate test for a particular setting. The authors focus on issues of technical features and diagnostic accuracy as well as features related to ease-of-use, cost and data management. Similarly, Laryea and Nichols [3] discuss the importance of developing quality and risk management processes for all POC adopted into clinical care practice. This article provides useful insights on assessing potential sources of error and reducing the potential for those errors with the development of specific policies and procedures. Rakeman-Cagno and colleagues [4] also provide support for a call to maintain the capacity to perform POC tests, personnel and infrastructure, in non-pandemic periods by continuing to offer what POC tests are reasonable for the facility. They posit that the maintenance of such capacity will provide improved epidemic response capacity in the future, as well as supporting current patient care and management.

Two of the articles in this special issue, one editorial and one review, focus on the patient population which might be best served by POC tests with perspectives that can be applied regardless of the disease state in question. Brown and Hay [5] specifically call for further evaluation of POC tests in primary care patient populations. This is particularly important given that most of these assays are evaluated in settings where very high positive rates are expected in order to conduct the study as quickly as possible. This means that performance data are not available for lower prevalence settings such as primary care. With the expectation that the pretest probability of a positive result is much lower in primary care settings, it is important to understand the positive predictive value of POC tests to more accurately guide clinicians regarding next steps (e.g. immediate treatment or reflex lab testing for confirmation). Further, economic evaluation in these low prevalence settings will likely be very different than those performed in high-risk populations and thus decisions about whether to adopt tests are difficult to make based on the available evidence. In contrast, the review by Moerman and colleagues [6] focuses on the benefit of molecular POC tests in managing critically ill patients.

Focusing more specifically on types of infections/conditions are five articles describing POC tests for identifying causes of central nervous system (CNS) infections, identification of gut pathogens, and agents of pulmonary infections. Milburn et al. [7] review a variety of POC approaches including LFA and NAAT tests for diagnosis of CNS that can be used in resource constrained settings where central or reference lab testing is often unavailable or too delayed to be useful to patient management. The methods described include detection of biomarkers, antigens, antibodies, and nucleic acids. Granisteanu and colleagues [8] provide a similar review of technologies focused on understanding the causes of diarrhea and with an excellent discussion of the issues related to the implementation of these tests, including contextualizing result interpretation into the clinical presentation and other findings. Three articles, an editorial, a report, and a review, describe advancements in the area of pulmonary infectious disease diagnostics with a focus on the detection of fungal pathogens. Turbin and Azar [9] provide an overview of the advantages and appropriate use cases for these tests that are predominately LFA based. Aerts and colleagues [10] provide an in-depth review of the field and describe the potential for future developments, while Thornton [11] focuses on the options currently available for rapid diagnosis of mucormycosis.

This special edition is rounded out by two reviews that clearly demonstrate future application of POC tests that move beyond pathogen detection by focusing on the implementation science associated with the adoption of these assays. Grebely et al. [12] describe the clinical implications of POC testing in terms of Hepatitis C virus treatment and long-term care. Finally, in a review by Spinelli and Gandhi [13] a POC test that is used to monitor treatment adherence is described. These two articles shed light on the future of clinical management when incorporation of rapid, highly sensitive tools are available to inform patient management decisions.

Taken together, this series of articles provides useful information about where we are, and where we can, and should, be in the near future. Adoption of POC tests has associated costs and requires infrastructure, including personnel, and changes to clinic flow that must be justified in each clinical setting. However, the benefits of such adoption are likely to be profound, changing the provision of health-care services and providing improved disease management for patients. It is an exciting time to be in the field of rapid diagnostics, and the tools yet to come are limited only by the imaginations of assay developers.

Declaration of interests

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper was not funded.