Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus 2: A Narrative Review

Abstract

Diagnostic testing to identify persons infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction-based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS-CoV-2 infection. Here, the authors review the current array of tests for SARS-CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.

Keywords: Antibodies; Antigens; COVID-19; Cells; Infectious disease immunology; Nucleic acids; Prevention, policy, and public health; Pulmonary diseases; Research laboratories; Upper respiratory tract infections.

Figure 1.

Examples of use cases for diagnostic testing among persons with proven or suspected COVID-19. A test well suited for one use case (such as epidemiologic surveillance) may be completely inadequate for another (such as rapid screening of symptomatic patients for allocation of personal protective equipment). For test results to enable a specific clinical decision, test developers, policymakers, and clinicians need to consider each of these with respect to the intention of testing and the population being tested as specifically as possible. For the moment, most use cases placed above the green and gray bar are best met by nucleic acid amplification tests, whereas detection of host-derived antibodies directed against SARS–CoV-2 will be crucial for surveillance, epidemic forecasting, and determination of SARS–CoV-2 immunity. SARS–CoV-2 = severe acute respiratory syndrome–related coronavirus-2.

Figure 2.

Heat map showing the adequacy of principal assay types (rows) for 4 key use cases. * This assumes that assays in development or currently undergoing regulatory evaluation prove to be accurate. † The utility of antibody detection assays for diagnosing acute infections is probably very limited around the time of symptom onset, when viral shedding and transmission risk seem to be highest. Thus, although such tests may have a role among persons presenting late in the course of their infection, the potential for misuse is high.