1.1 Available classes of diagnostic tests

In September 2020, the WHO set out their target product profiles for COVID-19 diagnostics, stating that only NAATs are recommended for confirmation of COVID-19 disease.14 Most NAATs have been based on reverse transcription polymerase chain reaction (RT-PCR), which enables highly sensitive and specific detection of viral RNA by targeting specific viral genes and amplifying the signal.8,14,15 Transcription-mediated amplification (TMA) is another technique used interchangeably with RT-PCR that involves the isothermal amplification of RNA by reverse transcription and subsequent generation of numerous transcripts by RNA polymerase.16 Loop-mediated isothermal amplification (LAMP) is a NAAT which utilizes an isothermal reaction that does not require the thermocycling process of RT-PCR.17-19Studies indicate that the LAMP technique is as highly specific as RT-PCR-based technologies but reports of sensitivities vary, with some studies reporting low sensitivity kits being marketed to developing countries.19-22 However, LAMP can be performed with minimal equipment and has been deployed to supplement widescale testing and/or where resources are limited.23
In cases where NAATs are unavailable, turnaround times are unacceptably slow, or near-patient NAATs are necessary, rapid antigen tests may facilitate earlier diagnosis.14,19 Antigen tests are typically immunoassays designed to detect SARS-CoV-2 proteins and require no amplification. As a result, these assays often require less instrumentation and can be performed rapidly, often in near-patient settings rather than laboratories.24,25 This class of tests may allow patients to self-sample and supports high-throughput testing.24-27 However, antigen tests offer reduced sensitivity compared with NAATs, so adoption of these tests needs to be appropriate to the needs of the patient population served or the defined use-case (e.g. screening for same-day travel).28
Whilst NAATs are capable of diagnosing current infection, antibody testing identifies exposure to the pathogen over the patient’s lifetime, supporting diagnosis later during the disease course.29 Antibody testing aids our understanding of COVID-19 and our immune response,30-33 the spread of infection,14,34-36 and, more recently, our response to vaccine administration and long-term efficacy.37