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