Introduction
Since the outbreak of COVID-19 there has been an unprecedented effort
from the scientific community to develop tools to help tackle this
crisis. According to the Foundation for Innovative New Diagnostics
(FIND; 18 March 2021) there are 1025 commercialized SARS-CoV-2 assays
currently available and an additional 98 in development, including 655
immunoassays and 437 molecular assays.1 Early in the
pandemic, molecular testing using nucleic acid amplification tests
(NAATs) became the pillar of COVID-19 diagnostics. Since then, the
development of antigen tests, immunoassays, point-of-care, and
centralized options means there are now choices to be made as to how,
when, and where to deploy these technologies and many guidelines have
been developed, often based on Centers for Disease Control and
Prevention (CDC) and World Health Organization (WHO)
guidance.2-4 However, with the rapid emergence of new
technologies and new scientific data, these guidelines are very fluid
and subject to change. Furthermore, while NAATs are the most sensitive
diagnostic tool for COVID-19 infection,3-5 the global
demand for diagnostic testing is still such that the use of
labour-intensive, specialist techniques needs to be carefully
considered.
The aim of this review is to provide an international evaluation of
real-world testing needs and to define: settings where the ‘next best’
alternatives to NAATs are appropriate; settings where NAATs may not be
the best option; how to manage antigen test results; and how to manage
negative NAAT results where there is still a strong clinical suspicion
of COVID-19. We will further aim to set out the key considerations for
defining a testing strategy. Table 1 demonstrates that each testing
strategy provides different information on infection status and has
different performance metrics, so the right option for the right setting
needs to be carefully assessed. Here we also discuss the common
challenges facing clinicians and laboratorians when interpreting and
supplying COVID-19 diagnostics and provide insights into what will be
needed next.
Table 1. A summary of the diagnostic testing methodologies for COVID-19.