Discussion
Available diagnostic
methods
Criteria for choosing tests in resource-constrained
settings
The World Health Organization (WHO) has published the ASSURED
(Affordable, Sensitive, Specific, User-friendly, Rapid and robust,
Equipment-free, and Deliverable to end-users) criteria (Kosack et al.,
2017) that may be used as a benchmark for identifying the most
appropriate diagnostic tests for resource-constrained settings. However,
these criteria are non-specific and need to be adapted to each
diagnostic need, and not all test methods can be simplified to match the
ASSURED criteria.
Kosack et al. also identified six steps that must be additionally
addressed when selecting an in vitro diagnostic test: (a) define
the test’s purpose; (b) review the market and check each product’s
specification; (c) review the test’s regulatory approval; (d) obtain
data on the diagnostic accuracy of the test under ideal conditions (i.e.
in laboratory-based evaluations); (e) obtain data on the diagnostic
accuracy of the test in clinical practice; and (f) monitor the test’s
performance in routine use.
These six steps should all be considered when selecting an in
vitro diagnostic test for routine use.
Viral detection according to the clinical
course
The detection of viral particles (Mallett et al., 2020) (Siam et al.,
2020) or the corresponding immunological response (Deeks et al., 2020)
varies with post-infection time (Fig. 2). A systematic review concluded
that collecting samples early in the course of disease minimizes the
risk of false-negative results (Mallett et al., 2020).
Another systematic review of immunological response studies summarized
assay results for IgG, IgM, IgA, total antibodies, and IgG/IgM since the
onset of symptoms (Sethuraman et al., 2020). All showed low sensitivity
during the first week (30.1%, 95% CI 21.4–40.7), which increased in
the second week (72.2%, 95% CI 63.5–79.5), and peaked in the third
(91.4%, 95% CI 87.0–94.4) and fourth weeks (96.0%, 95% CI
90.6–98.3). Specificity was not evaluated according to time but was
generally high for IgM (99.1%, 95% CI 97.5–99.8) and IgG (98.6%,
95% CI 96.7–99.5).
Fig. 2. Estimated variation over time in diagnostic tests for
detection of SARS-CoV-2 infection relative to symptom onset (modified
from Sethuraman et al . 2020)