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)