Discussion
The study results demonstrated high agreement between the rapid RT-PCR
assay using the STANDARD M10 and the conventional RT-PCR using the
Allplex SARS-CoV-2 for detecting SARS-CoV-2 during the Omicron surge in
Korea. Discordant results between the two assays were observed in
specimens having low viral loads, which were reflected with high Ct
values.
Few studies have evaluated the clinical performance of STANDARD M10.
Hong et al. estimated the sensitivity of STANDARD M10 among 342 positive
samples proven by the conventional RT-PCR using the Allplex SARS-CoV-2
assay.8 They reported a sensitivity of 87.7% with
STANDARD M10 using simulation with a virtual specimen pool comprising
specimens having a Ct value of E gene ≥30 as 27.7%. In the
present study, STANDARD M10 detected 118 specimens among 123 positive
specimens that were positive with Allplex assay (95.9%), although the
positive specimens consisted of 34.1% of specimens with a Ct value ≥30
for E gene, which demonstrates acceptable clinical performance
based on the criteria by the Korean Ministry of Food and Drug Safety.
These findings suggest that clinical performance would be different
between the evaluation from manipulated laboratory dataset and the data
acquired from consecutive patients in the real-world clinical setting.
Discordant results between STANDARD M10 and Allplex were observed in
specimens with a Ct value >33 using the Allplex assay.
These findings that the limit of detection of RT-PCR is associated with
a viral load of the samples estimated by the Ct value are also reported
by previous researchers who evaluated the performance of rapid RT-PCR.
Jeong et al. found that the PPA of STANDARD M10 was 97.4% of the
conventional RT-PCR assays.9 However, the PPA was
decreased to 87.5% in samples with a Ct value of >30 for
the E gene, similar to that noted in the present study. Recent
studies compared well-known cartridge-based rapid RT-PCR assays, Xpert
Xpress SARS-CoV-2 (Xpert) and ID NOW COVID-19 (Abbott, IL, USA; ID NOW)
with the Roche Cobas SARS‐CoV‐2 (Roche Molecular Systems, NJ, USA) for
samples with low, medium, and high SARS‐CoV‐2 viral
concentrations.10,11 The two rapid RT-PCR assays
showed 100% positive agreement for medium and high viral
concentrations, defined as having a Ct value <30. However, for
low viral concentrations defined as a Ct value >30,
positive agreement for the Xpert was 97.1% (95% CI: 83.4–99.8%),
whereas it was 34.3% (95% CI: 19.7–52.2%) for the ID NOW
assay.11
Before the COVID-19 pandemic, the Korea Disease Control and Prevention
Agency prepared a laboratory diagnostic system in response to a
potential unknown disease outbreak.12 This system was
successfully applied for laboratory diagnosis based on developing and
implementing RT-PCR for the causative pathogen of COVID-19 in the very
early phase of the COVID-19 pandemic in Korea. However, there was no
reliable domestic rapid RT-PCR method in Korea, and thus, diagnosis
depended on imported rapid-RT-PCR methods such as Xpert. The Xpert
method yields reliable results, but it has issues with high prices and
substantial undersupply of reagents in Korea. STANDARD M10 is a method
similar to Xpert, a completely automated cartridge-based point-of-care
testing method but less expensive than Xpert and in potentially
sufficient supply. After the introduction of STANDARD M10, the emergency
healthcare system of Korea could manage the Omicron surge as it can
serve as a reliable method in the real-world setting.
This is the first study including consecutive data collection from a
large patient cohort for clinical evaluation of STANDARD M10 in an
emergency department during the Omicron surge. However, several
limitations must be considered. First, because the study was performed
during the Omicron surge, the performance of detecting other variants of
concern could not be evaluated. Second, analytical performance was not
evaluated. Third, specimens used for STANDARD M10 and Allplex in the
initial test were different. Fourth, although retesting was performed
with the same specimen for specimens showing discordant results,
potential specimen effect could remain. Fifth, the ratio of patients
with severe medical conditions (KTAS levels 1 and 2 and a portion of
KTAS level 3) is lesser in this study than the real-word ratio. Because
the patient groups were indicated for the Xpert assay by the Korea
health insurance system, these patients underwent Xpert instead of
STANDARD M10. Thus, KTAS level 1–3 patients may be underrepresented in
this study.
In conclusion, the STANDARD M10 SARS-CoV-2 rapid RT-PCR assay showed
reliable clinical performance compared with the conventional RT-PCR
using Allplex SARS-CoV-2 in an emergency department. STANDARD M10 can be
a useful method for emergency healthcare because of its advantage of
cartridge-based fully automated system and short reporting time for
rapidly detecting SARS-CoV-2 compared with conventional RT-PCR. The
diversity of rapid-RT-PCR systems may also be useful to solve problems
associated with an imbalance of resources of rapid RT-PCR technology in
the world.