Review Related Literature

(Swab & Rapid Test)

According to BMJ (2020), a systematic review of the accuracy of covid-19 tests

reported false negative rates of between 2% and 29% (equating to sensitivity of 71-
98%), based on negative RT-PCR tests which were positive on repeat testing. The use
of repeat RT-PCR testing as gold standard is likely to underestimate the true rate of
false negatives, as not all patients in the included studies received repeat testing and
those with clinically diagnosed covid-19 were not considered as actually having covid-
19.
Accuracy of viral RNA swabs in clinical practice varies depending on the site and
quality of sampling. In one study, sensitivity of RT-PCR in 205 patients varied, at 93%
for broncho-alveolar lavage, 72% for sputum, 63% for nasal swabs, and only 32% for
throat swabs. Accuracy is also likely to vary depending on stage of disease8 and
degree of viral multiplication or clearance. Higher sensitivities are reported depending
on which gene targets are used, and whether multiple gene tests are used in
combination. Reported accuracies are much higher for in vitro studies, which measure
performance of primers using coronavirus cell culture in carefully controlled conditions.

The lack of a clear-cut “gold-standard” is a challenge for evaluating covid-19

tests; pragmatically, clinical adjudication may be the best available “gold standard,”
based on repeat swabs, history, and contact with patients known to have covid-19,
chest radiographs, and computed tomography scans. Inevitably this introduces some
incorporation bias, where the test being evaluated forms part of the reference standard,
and this would tend to inflate the measured sensitivity of these tests. Disease
prevalence can also affect estimates of accuracy: tests developed and evaluated in
populations with high prevalence (eg, secondary care) may have lower sensitivity when
applied in a lower prevalence setting (eg, primary care).

One community based study of 4653 close contacts of patients with covid-19
tested RT-PCR throat swabs every 48 hours during a 14 day quarantine period. Of 129
eventually diagnosed with covid-19 by RT-PCR, 92 (71.3%) had a positive test on the
first throat swab, equating to a sensitivity of 71% in this lower prevalence, community
setting.

Further evidence and independent validation of covid-19 tests are needed. As

current studies show marked variation and are likely to overestimate sensitivity, we will
use the lower end of current estimates from systematic reviews, with the approximate
numbers of 70% for sensitivity and 95% for specificity for illustrative purposes.

Reference:

BMJ (2020). Interpreting a covid-19 test result. Retrieved on September 23, 2020, from
https://www.bmj.com/content/369/bmj.m1808.long
 One study suggested that viral RNA levels are higher and RNA is more
frequently detected in nasal specimens as compared to oral specimens, however this
finding was based on a small number of nasal swabs tested. A COVID-19 investigation
team in the US comparing 117 pairs of nasopharyngeal and oropharyngeal specimens
from 12 patients simultaneously, found that 32 pairs were discordant with one test
positive and the other negative: the nasopharyngeal specimen tested positive in 66% of
those pairs compared with 34% for the oropharyngeal specimen. Another study did not
show higher viral RNA levels in nasopharyngeal compared with oropharyngeal
specimens.  

A meta-analysis of saliva testing studies found 91% (95%CI = 80%-99%)

sensitivity for saliva tests and 98% (95%CI 89%-100%) sensitivity for nasopharyngeal
swab tests in previously confirmed COVID-19 infected patients, with moderate
heterogeneity among studies. Another study showed that saliva was the most
appropriate sample for diagnosis of SARS-CoV-2. Saliva offers a non-invasive
specimen that can also be considered for self-sampling. In a situation where a
nasopharyngeal or other above mentioned specimen is not acceptable, saliva could be
considered as an alternative specimen. The combination of
nasopharyngeal/oropharyngeal swab samples proved more sensitive for diagnosis of
SARS-CoV-2 compared to nasopharyngeal swab only in three different studies.

Antibody tests currently have limited diagnostic use. They can be used as a
complement to the virus detection tests for patients presenting late after symptoms
onset to healthcare facilities and where virus detection tests are negative despite strong
indications of infection. In addition, they can potentially be used for informing the
decision on discharge of patients who recovered from SARS-CoV-2 infection but
remain RNA-positive by RT-PCR for a long time after symptoms have subsided. The
degree of protective immunity conferred by or correlated with the antibodies detected in
subjects with past SARS-CoV-2 infection is still under investigation. Once this is
clarified, such antibody tests could be, together with the direct virus detection, an
essential tool in de-escalation strategies. Currently antibody tests are used for sero-
epidemiological surveys and studies.

When rapid antigen tests are well-validated, they may be considered for the
rapid diagnosis of infected patients. However, these tests tend to have lower sensitivity
than RT-PCR, and therefore a negative rapid test may not be able to rule out infection.
They may be useful during an ongoing outbreak, when timely access to sensitive
molecular testing is unavailable, but a negative result should be interpreted by a
healthcare professional with caution and based on clinical judgement.