Figure 3. The possible viral entry and replication mechanism of
SARS-CoV-2.
- Diagnosis and Pathogenesis of SARS-CoV-2
- Diagnostic testing for COVID-19
Rapid and accurate diagnosis of COVID-19 is of considerable significance
for controlling outbreaks in the communities and hospitals (To et al.,
2020). Technologies such as polymerase chain reaction (PCR),
reverse-transcription polymerase chain reaction (RT-PCR), real-time
RT-PCR (rRT-PCR), and reverse transcription loop-mediated isothermal
amplification (RT-LAMP) have been leveraged as ideal diagnostic tests
for coronaviruses (Chan et al., 2015; Bhadra et al., 2015). To date, the
frontline reaction to the SARS-CoV-2 outbreak has been PCR testing. As
the gold standard for diagnosing the source of infection, PCR holds the
preponderance that the primers required for such assays can be generated
relatively quickly once the viral sequence is identified (Figure 4)
(Sheridan, 2020). Soon after the virus was identified, the first
quantitative RT-PCR assays to detect SARS-CoV2 were inaugurated and
distributed in January 2020 by WHO. Nevertheless, this test protocol was
complicated and high-priced, and is primarily applicable for large
centralized diagnostic laboratories. As for the diagnostic criteria
currently formulated by the China National Health Commission,
nasopharyngeal cancer and oropharyngeal swab tests have ripened into the
standard evaluation for the diagnosis of COVID-19 infection. So far,
three new RT-PCR tests targeting the RNA-dependent RNA polymerase
(RdRp)/helicase (Hel), nucleocapsid, and spike genes of SARS-CoV-2 had
been inaugurated, with extremely lower detection limit in vitro(Chan et al., 2020a). The SARS-CoV E gene detection was superior to the
RdRp gene test combined with the one-step RT-PCR system. The E gene PCR
was adequate for diagnosing SARS-CoV-2 infection, but the RdRp protocol
was endorsed to verify positive results (Corman et al., 2020).
Remarkably, a new FDA-authorized COVID-19 test using the Abbott ID NOW
diagnostics platform has been developed, which can produce results in
just 5 minutes, cutting down on wait times both in terms of getting
tested and receiving a diagnosis. As gene detection of SARS-CoV-2 might
provide false negative results, it can be complemented by antibody
detection, especially to better screen asymptomatic patients.
Clinically, for those who are recently suffering from fever, fatigue,
sore throat, cough, or dyspnea due to exposure, the diagnosis of
COVID-19 infection should be conducted with typical chest computerized
tomography (CT) characteristics regardless of negative RT-PCR outcomes
(Xie et al., 2020).
Most of the COVID-19 cases shared similar characteristics on CT images,
presenting bilateral distribution of patchy shadows and ground-glass
opacity, sometimes presenting a circular shape and peripheral lung
distribution (Kanne, 2020). Some of the data published from China showed
that in 21 primal chest CT scans, a large proportion of patients (86%)
developed frosted glass opacity, affecting more than one lung lobe
(71%) (bilateral involvement) (Chung et al., 2020). It is also worth
noting that lung cavitation, pleural effusions, discrete pulmonary
nodules, along with lymphadenopathy were absent (Chung et al., 2020). In
addition to imaging technology, a recent study displayed that the
Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter
unlocking) platform can be harnessed for diagnosis of SARS-CoV-2
(Broughton et al., 2020.). However, such a system needs to be further
verified in clinical tests. Overall, combined with immunochromatography,
colloidal gold, and other biotechnologies, associative detection
strategies have been progressed swiftly.