Figure 3. The possible viral entry and replication mechanism of SARS-CoV-2.
  1. Diagnosis and Pathogenesis of SARS-CoV-2
  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.