The high transmissibility of the associated SARS-CoV-2 virus and the widespread prevalence of the associated COVID-19 have called for the development and utilization of testing methods, as well as the deployment of rapid test kits for proper diagnosis, delivery of appropriate medical response, and population surveillance.
Note that the success of some countries, such as in the experience of mainland China and the response of Taiwan, in managing the COVID-19 crisis in their jurisdictions has been particularly attributed in the availability of testing.
Background on COVID-19 Testing: Methods for Detecting SARS-CoV-2 and Diagnosing COVID-19
Three methods have been developed and utilized for COVID-19 testing, specifically for detecting the specific coronavirus and/or diagnosing the resulting disease. The first is diagnosis through a molecular method that detects viral presence. Based on Real-Time Reverse Transcription Polymerase Chain Reaction or rRT-PCR, it involves taking samples and detecting the genetic material of SARS-CoV-2.
On the other hand, the second is diagnosis through serological method, especially through the detection of antibodies produced by the immune system in response to infection. It involves taking a single specimen of blood and performing assays in central laboratories or CLT or point-of-care testing or PoCT facilities.
The third and least used method for diagnosing COVID-19 is detection trough medical imaging, specifically using either chest radiographs x-rays or chest computed tomography or CT scans. Several studies proposed the use of artificial intelligence in reading chest scans. This includes the COVID-Net neural network developed by researchers from the University of Waterloo and the Canada-based technology company DarwinAI.
Another emerging method involves the use of the gene-editing technique called CRISPR. It banks on using the ability of CRISPR to recognize and cut specific genetic sequences, as well as the addition of a reporter molecule to the reaction. The result is a faster extraction and identification of the viral genetic material.
Both the United States Centers for Disease Control and Prevention or CDC and the American College of Radiology recommend not to use chest scans for initial screening or as a first-line test to diagnose COVID-19. There is a consensus recommending the use of the molecular method through rRT-PCR for a more accurate COVID-19 testing.
Molecular Method vs. Serological Method of SARS-CoV-2 Detection: Comparing RT-PCR Test Kits and Antibody Test Kits
Remember that the molecular method through rRT-PCR involves detecting the viral particles of SARS-CoV-2. The process consists of collecting respiratory samples through a nasopharyngeal swab or sputum collection, extracting the viral genetic material from the sample if it is present, and performing a combination of reversing RNA into DNA and the amplification of specific DNA targets to measure the amount of specific RNA.
COVID-19 testing based on PCR essentially locates a coronavirus gene sequence and creates multiple copies that can be detected easily. Note that coronaviruses such as SARS-CoV-2 are RNA viruses. Nevertheless, depending on the manufacturer, different PCR test kits target different coronavirus genes. The principles are essentially the same but the genetic targets vary.
For example, the widely used kits, such as those recommended by the World Health Organization, involve detecting the E gene of the virus, which codes for the envelope surrounding the viral shells, and the gene for the enzyme RNA-dependent RNA polymerase. Meanwhile, the kits approved and endorsed by CDC target regions on the N gene that codes for the protein that makes the nucleocapsid of the coronavirus.
One of the advantages of using rRT-PCR is that it is highly sensitive and specific. Furthermore, depending on the kits and laboratory capacity, it can deliver a reliable diagnostic as fast as six to eight hours. It is worth stressing the fact that health authorities from around the world recommend the use of this testing method because it can diagnose both symptomatic and asymptomatic cases of COVID-19.
However, a critical disadvantage of the molecular method is that it can only be used when there is still a viral presence in the human body, thus rendering it useless for detecting, tracking, and studying previous exposures of individuals and the entire population. It is for this reason that the serological method based on antibody testing becomes essential.
It is first necessary to note that antibody test kits should be used for diagnosing COVID-19 because results cannot pinpoint whether an individual still has the SARS-CoV-2 virus or the detected antibodies are mere indicators of a previous infection. There have been several cases of people testing positive for the virus for the second time despite testing negative via PCR.
Remember that the immune system produces specific antibodies in response to an infection. A specific kit for COVID-19 testing detects the presence of antibodies produced as a response to SARS-CoV-2 infection. However, these antibodies are usually detectable 14 days after the onset of COVID-19 symptoms, and they remain in the body even if the individual has already recovered from the disease and there is no virus present in the system.
Understanding COVID-19 Progression: The Importance of Using rRT-PCR Testing and Antibody Testing
Both the molecular method via rRT-PCR testing and serological method via antibody testing are essential in understanding, managing, and eliminating the COVID-19 pandemic. For starters, PCR testing is for determining current infection with SARS-CoV-2, while antibody testing is for previous exposure to the same virus.
The value of PCR testing is that it informs individuals about their health status, as well as healthcare providers about the medical response they need to provide. It also informs the patients about the actions they need to undertake to prevent transmission. On the other hand, antibody testing can help in facilitating contact tracing and surveillance, as well as in identifying potential immunity for SARS-CoV-2 for the development of new therapies.
An article published by The Guardian also explained the importance of utilizing and maximizing the two methods for COVID-19 testing to predict the spread and progression of the pandemic. There are two reasons according to scientists. First, it is imperative to understand where and when new cases are appearing through testing. Second, it is also critical to identify previously infected individuals, including those asymptomatic cases, for scientists to understand the progression of the pandemic over the coming months.
The first reason depends on the availability and accessibility of rRT-PCR test kits. Of course, accurately determining the presence of SARS-CoV-2 depends on the quality of samples collected by healthcare workers. Other factors that limit testing via PCR are the availability of kits, the capacity of laboratories, and the geographic distribution of testing areas.
Meanwhile, the second reason requires the widespread use of antibody test kits. Researchers believe that performing serological testing is not only beneficial in determining the extent of the pandemic and the number of infection rates. More specifically, it would provide scientists a clearer idea of how the disease behaving while also providing a possible solution for the development of therapies based on established immunity to the virus.
FURTHER READINGS AND REFERENCES
- American College of Radiology. 2020. “ACR Recommendations for the Use of Chest Radiography and Computed Tomography for Suspected COVID-19 Infection.” American College of Radiology. Available online
- Bai, H. X., Hsieh, B., Xiong, Z., Halsey, K., Choi, J. W., Tran, T. M. L., Pan, I., Shi, L-B., Wang, D-C., Mei, J., Jiang, X-L., Zeng, Q-H., Egglin, T. K., Hu, P-F., Agarwal, S., Xie, F., Li, S., Healey, T., Atalay, M. K., and Liao, W-H. 2020. “Performance of Radiologists in Differentiating COVID-19 from Viral Pneumonia on Chest CT. Radiology. 200823. DOI: 1148/radiol.2020200823
- Centers for Disease Control and Prevention. 2020. CDC 2019-Novel Coronavirus (2019-nCOV) Real-Time RT-PCR Diagnostic Panel. Division of Viral Diseases, Centers for Disease Control and Prevention. Available via PDF.
- Centers for Disease Control and Prevention. 2020. “Testing for COVID-19.” Coronavirus Disease 2019. Centers for Disease Control and Prevention. Available online
- Heaven, W. D. 2020. “A Neutral Network Can Help Spot COVID-19 in Chest X-Rays.” MIT Technology Review. Available online
- McKie, R. 2020, March 29. “The Two Tests That Will Help to Predict Spread of COVID-19.” The Guardian. Available online
- Patel, R., Babady, E., Theel, E. S., Storch, G. A., Pinsky, B. A., St. George, K., Smith, T. C., and Bertuzzi, S. 2020). Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS–CoV-2/COVID-19. mBio. 11(2). DOI: 1128/mbio.00722-20
- Subbaraman, N. 2020. “Coronavirus Tests: Researchers Chase New Diagnostics to Fight the Pandemic.” Nature. DOI: 1038/d41586-020-00827-6