Scientific Methods for Testing COVID-19
The real danger of the novel coronavirus disease 2019 (COVID-19 or SARS-CoV-2) does not come from its lethality of 3.4% but its ability to rapidly spread through the population and overwhelm hospitals, just like what happened in Wuhan, Tehran and northern Italy. All hell breaks loose once hospitals are overrun by coronavirus patients, quickly exhausting healthcare workers and essential medical supplies.
Even in the worst-imaginable scenario where 100% of the world population eventually become infected by COVID-19, slowing down the spread of the coronavirus must remain the number one priority of all governments. By slowing down the spread and flattening the curve of newly infected cases, we protect our society’s first line of defense against the coronavirus, the healthcare workers and hospitals.
Methods for slowing down the spread can range from basic hygiene like washing your hands to travel restriction and city lockdown. One essential method is to quickly identify and isolate the infected before the virus spreads to others. Here, we review and compare different scientific methods for testing COVID-19, namely (i) RT-PCR, (ii) IgG/IgM antibody immunoassay, (iii) a chest CT/X-ray scan and (iv) CRISPR diagnostics.
Note: the list below is by no means exhaustive. A more comprehensive list can be found here.
1. RT-PCR
Reverse transcription polymerase chain reaction (RT-PCR) takes RNA samples from upper respiratory tract (such as throat or nose swabs), generates complimentary DNA from the RNA (with RT) and then makes millions of DNA’s copies in a laboratory (with PCR). This technique allows scientists to accurately detect specific RNA of COVID-19 virus from a small amount of samples. RT-PCR can distinguish COVID-19 from other types of virus and even from its close cousin, SARS. RT-PCR home testing kits could be distributed to people at home to collect samples that are then sent back to laboratories.
Advantages: RT-PCR is a specific test for COVID-19 as it reads the genetic material of the virus. It is currently the standard technique.
Disadvantages: RT-PCR tests take up to 5 hours of processing time in laboratories. The results usually become available 1–2 days after sample collections and could take up to one week during the outbreak due to high demand.
2. Antibody Test
Once someone is infected by COVID-19, immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies are produced as part of their immune responses. These antibodies can be detected by a serology test with lateral flow immunoassays. Several companies, such as SureScreen, BioMedomics and Healgen, have developed home testing kits for COVID-19 IgG/IgM antibodies that take finger-prick blood samples. If a test is positive, colored bands will be visible on the test kit.
Advantages: Antibody tests are cheap and fast. The tests only take 10–15 minutes and allow for rapid screening of COVID-19. The tests can be processed at home or at local clinics.
Disadvantages: Antibodies only become detectable a few days after infection. Moreover, patients who are immunocompromised may not produced a detectable amount of IgG/IgM antibodies. Antibody tests are also non-specific and result in higher false positives than RT-PCR.
3. Chest scan
A large proportion of coronavirus patients develop pneumonia. Although most cases are mild, respiratory failure caused by severe pneumonia is the leading cause of COVID-19 mortalities. Detecting early development of pneumonia by chest scan, thus, provides an important clue to detect early-stage COVID-19 infection. Some studies suggest that a chest CT scan is even a more sensitive test for COVID-19 than the standard RT-PCR test. Chest X-ray is also common for detecting COVID-19 pneumonia. Although it provides chest images of lower quality than CT scan, X-ray is more commonly available in hospitals and local clinics.
Advantages: A chest CT scan is more sensitive at detecting early-stage infection of COVID-19 than RT-PCR. It is very useful for tracking suspected patients and checking the progression of the disease.
Disadvantages: Although a chest scan is more sensitive than RT-PCR, it has lower specificity (as it is a non-specific test) and cannot distinguish COVID-19 pneumonia from other types of pneumonia. Hence, a chest scan is currently not recommended for initial screening.(Note: Alibaba has recently developed CT Image Analytics for COVID-19.) Moreover, scanning equipments could become contaminated and help spread the disease. A chest scan is also not applicable for home testing due to the size and cost of the equipments.
4. CRISPR Diagnostics
CRISPR is mostly known as a genome editing technique with the ability to precisely find and cut DNA at a specific location. However, CRISPR can also be used as a search engine for a specific RNA sequence — like Google for biology. Currently, two research groups independently developed similar protocols, called SHERLOCK by Broad Institute and DETECTR by Mammoth Biosciences. These techniques can be used to identify coronavirus in samples from upper respiratory tract (e.g. a nasal or oral swab).
Advantages: CRISPR diagnostics is also specific as it reads genetic material of the virus. It also uses the same types of samples as RT-PCR. The test results become available within one hour (30 minutes for DETECTR and 60 minutes for SHERLOCK).
Disadvantages: CRISPR diagnostics for COVID-19 are currently under research and have not yet been properly tested on real patients (as of March 2020). CRISPR diagnostics potentially result in higher false positives than RT-PCR.
In most countries, suspected coronavirus patients are still required to get tested (with RT-PCR) at hospitals. As a result, the virus could be unnecessarily spread at the hospitals and during the transits. Therefore, it is important that home testing kits are mass-produced and then distributed at low cost to the public.
In the near future, RT-PCR will remain the irreplaceable standard method for testing COVID-19. However, RT-PCR alone is insufficient for testing every suspected case as the demand rises. Home testing kits based on IgG and IgM antibody testing are great complements to RT-PCR, providing rapid initial screening, whereas CRISPR diagnostics is an exciting new development. A chest CT scan is also a powerful tool to help identify the infections at the earliest stage although it must still be used in combination with other techniques.
References:
COVID-19 Diagnostics: J. C.-H. Yap, et al. COVID-19 Science Report: Diagnostics, ScholarBank@NUS Repository (2020).
CRISPR diagnostics (SHERLOCK): F. Zhang et al., A protocol for detection of COVID-19 using CRISPR diagnostics, Broad Institute, v.20200311 (2020).
CRISPR diagnostics (DETECTR): J. P. Broughton, A protocol for rapid detection of the 2019 novel coronavirus SARS-CoV-2 using CRISPR diagnostics: SARS-CoV-2 DETECTR, Mammoth Biosciences, v3 (2020).
Chest CT scan: Y. Fang et al., Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR, Radiology (2020).
