Testing for COVID-19: The Road Ahead
By Dr. Aarthi Kannan
In early 2020, as the SARS-nCOV-2 virus spread rampantly affecting millions of lives across the planet whilst severely straining healthcare systems worldwide, the diagnostic industry was met with several new challenges. In addition to the shortage of raw materials required to ramp up testing, the need to develop quick, reliable and easy means of testing came to the forefront. The importance of decentralizing COVID-19 testing to avoid burdening already burned-out healthcare systems and labs also became evident very early on in the pandemic. In this article, we explore the inherent strengths and weaknesses of the common existing testing modalities for COVID-19, the challenges met in fulfilling the testing needs of ever-increasing patients and what is in the pipeline for easily accessible COVID-19 testing. Mumbai-based microbiologist Dr. Anjali Shetty speaks to Dr. Aarthi Kannan.
The two most widely performed tests at present in India are the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and the Rapid Antigen Test (RAT).
How the RT-PCR and RAT compare with each other
RTPCR
“The RT-PCR test for COVID-19 has a high sensitivity of 87% and a very high specificity of 98%. The high positive predictive value and specificity of RT-PCR make the probability of a false-positive test very low unless the sample is mixed-up or wrongly labelled. It is considered the gold-standard for COVID-19 testing. Running the test is time-consuming. It can take up to six hours to run with a manual extraction system. The availability of an automated extraction system would revolutionize the testing process in terms of simplicity and time taken. Sometimes, despite strong suspicion of clinical picture of COVID-19 and high CT scan suspicion of COVID-19 infection, the test can be negative because of poor sample collection technique, because the sensitivity is not 100% or presence of certain inhibitors in the master mix while running the test. If RT-PCR is negative but clinical suspicion for COVID-19 is high such as a symptomatic patient with history of contact with a COVID positive individual or the Computed Tomography (CT) scan showing a CORADS score of 5 and above, then you should repeat the RT-PCR. The nasopharyngeal swab is the best and more reliable than a nasal swab alone.”
The RT-PCR is not without challenges, though. The process that goes behind running the test after collecting the sample looks invisible, but it is not. A whole new world exists in testing labs where laboratory personnel put their safety and lives at risk to run these tests. Dr. Shetty explains that running the PCR, wearing the requisite protection to conduct the test, having availability of lab personnel with the requisite technical skill to run the test are more difficult than we imagine.
“Training the staff and motivating them is often challenging. This challenge becomes more pronounced during lockdowns with hinderances in transportation. In addition to difficulty in accessing workplaces, lab personnel also meet obstacles in fulfilling their chores and domestic needs during a lockdown. This is tough especially when they have to work round the clock.”
RAT
The Rapid Antigen test (RAT) is less cumbersome and offloads the burden of our dependence on RT-PCR. As the name suggests, the RAT is a rapid test requiring far less technical expertise than the RT-PCR with results available within thirty minutes of collecting the sample.
“The RAT however, falls short in that its sensitivity is poor between 50 to 80%. It picks up those who are very infectious but may miss those who are not infectious.”
Effective alternatives to the RT-PCR and lab-based Rapid Antigen Test
The conventional RT-PCR and RAT tests require us to step outside the comfort of our home and undergo testing in a laboratory, designated testing center or a hospital.
The Abbott ID now, which uses isothermal amplification technology, could be a very good alternative which can be performed in urgent care clinics or smaller healthcare settings as a point of care test. This test is a molecular RNA amplification technique that provides results in thirty minutes. The cycle threshold of this test is slightly lower than that of the conventional RT-PCR.
“It picks up people who are more infectious. Even though its sensitivity is slightly lower than that of a conventional RT-PCR, it is still highly sensitive. I would say that the conventional RT-PCR is even possibly a little too sensitive.”
The CRISPR (clustered regularly interspaced short palindromic repeats) technology can also be developed into a lateral flow assay which would make diagnostics a lot easier.
The Mylab home-based rapid antigen test has a sensitivity is 50 to 80%. “It is important to understand that this test is meant for symptomatic patients only or contacts of a COVID-19 positive patient. This test does not serve well to screen asymptomatic patients whose pre-test probability of COVID-19 is low. A positive is a true positive but a negative test always needs to be confirmed with an RT-PCR.”
What makes this test revolutionary is that it is home-based, relatively inexpensive, simple to use and just requires the kit and a downloadable app for the phone. It involves a nasal swab collection followed by placing the sample in the extraction media provided in the kit. The picture of the test kit then needs to be uploaded onto the app and the test will be resulted in 15 minutes through the app. Since it is integrated with the ICMR (Indian Council of Medical Research) COVID-19 setup, patients will automatically be logged in there as positive or negative onto their system. This test kit costs Rs. 250. The caveat to this test is that one must not be falsely reassured if it results as negative. A negative test must always be confirmed with an RT-PCR.
The road ahead for us in regards to COVID-19 testing is all but clear. However, the advent of new technologies such as isothermal amplification-based RNA testing, CRISPR, home based antigen testing, all carry the hope for an easier diagnostic future. The hope is after all, that one day, COVID-19 evolves into an illness as mild as a common cold so that we wouldn’t need to test for it at all.