Deepak G. Tripathi
A midst rising cases of COVID-19 globally, there is an urgent need to unlock the economies so that governmental and personal incomes can be restored hopefully to pre-COVID levels as soon as possible. A balance needs to be achieved to protect health and economic well-being. Current methods deployed for capacity-building at hospitals and keeping the population safe have outlived their utility. There is a need to confront the new challenges with a new strategy during Unlock 2.0, especially by exponentially increasing the current volumes of testing.
RT-PCR tests that detect the viral RNA of SARS-CoV-2 are extremely sensitive tests, and have emerged as the mainstay of disease diagnosis during the pandemic. However, they come with severe limitations: high cost, requirement of labs, lab equipment, and expertise to run the test correctly. Expansion of testing based on this technology alone has posed technological, economical and logistical challenges, especially to mid-income countries. Anecdotally, there is a significantly high rate of false negative results of about 35% due to poor sample collection techniques of the nasal and oral swab. Experience abroad shows that only one out of three swabs taken on three sequential days is positive. The limit of detection of various tests differ by a factor of 100 times between manufacturers. Nearing the onset of symptoms of the disease, the RT-PCR test itself starts to lose sensitivity and reaches around 60% a week after onset of symptoms. Though a gold-standard, RT-PCR cannot claim a 100% performance in pandemic situations, especially in resource poor settings. False positive PCR results are not unknown too. A supplemental test to the RT-PCR is required to validate its findings.
Once a person is infected, from the day of appearance of symptoms, the patient starts to form anti-bodies to SARS-CoV-2. The anti-bodies are of the types, namely, IgA, IgM, and IgG, where the IgA appears by Day-7 of onset of symptoms, followed by IgM, around Day 10-14, and IgG, around Day 10-21. Since IgA anti-bodies appear first, and in higher concentrations, an anti-body test would not function efficiently if it only detects IgM and IgG as most countries have experienced during the pandemic. Total anti-body tests are available that can detect all three types of antibodies simultaneously, giving sensitivity from Day-7 of symptom onset.
It must be remembered clearly that infection will almost always produce an anti-body response. In RT-PCR positive asymptomatic cases, a rapid antibody test provides proof of seroconversion, and indirect evidence of infection. In sero-prevalence studies where, total antibody tests are performed on a random population, a positive test result indicates that the person was exposed to the virus at least a week earlier since antibodies appear after 7 days. One-week additional time in self-isolation, or home quarantine would suffice for the person to resume normal life, as, post-infection, the virus-shedding reportedly stops after Day-12 of the infection, and, immunity would have developed.
The role of anti-body as a protective tool is the basis of plasma-therapy and vaccination, towards which, there is a race amongst manufacturers around the world. The role of these anti-bodies as a diagnostic marker needs to be understood, explored, and used during the pandemic, as:
a) A companion test to the RT-PCR (b)a test for serodiagnosis of SARS CoV-2 infections (c)a means to conduct sero-prevalence surveys.
This will not only reduce the costs associated with SARS-CoV-2 testing, but, also, increase the number of tests that could be done in a day, and help cover larger populations in a short time to know their seroconversion status. As compared to a standard RT-PCR which takes about 24 hours from swab-collection to report, these tests can be performed in 20 minutes at the street-level without laboratory expertise or cold-storage requirements using finger prick blood!
The industry, doctors in clinics, private laboratories, dentists, corporate houses, airlines, and hospital staff are clamouring for the availability of such tests nationally, to reduce anxiety amongst employees and to know the sero-status of the unknown customer. A sensitive and specific rapid antibody-based test, when used appropriately can help open up our economies. Policy makers must make efforts in this direction so as to create an appropriate advisory for use of total antibody tests.
Lastly, RT PCR tests can only shut down economies whereas total antibody tests only can help it unlock!
The above article draws heavily from scientific literature published in internationally acclaimed medical journals/press. A sincere attempt has been made to accurately present simplified information for the benefit of readers.
(The author is President, Tulip Diagnostics Pvt. Ltd., an IVD Major, based at Goa, India.)