More Rapid Antigen Tests, Less RT-PCR Ones: Why We Need To Rethink Covid-19 Testing

From the beginning of the Covid-19 pandemic, real-time polymerase chain reaction (RT-PCR) test has been hailed by the scientific community and experts as the gold-standard test to detect the SARS-CoV2 virus.

The governments across the world have understood it to be a front-line tool to curb virus outbreaks by testing, tracing and quarantining the infected and their contacts.

The quantitative RT-PCR tests have been throwing up tens of thousands of positives per day and have overwhelmed some countries' healthcare capacities during their peak of the outbreak.

For months, public health commentators have been criticising the governments for not ramping up testing fast enough, thereby prolonging the fight against the pandemic.

Come to think of it, testing is the first step to combat the coronavirus. The steps that follow — tracing of infected, quarantining close contacts, lockdowns, defining containment zones, et cetera — all depend on the number of positives.

And since RT-PCR has been the frontline and gold-standard test, it has played the most important role in deciding the actions of governments throughout the world.

But now, some experts are highlighting some blind spots of the RT-PCR, which basically show that everyone might have got their virus fighting method wrong.

This means that the pain and suffering that millions have suffered due to lockdowns based on wrong strategy could’ve been avoided.

So what went wrong?

Some experts are now pointing out that the RT-PCR test for the new coronavirus gives a simple 'yes' or 'no' answer (whether the virus is present or not) and is too sensitive due to higher cycle threshold (Ct) values it is set for.

When a sample enters the test, the machine is basically looking for virus RNA, but it has to be amplified to be seen.

The Ct is the number of cycles it takes to detect the virus. Thus, if the Ct value is high, then it means that there was less virus in the sample. And if the machine detects the virus in fewer cycles, then the virus was high.

In RT-PCR tests for the novel coronavirus, Ct has been set very high. In the United States, it’s 37 or 40.

In India, ICMR has set it at 40. So, the test will go through 40 cycles to detect the virus. Experts are now saying that this is too high.

“Tests with thresholds so high may detect not just live virus but also genetic fragments, leftovers from infection that pose no particular risk — akin to finding a hair in a room long after a person has left,“ Dr. Michael Mina, an epidemiologist at the Harvard T.H. Chan School of Public Health, told The New York Times.

He says that “he would set the figure at 30, or even less.”

This doesn’t mean that these 80-90 per cent people aren’t infected. It simply means that their viral load is too low to matter. They aren’t contagious at the time of the test and, therefore, do not need quarantining as their chance of infecting others is almost non-existent.

The New York Times trolled through data of some labs in Massachusetts, New York and Nevada and found that if the Ct for RT-PCR tests was set at 30 rather than the current 40, then 80-90 per cent of the people who tested positive would’ve tested negative.

One can imagine the difference it makes to policymaking, which is being driven by daily positives and growth of infections.

Apart from lowering the Ct for RT-PCR, experts are recommending rapid antigen tests, which are less sensitive, meaning that they return positive for only those who have high viral loads and miss out on those who are most likely not contagious.

India did the wise thing by shifting focus from RT-PCR tests to rapid antigen tests in June.

Many states are now carrying out more antigen tests than the RT-PCR ones.

Some have criticised the governments for this, as those who turned 'negative' in the antigen test showed 'positive' in the RT-PCR one.

But now we know that such people have too little viral load to be accounted for, from the public health perspective.

One hopes that all the governments invest heavily in more and more rapid antigen tests, even if they are less sensitive.

That’s not a bad thing. What matters is they are quick, easy to administer, cost little, don’t require highly trained staff to carry them out and can be taken at frequent intervals.

The argument is thus not to decrease testing but to increase it, however, with a more useful method.

These (rapid antigen tests) might not catch every last one of the transmitting people, but they sure will catch the most transmissible people, including the superspreaders and that alone would drive epidemics practically to zero, says Dr Mina.

Turns out the RT-PCR test may be gold-standard in detecting the virus at an individual level, but as far as fighting the pandemic is concerned, rapid antigen tests may be the new gold standard and should now be the frontline tool in controlling the outbreaks.