New Delhi: Quicker and cheaper but less reliable than the “gold standard” RT-PCR, rapid antigen tests (RAT) have come a long way since they were introduced for Covid-19 testing around five months ago. They now form an important cog in Covid management as part of the Swiss Cheese Model, a strategy that underlines putting up a multi-pronged defence against the disease instead of taking piecemeal measures.
There have been concerns about the tests as they are known to be prone to false negatives, but newer variants seem to be addressing those gaps.
In a preprint (non-peer-reviewed study) published earlier this month by Spanish researchers, a new rapid antigen test (RAT) by American pharma firm Abbott was found to have a sensitivity of 79 to 80 per cent. This means that around 20 per cent of Covid patients are likely to get a false negative diagnosis from the test.
The figure of 79-80 per cent, the researchers said, depended on whether the test was done in an adult or a child, and also at what stage of the infection it was carried out. The sensitivity was higher in adults and in people who had been infected for less than five days.
The specificity of antigen tests was never much in question. This study found a specificity of 100 per cent, which re-established that a positive diagnosis from RAT almost definitely means that the virus (antigen) is present.
The researchers also claimed that of the 412 patients tested using both RT-PCR and Abbott’s PanbioTM Covid-19 Ag Rapid Test Device, only 11 yielded divergent diagnoses with the two different tests.
As things stand, globally, the use of rapid antigen tests is only advised under certain conditions to avoid getting an incomplete picture of the pandemic’s prevalence, with the World Health Organization (WHO) advising the use of tests with a sensitivity of not below 80 per cent.
In India, however, the test being used has a far lower sensitivity, leading to some concerns about its scale of deployment in the country.
The Swiss Cheese Model
In the battle against Covid-19, Rapid Antigen Tests are considered a part of the ‘Swiss Cheese Model’, a popular term among healthcare professionals (and other fields) to describe a multi-pronged strategy to tackle a certain threat.
To understand what the model depicts, one needs to picture slices of Swiss cheese, which have holes in them. If the slices be seen as different measures to handle Covid-19 — social distancing, mask use, hand hygiene and use of rapid tests — the holes would represent the gaps in each measure when employed alone.
However, if all the measures are taken together — and the different slices of cheese held together — the gaps in each might be compensated by the remaining safety tactics.
— Dr. Jennifer Kwan (@jkwan_md) October 6, 2020
A slightly updated version devised by Australian virologist Dr Ian M. Mackay adds three more layers — ventilation, contact tracing and surface cleaning.
Slightly updated to version 1.3 pic.twitter.com/r5o8zv6fZr
— ɪᴀɴ ᴍ. ᴍᴀᴄᴋᴀʏ, ᴘʜᴅ 🦠🤧🧬🥼🦟🧻 (@MackayIM) October 12, 2020
The WHO has laid down certain norms for the use of rapid antigen tests.
“Use of Ag-RDTs (rapid diagnostic test) can be considered in countries or areas that are experiencing widespread community transmission, where the health system may be over-burdened and where it may not be possible to test all or any suspect cases by NAAT [RT-PCR is a type of NAAT test],” the UN health agency said in an interim guidance issued on 11 September.
“As with all diagnostic tests, but especially those with sub-optimal sensitivity and/or specificity, to correctly interpret and act on the results of the RDT, the prevalence of disease (according to the reference standard) must be estimated based on surveillance, since this determines the positive and negative predictive values.”
RAT, it added, should be used to “respond to suspected outbreaks of Covid-19 in remote settings, institutions and semi-closed communities where NAAT is not immediately available”.
“Positive Ag-RDT results from multiple suspects is highly suggestive of a Covid-19 outbreak and would allow for early implementation of infection control measures. Where possible, all samples giving positive Ag-RDT results (or at least a subset) should be transported to laboratories with NAAT capability for confirmatory testing,” it said.
At minimum, the guidelines state, Ag-RDTs would need a sensitivity of 80 per cent or more and specificity between 97 and 100 per cent.
RAT in India
India currently uses tests with a specificity of 99.3-100 per cent and a sensitivity of 50.6 per cent to 84 per cent.
With the exception of Tamil Nadu, most states are banking heavily on these rapid tests to contain the pandemic.
On Monday, the Union Health Ministry said about 49 per cent of all Covid-19 tests done in India were rapid antigen tests — against 46 per cent RT-PCR. In Bihar, 88 per cent of all tests done so far have been RAT.
In Kerala, just about 15 per cent of the tests are RT-PCR. In Delhi, meanwhile, about twice as many antigen tests are conducted every day as RT-PCR tests, a figure that has earned the government judicial rap.
The Indian government has sought to defend the heavy reliance of states like Bihar on RAT. “It can be argued that they are doing too many antigen tests but we have advised all states to ensure symptomatic negatives are tested with RT-PCR. We do not want an infected person to go undetected,” said Union Health Secretary Rajesh Bhushan.
‘Problems with the quality of the tests’
The primary fear among some experts about the wide use of RAT for Covid testing is the fact that false negatives may aid further transmission.
According to virologist Dr Shaheed Jameel, the problem is not so much “with antigen tests per se as with the quality of the tests that India is using currently”.
“ICMR’s own tests (on the kit used in India) show just 50-60 per cent sensitivity which means 40-50 of every 100 infections are missed. There is no doubt that India is overusing antigen tests,” he said. “There is a time and place to do them but it cannot be used to survey populations simply because the sensitivity is very poor. Also, different states are using the tests to different extent, there are variations by areas. It is very difficult to keep track of trends like this.”
Dr Jameel clarified that “all antigen tests are not bad”, adding that there are some very good antigen tests available. “For example there is one for dengue that detects the infection on day 1,” he said.
However, others point out that even “gold standard” RT-PCR can miss infections, only to a lesser extent than RAT.
According to Dr K. Srinath Reddy, president of the Public Health Foundation of India (PHFI) and member of India’s Covid-19 task force, even the RT-PCR test can miss 30-40 per cent of cases if the swab is taken too early in the infection or the collection technique is not perfect.
Reached for a comment on the concerns surrounding large-scale rapid antigen testing, the ICMR spokesperson said its use “eases up testing and also improves access and availability specially in areas where establishing RT-PCR facility becomes a challenge”. “Besides, RAT also tremendously improves the turnaround time of testing,” the spokesperson added.
The spokesperson also said the Ministry of Health and Family Welfare and the ICMR “are continuously reviewing the data on follow-up RT-PCR after a negative RAT result in symptomatic patients”.
“The data varies from state to state. However, by repeated follow-up through virtual interactions/letters, the follow-up RT PCR tests in symptomatic RAT negatives is now steadily increasing…” the spokesperson added.
Asked whether there are plans to bring in tests with better sensitivity, the spokesperson said the “availability of rapid antigen tests is not a limitation now”. “ICMR has so far approved 11 RAT test kits. More than a dozen RDTs are also under validation. Many of them are indigenous. Additionally, multiple choices are also available,” the spokesperson added. No reply was offered to a question on whether such large-scale use of antigen tests suggests India is in community transmission.
When asked why only symptomatic people are expected to go for an RT-PCR confirmation after a negative RAT test, even though the government itself estimates that 80 per cent of India’s Covid patients are asymptomatic, the spokesperson noted that many asymptomatic patients develop symptoms within a couple of days of the test.
“The ICMR advisory states that once an asymptomatic individual is tested and turns out to be RAT negative, he/she should be re-tested if the individual turns symptomatic. The report of 80 per cent Covid-positive asymptomatic cases is based on their being asymptomatic at the time of testing. However, many such individuals eventually become symptomatic in a day or two,” the spokesperson said. “Besides, the sensitivity of new RATs is also improving and so is their capacity for detecting Covid-19 cases.”