Omicron: Why a potential Covid-19 surge might need hybrid testing

Using a combination of RT-PCR tests with Rapid Antigen Tests (RAT) helps detect more cases faster during a surge in cases, in remote areas with little access to RT-PCRs and in Covid-19 hotspots

To quickly detect Covid-19 positive cases and slow the virus' spread in case of a possible surge due to the Omicron variant, India must increase its use of Rapid Antigen Tests (RAT, which take 30 minutes or less), in addition to the "gold standard" RT-PCR tests, research shows.

RATs can help improve access to testing, without ramping up RT-PCR capacity, help identify more positive cases, at a lower cost, and help better handle a possible third wave, shows a project by teams from the Max Institute of Healthcare Management at the Indian School of Business and health nonprofit PATH, funded by the Rockefeller Foundation. The results are from a model-based analysis which uses data from news reports and government portals. The study also includes learnings from pilot projects in Maharashtra and Punjab between April and September 2021.

The research compared several different combinations of RT-PCR and RAT tests and found that it was cheaper, faster and effective if all Covid-19 suspects were first given the RAT test and only those who were symptomatic and still tested negative on the RAT were given the RT-PCR. Using this strategy when testing capacity is overwhelmed across the country or in localised hotspots, and in rural areas where RT-PCR testing capacity is lower, can help India control a surge quickly.

In the second Covid-19 wave, India faced challenges in testing. As of June 2021, towards the end of the second wave, India had conducted 294 tests per 1,000 population, compared to 1,416 tests per 1,000 population in the US and 2,800 tests per 1,000 population in the UK. In India, some people with symptoms of Covid-19 were unable to get tested in the second wave because of a shortage of tests and staff to carry out the tests, we had reported in April 2021. In rural areas, infrastructure to test did not exist, we had reported in August 2021.

In a potential third wave, ramping up test capacity would present similar challenges, addressing which would need development of new labs or installation of additional machines, which is difficult due to resource constraints. Even if that were possible, the turnaround times for tests would continue to stay high. RATs could be used in such a case to quickly detect positive cases, research shows.

How accurate are rapid tests?

Like the RT-PCR test, antigen testing looks for the presence of the SARS-CoV-2 virus in the body. In an antigen test, a swab is taken from a person's nasal cavity and it is tested to detect fragments of proteins which are found on or within the SARS-CoV-2 virus. The RT-PCR tests look for genetic material of the virus, we had reported in August 2020.

To know how good tests are, researchers look at two characteristics: One is the sensitivity of the test or the likelihood that the test will pick up a positive sample. The second is the specificity of the test or the likelihood that a negative sample will be classified as such.

RT-PCR tests have high sensitivity (around 95%) and specificity (almost 100%) with a processing time ranging from three to six hours, and they need additional time and resources for sample transportation and reporting test results.

RATs typically detect the presence of viral particles in the sample within 30 minutes with high specificity (nearly 100%) but low sensitivity (50%–90%), depending on the antigen test kit used. So RATs would miss out on more positive cases than RT-PCR tests.

RAT and RT-PCR combination detects more cases

High-frequency mass testing using low-sensitivity tests (such as RATs) and reducing turnaround time even by a day or two can improve the epidemiological impact of testing, show studies from India, France, the US and Italy.

Going forward, India could rely on a combination of both tests, based on the scenario of disease spread in the country, the research team from ISB and PATH concluded. For instance, if there are very few cases and the spread is slow, and the aim is to identify every positive case, using RT-PCR tests would suffice. But in case of a surge, such as during the second wave, a combination of both testing techniques would help identify more cases. Similarly, a combination would work better for localised hotspots or sudden surges. RATs would also help in testing in rural and remote locations where RT-PCR capacity is low.

"We are not using Rapid Antigen Tests enough," said Gautam Menon, a professor of physics and biology at Ashoka University. "They detect Covid-19 at the point when you are most likely to infect others," he said, adding that RT-PCRs might sometimes be too effective and give positives even when a person is past being infectious.

The researchers from ISB and PATH also conducted diagnostic demonstration studies or pilots in Ahmednagar in Maharashtra, and in Mohali in Punjab. For this, the testing ecosystem was created by the public health department, which provided the space and laboratory technicians for testing. PATH trained these technicians and gave technical assistance, test kits and confirmatory diagnostic technologies. The demonstration studies used existing RT-PCR capacity--roughly 600 tests per day per lab.

They compared four different combinations of RATs and RT-PCRs.

Twelve times the number of people can be tested by the RAT+RT-PCR, as compared to using RT-PCR in 70% of tests, and six times the baseline, the researchers found. It can also prevent excessive burdening of the labs by selectively utilising the limited RT-PCR capacity only for those individuals who are symptomatic and test negative on the RAT and not for all suspects.

The RAT+RT-PCR combination has a sensitivity of 77.8%; that is, it detects 77.8% of positive cases, compared to 81.9% in the baseline. Despite this reduction in sensitivity, this algorithm can find more positive people--close to eleven times--compared to using RT-PCRs 70% of the time, and more than five times compared to the baseline. Test sensitivity improves to 81.9% by using newer generation RAT kits, the research found.

"You can compensate for the lower sensitivity of RATs by testing more," Menon said.

A higher proportion of people in the RAT-RT-PCR combination receive a confirmed diagnosis within one hour--94.4%--instead of 30% in the 70% RT-PCR algorithm and 66% at baseline.

"In a hotspot, RATs help you eliminate those who don't have the virus and quickly detect those who do," said Menon. This is important to control a surge, he explained, in contrast to what had happened in Delhi, for instance, during the second wave, when RT-PCR results would take three to four days.

RT-PCR tests and RATs cost Rs 500 and Rs 150 each, respectively (according to previous studies and field experts who conducted the pilots). The cost per person tested reduces to Rs 178 in the RAT+RT-PCR algorithm, compared to Rs 395 in the 70% RT-PCR algorithm and Rs 268 at baseline.

Some variations of the RAT+RT-PCR algorithm, such as conducting the follow-up RT-PCR test for all RAT-negatives instead of just symptomatic RAT-negatives, and directly testing everyone using RT-PCR, result in worse performance--they found a lower number of positives and reduced access and affordability.

India's testing strategy

As of August 2020, 85% of the tests in India were reportedly by RT-PCR. The Indian government does not provide updated disaggregated data for testing by different methods. A press release from November 2020 had said that 46% of tests were conducted using RT-PCR while 49% used RATs. We have reached out to the Ministry of Health and Family Welfare (MoHFW) and the Indian Council of Medical Research (ICMR) for disaggregated data on testing, and will update the story when they respond.

In March 2021, the central government urged states to conduct at least 70% of overall testing by RT-PCR. Then, in May 2021, the ICMR suggested that RATs be used to support limited testing capacity overburdened by the second wave and be ramped up across health facilities and through testing booths at community centres and offices. The short turn-around time of 15-30 minutes "offers a huge advantage of quick detection of cases and opportunity to isolate and treat them early for curbing transmission", the ICMR said.

The ICMR guidelines from September 2020 asked that RATs be preferred for routine surveillance in hotspots and those who are symptomatic but negative on the RAT, be re-tested with the RT-PCR.

We have reached out to the ICMR and the MoHFW to ask for their view on ramping up RAT testing in times of a surge and will update the story when we receive their response.

There is no standardised testing strategy across states and states can decide their own strategy, and different districts, even in the same state, may have different rules for how these tests are used. For example, in one of the demonstration exercises in the research project, the testing facility was dependent on RAT because they did not have enough RT-PCR tests.

In general, availability of resources and prevailing norms within the state were determining what was followed in practice, the research found. Another factor was the preference of beneficiaries--those being tested might prefer the RT-PCR over a RAT.

Challenges in RAT testing

Though a combination of both kinds of tests would be more effective than one kind alone, implementing such a combination would be challenging. For instance, health facilities would have to ensure that all suspects receive a RAT, and follow up on those who are symptomatic but get a negative result for a RAT test.

More personnel (laboratory technicians and data entry operators) who are well-trained in infection prevention practices would be required at RAT centres to ensure coordination with the RT-PCR labs. For this, a dual swab collection strategy where two samples are collected--first sample for RAT and second for RT-PCR--from the same suspect may help, the researchers observed based on the pilot studies.

Additionally, all health facilities should have a high quantity of RATs to ensure that all suspects are able to get screened through RAT. Moreover, labs would require the newer RAT test kits that have higher sensitivity, which may take longer to procure.

Also, this algorithm might not work for all situations. For example, if the focus of a state is on avoiding missing any positive cases, rather than simply finding more positive cases, implementing an alternative algorithm having an almost perfect sensitivity would be a better choice for that state. The World Health Organization does not recommend RATs when Covid-19 transmission is low.