Is the current testing, sequencing strategy missing Omicron cases in India?

Positive samples sent for genome sequencing to confirm for the Omicron variant are almost primarily restricted to international passengers. Not only are the testing rates across India low, most of the RT-PCR test kits used in most States do not have the S-gene target in the primer, which can detect the BA.1 sub-lineage. Also, the Omicron variant causes only mild disease in people who are fully vaccinated or previously infected. But there would have been a surge in cases if the variant is already present here as Omicron spreads faster.

Over 100 Omicron variant cases have been detected so far in 11 States in India. Except for one case of a medical doctor in Bengaluru who has been confirmed to be infected with the Omicron variant, the remaining have been detected in international passengers arriving in India and their contacts.

A November 30, 2021 circular from the health ministry clearly mentions that effective December 1, all passengers arriving from specified “at-risk” countries will be required to undergo an RTR-PCR test on arrival. And random testing is to be done on 2% of the total flight passengers arriving from other countries. Incidentally, the at-risk countries list has not been updated since the circular was sent on November 30; it includes only Europe, U.K and 11 other countries.

While all positive samples are to be sent for genome sequencing, passengers arriving from at-risk countries will have to undergo home quarantine for seven days, retest on the eighth day of arrival in India and if negative, further self-monitor their health for the next seven days.

The testing strategy adopted now looks quite similar to the one put in place early last year when testing was confined to international passengers and their contacts if the index case tests positive. While over 90 countries have confirmed Omicron variant, the testing in India is confined to international passengers. Positive samples sent for genome sequencing to confirm for the Omicron variant are almost primarily restricted to international passengers. Is India missing to identify the Omicron variant in the community by not at least randomly sequencing a few positive samples? Absence of evidence is surely not evidence of absence.

“This depends on the extent to which we believe the Omicron variant has already spread in the country. Levels of overall testing are currently fairly low, at the level of one-three million daily. But the problem is that most of these tests are being done in a small number of States, mainly Kerala, Maharashtra and Karnataka. Because of this, it is hard to figure out to what extent silent spread has already begun in other parts of the country or whether cases are picking up,” says Dr. Gautam Menon, Professor of Physics and Biology at Ashoka University.

Based on the speed at which the Omicron variant spreads, scientists have said one infected person can spread it to three or more people. Scientifically speaking, the R0 of the Omicron variant is over 3. The Omicron variant has been found to spread two-three times faster than the highly transmissible Delta variant. As a result, in other countries, Omicron cases are doubling every two to four days, which is far shorter time frame compared with the Delta variant.

Since the variant spreads faster than the Delta variant, there would have been a surge in cases in India if it is already present in the community. “For now, we have nothing that suggests a large-scale rise in cases, which might have been a consequence of Omicron,” Dr. Menon says in an email to me.

Not only are the testing rates across India low, most of the RT-PCT test kits used in many States do not have a S-gene primer. The S-gene dropout in the BA.1 sub-lineage is used as a proxy for identifying the Omicron variant. In the absence of test kits with a S-gene primer, only genome sequencing can even identify the variant.

“We need more random testing to detect community spread in those States which are not already testing well, and we need to sequence some fraction of the positive cases, both symptomatic and random, on a priority basis to look for Omicron. Right now, we don’t have any evidence of large-scale transmission of Omicron but that could simply be an artefact of lack of testing,” he says.

In the absence of increased testing and genome sequencing, another layer of complexity in noticing a surge in cases might be related to the mild nature of the disease caused by the variant in those who are already protected. While the Omicron variant can cause reinfections in people who have been previously infected and also cause breakthrough infections in fully vaccinated people and even among those who have received a booster shot, the cases mostly have only mild disease.

With a large percentage of the population in India being naturally infected, over 57% fully vaccinated and over 87% having received the first dose, most of the cases caused by Omicron may be mild, thus not being tested. A significant number of people who have been vaccinated might have been previously infected during the deadly second wave. This combination of infection plus vaccination produces hybrid immunity, which is more protective than just the vaccination or infection alone. This could be another reason why India cases in the community might have been missed.

One of the first Omicron positive cases detected in India on November 22 was a medical doctor in Bengaluru who had no travel history or contact with any international passenger. This suggests that the possibility of the variant already being present in the community cannot be completely ruled out. “That [case] is certainly evidence for some degree of community transmission, since there is no apparent connection to a case of international travel. However, not all such infections will necessarily lead to an explosion in cases and it is possible that this was a one-off event,” Dr. Menon says.

“I personally think it is just a matter of time till we see Omicron cases rising, perhaps by January. There is some level of protection, one assumes, from the fact that many Indians have sustained a recent Delta infection and many are now vaccinated as well. This may lead to overall milder cases, which might be one reason why we have not seen any sizable jump in hospital admissions,” he adds.

Kerala health secretary Dr. Rajan Khobragade says that besides sequencing positive cases of international passengers, Kerala will sequence positive cases from huge clusters and superspreader events to rule out the Omicron variant in the State. But Dr. Menon feels it might be necessary to sequence some fraction of symptomatic COVID-19 patients across the country to assess the presence of COVID-19 and this specific variant in the population, and also test randomly, looking for the presence of Omicron in a fraction of those that test positive. “Only then can we assess the extent of community spread,” he says.

Published in The Hindu on December 18, 2021