‘Stealth’ Omicron, a decline in cases, and preventing the next variant
CLINICAL MATTERS
Whenever new scientific information is released on COVID-19, misinformation isn’t far behind. There are many factors that contribute to this. Scientists being unable to properly communicate their findings is one. Media playing up preliminary data to sell clicks and papers is another. Sometimes it is just an honest mistake. The consequences of fake news, however, are all the same—panic, fear, and a whole lot of noise.
Since the start of the pandemic, academics who are active on social media have collectively cringed at the degree of misinformation and disinformation in both mainstream and nontraditional platforms. There is only so much fact checking that can be done and, in some cases, the experts themselves get fact checked by non-experts, who either have an agenda or are just confused by all the specialized terminology. Despite these hardships, it is important to continue to engage since misinformation and disinformation do outsized harm if not checked and countered.
One recent bit of deceptive news was the report that a sublineage of Omicron, termed “stealth” Omicron or BA.2, could not be detected on RT-PCR testing. This sent people into a panic because of the mistaken impression that one might test negative on RT-PCR even if they had this strain of Omicron. A quick check with reputable sources shows that BA.2 can definitely be detected by all current RT-PCR tests.
Omicron is not just one viral lineage but refers to the original B.1.1.529 and its three sublineages BA.1 (also known as B.1.1.529.1), BA.2 (also known as B.1.1.529.2), and BA.3 (also known as B.1.1.529.3). The World Health Organization (WHO) treats all these four lineages as Omicron, and there is no evidence that one lineage is more virulent or more likely to avoid vaccines than the other. The BA.1 sublineage is the most common Omicron sublineage globally. It was the first sublineage identified among returning overseas Filipinos. The original Omicron B.1.1.529, BA.1, and BA.3 have mutations in the spike protein known as the 69-70 deletions. BA.2 does not have these two mutations. This is significant since some RT-PCR kits cannot detect the spike protein gene, or S gene, when these two mutations are present. This phenomenon is known as S gene dropout.
RT-PCR remains the gold standard for detection of SARS-CoV-2. It turns positive when the genetic material of the virus is present in a sample from a patient. RT-PCR works by using specific short sequences of DNA known as primers to amplify and detect viral genes. RT-PCR kits usually use two or three target genes for amplification to detect SARS-CoV-2. Among these genes are S (spike protein), N (nucleocapsid protein), E (envelope protein), ORF1ab (open reading frame), and RdRp (RNA-dependent polymerase). Not many kits used locally target the S gene, but the ones that do use it in conjunction with other genes. Therefore, while Omicron with the 69-70 deletions exhibit S gene dropout, the other genes will amplify normally and still be detected on RT-PCR.
When Omicron was first described, one of the alternative ways to detect it was to check for S gene dropout. This was especially useful in places with limited genome sequencing capabilities. Sequencing remains the best way to identify variants of concern but is expensive and highly technical. S gene dropout, however, is not unique to the Omicron variant. The Alpha variant also has the 69-70 S protein deletions and will show S gene dropout. Fortunately, the dominant variant in most countries when Omicron initially showed up was Delta, which does not exhibit S gene dropout. Therefore, demonstrating S dropout when many cases in the community are Delta was a presumptive test for Omicron.
Since BA.2 is unique among the Omicron sublineages in not having the 69-70 deletion, it does not exhibit S gene dropout. This is why the term "stealth" was used because it was an Omicron variant that escaped presumptive detection when one uses an RT-PCR kit to look for S dropout. The term “stealth” has nothing to do with escaping detection by RT-PCR. It is instead an indication that it does not have S gene dropout and will test positive for this gene, along with whatever other genes are targeted by the RT-PCR kit.
Filipino scientists doing genomic sequencing were aware that BA.2 was already circulating in certain countries. This is why we did not adopt the WHO recommendation to use S gene dropout as a screening test for Omicron. In addition, not very many RT-PCR machines in the Philippines were compatible with the test kits that used the S gene for detection. The decision was to go ahead and do full genomic sequencing for suspected Omicron samples since we have this capability. The first Omicron sublineages detected in the Philippines were BA.1. This sublineage was repeatedly detected in returning Filipinos from abroad. Very few BA.1 from these travelers got through to the community. This is strong evidence that our quarantine protocols work.
BA.2 somehow made its way into the community. Whether it was simply undetected in a traveler who completed quarantine or there was a break in quarantine rules is unclear. It spread rapidly in the community, and samples from local cases are now almost all BA.2. There is no evidence that BA.2 is any worse or better than BA.1 in terms of clinical presentation or breakthrough infection. Cases are mostly mild, especially among fully vaccinated individuals. There is no reason to suspect that BA.2 or “stealth” Omicron is behaving any differently compared to other Omicron sublineages.
The Omicron wave is receding from Metro Manila and is moving out into the provinces. The steep drop in cases and the declining healthcare utilization in NCR shows that vaccination has protected our people and has removed the fangs from COVID-19. Provinces with low vaccination rates may not fare as well, which means more effort should be exerted in reaching the remaining unvaccinated holdouts. The vaccination of the five to 11 age group will further increase community immunity to COVID-19 and will mitigate the impact of future spikes in infection. Even with breakthrough infection, cases among the vaccinated people tend to be mild, less infectious, and are less likely to mutate. Vaccination not only saves lives, it can also prevent the rise of dangerous new variants.