Dr Andrew Page is Head of Informatics at the Quadram Institute and leads the genomic surveillance work which has been undertaken by the Quadram Institute and other UK centres since March 2020 for the UK’s National Health Service (NHS) and public health agencies.

After almost two years of the COVID-19 pandemic, the rollback of the Plan B restrictions in England last week is seen by many as a sign of how we’re starting to live with the virus. For us in the frontline of COVID-19 surveillance, living with the virus means keeping an ever-vigilant watch for what the virus might do next.

We’ve been doing this since the start of the pandemic, as part of the UK-wide COVID-19 Genomics UK Consortium (COG-UK), which pioneered COVID-19 genome surveillance across the world.

Because viruses mutate naturally over time, we realised that we could track these changes by reading the genetic sequences of the virus. It’s vital information, for tracking localised outbreaks as well as the spread across continents, and the globe. And, as shown first by the “Alpha” variant, it flags up when these mutations lead to new “Variants of Concern” where the mutation gives the virus a boost in its abilities to transmit or cause disease.

In November last year Delta was the prevalent variant, and if you’d asked me what things would look like at Christmas I would have guessed that Delta would still be around, with the AY.4 Delta lineage being gradually replaced by the emerging AY.4.2 lineage.

However as we’ve seen in this pandemic things can change in the space of a few days. At the end of November South African scientists identified half a dozen samples with a whole new set of mutations and we’re seeing rapidly increasing case counts in the Gauteng province.

Even though there were only a handful of genomes, we knew this was going to be a game changer.

These samples were quickly designated as Omicron and swept the world faster than all other lineage that had gone before. Travel restrictions were quickly imposed, but unbeknownst to everyone this was already a lost cause; looking back at sequenced genomes we now know that thousands of cases of Omicron were already circulating in the UK in late November 2021.

The UK has one of the strongest public health surveillance systems in the world and has consistently lead from the front with genome sequencing. This meant we could track in near real-time the rapid rise of Omicron in the UK in December and carry out early scientific investigations to assess the severity of illness omicron causes, how effective vaccines are against it, and how easily it transmits.

For omicron, what became clear was that although it is much more transmissible, it causes much less severe illness.

At the Quadram Institute we sequence thousands of SARS-CoV-2 samples every week and as of today, 99% of all samples we are seeing are Omicron with Delta completely displaced. In a way this is good news because a variant that causes mild disease has replaced one that causes more severe disease. It also demonstrates that infection with Omicron imparts immunity to infection from Delta, although how long that immunity lasts is an open question.

What is now clear about Omicron is that it is a “family” of closely related lineages, derived from one common ancestor. These sub-lineages have been called BA.1, BA.2 and BA.3. Whilst they share a common recent history, the COVID-19 Omicron BA.2 lineage contains about 20 more mutations than BA.1. One of these mutations does mean that BA.1 can be distinguished from BA.2 is in a diagnostic test commonly used in the UK lighthouse labs.

The proportion of variants (VOC/VOI) week by week from 1st November 2021 to 30th January 2022. The chart shows the dominance of Delta in late 2020, quickly replaced by omicron (BA.1) and initial rise of omicron (BA.2). Data from : covid19.sanger.ac.uk

Scientists don’t yet fully know how these mutations alter BA.2 .There’s no evidence yet that BA.2 may cause more or less severe illness, but that is under investigation by UKHSA. Work by UKHSA indicates that people who are boosted are still protected to a similar degree regardless of the Omicron lineage they are infected with.

Looking around the world we have seen BA.2 become the dominant lineage, accompanied by mild disease. BA.2’s ability to outcompete BA.1 is evidence that it is more transmissible, and tests are now being run to see if this is the case and why.

Currently, the UK is dominated by the BA.1 lineage, accounting for most of the genomes sequenced and overall cases have come down substantially from the peak in early January. However we can now see in the sequencing data that the BA.2 lineage is growing rapidly, which is a cause for concern.

In sequencing data BA.2 accounts for just 1% of genomes, but this is usually looking back a week or two in the past. More up to date, earlier test data from diagnostic testing (based on S-gene target failures) indicates it now accounts for at least 5% of cases and is doubling in proportion every 4 to 5 days.

At this rate of doubling, we will see the COVID-19 Omicron BA.2 lineage becoming the dominant lineage in February, and this is may bring about another peak in cases.

There are still a lot of people out there who can be infected. The REACT study, which Quadram undertakes the sequencing and bioinformatics analysis for, found that two thirds of people who were infected with Omicron had previously had COVID-19. On a more positive note, it also shows that people who have received a boosted vaccine receive the best protection.

So the next month could see some more bumps in the road out of the pandemic, but there are steps we can all take to protect ourselves and each other. Despite the lifting of some restrictions, government advice remains to get vaccinated or boosted, wear a face covering in crowded indoor spaces, keep rooms ventilated and get tested regularly. That is how you can help counter the threat from this stealth omicron, whilst we keep a close eye on it and any future threats.

“Family tree” of selected SARSCOV2 samples from the start of the pandemic. The animation shows when variants appeared over time. Alpha appears first (cyan, far left) before we see Delta variants taking over (far right). Then, from November 2021 Omicron sweeps in (purple=BA.1) to dominate. At the end, the latest data show Omicron BA.2 (yellow) popping up. Explore the data yourself at https://microreact.org/project/sc2-jan2022