Saturday, September 02, 2023

UK HSA: Situational Assessment For SARS-COV-2 Variant BA.2.86


Now that 90% of the world's nations are no longer reporting COVID hospitalizations and deaths (see No News Is . . . Now Commonplace), and with the WHO moving to monthly (not weekly) epidemiological reports, we find ourselves facing an uncertain fall - and an emerging BA.2.86 variant - with far less real-time data than we'd like. 

The decision to declare `victory' over the pandemic, and `move on' by treating COVID as if it was equivalent to the `flu', was motivated by widespread (and understandable) pandemic fatigue, economic concerns, and political necessities. 

Of course, for it to work, the SARS-CoV-2 virus would have to cooperate.  While it's true we've seen far fewer hospitalizations and deaths over the past 6 months, Long COVID continues to plague, and sometimes permanently disable, millions of those infected.

AHA: COVID-19 May Trigger New-Onset High Blood Pressure

Study: SARS-CoV-2 Infection and Viral Fusogens Cause Neuronal and Glial Fusion that Compromises Neuronal Activity

JAMA: Additional Evidence Of A Post-COVID/Diabetes Link

Nature: Long-term Cardiovascular Outcomes of COVID-19

And as the SARS-COV-2 virus evolves and mutates, the number of pharmacological treatment options continue to dwindle (see ECDC: SARS-CoV-2 Variant Mutations Conferring Reduced Susceptibility to Antiviral Drugs and Monoclonal Antibodies), and vaccines become less effective. 

While a `milder' Omicron lineage has reigned for the better part of two years, the SARS-CoV-2 virus continues to evolve, as it circulates in both human and non-human hosts (deer, mink, rodents, etc.).

The emergence of a dominant post-Omicron lineage at some point may not be inevitable, but given the mutability of the virus, it is a pretty good bet.   

Whether that is happening right now is up for debate. BA.2.86 represents the biggest antigenic leap we've seen with COVID since Omicron burst onto the scene in the fall of 2021, but our collective switch to a politically expedient `Don't test, don't tell' strategy deprives us of badly needed data. 

Right now, we don't know how well this variant is transmitting, the extent of its spread, or much of anything at all about its severity (or lack, thereof).  BA.2.86 could turn out to be a flash in the pan, unable to compete with more transmissible XBB variants. 

Conversely, BA.2.86 might be a contender. Or possibly a springboard for one of its descendants.  Even it doesn't currently have the `right stuff' to conquer the world, it demonstrates that big leaps in COVID's evolution are still possible. 

Although governments and public health entities are quick to point out there is `no evidence' that BA.2.86 poses an immediate threat, they are also generating technical documents (see here, here. here & here) at a furious pace, and the UK is altering fall vaccination campaigns (see UKHSA To Move COVID/Flu Jabs Forward Due To Concerns Over BA.2.86) with a sense of urgency we haven't seen in nearly 2 years.  

Yesterday, for the second time in less than two weeks, the UK's HSA released a technical assessment on what is known (and not known) about the emerging BA.2.86 variant (see below).  As you'll see, there are far more questions than answers. 

I'll have a brief postscript after the break. 

 Research and analysis

Situational assessment for SARS-CoV-2 variant V-23AUG-01 (BA.2.86)

Updated 1 September 2023

Applies to England

Part 1. Context and UK cases

As of 10am, 31 August 2023, 25 BA.2.86 genome sequences are available on the international genomic data-sharing platform, GISAID. These originate in 8 different countries:

  • 10 in Denmark
  • 4 in Sweden
  • 4 in USA
  • 2 in Portugal
  • 2 in South Africa
  • 1 in Canada
  • 1 in Israel
  • 1 in UK

Two further UK cases, one in England and one in Scotland, have been identified and genome sequence data will be available on GISAID shortly. This is a dynamic situation changing daily.

Sample dates, where known, range from 24 July 2023 (Denmark, South Africa) to 22 August 2023 (USA) (Figure 1).

The first UK case was reported in the previous risk assessment, published 18 August 2023. All UK cases were identified through hospital testing and have no known recent travel history through routinely collected data.

The first UK case was mildly unwell and the second UK case (England) did not have respiratory symptoms. The third UK case (Scotland) was symptomatic. The samples for the 2 new cases were sequenced through routine surveillance of hospital test-positive cases.

A number of additional countries have also made formal or informal announcements of BA.2.86 detection in wastewater. There is no internationally consistent repository for wastewater genomic data.

Figure 1 is a bar showing sequences grouped by week of sample collection (GISAID upload date is used where sample collection date is not available in one case). Total number of sequences per country are shown in the figure legend.

One sequence from both Denmark and USA, and 2 sequences from South Africa have collection dates available on GISAID from the week beginning 23 July 2023.

There was one sequence each from Denmark, Israel, and USA with a collection date from the week beginning 20 July 2023. One sequence from USA and Sweden, and 3 sequences from Denmark have a collection date in the week beginning 6 August 2023.

Three sequences from the UK, 3 from Sweden, 2 from Portugal and 4 from Denmark have a collection date from week beginning 14 August 2023.

One sequence from USA and one sequence from Denmark have a collection date from week beginning 20 August 2023. There was one sequence from Canada with a submission date from the week beginning 27 August 2023. 

Figure 1. Epicurve of BA.2.86 genome sequences on GISAID, including additional 2 new UK cases  

Part 2. Variant Technical Group assessment

Meeting and assessment 29 August 2023. The UK Health Security Agency (UKHSA) is aware of new data since this date and continues to assess all available information.

Through the limited available global genomic surveillance, the variant is present in multiple countries on multiple continents, detected at a low prevalence amongst clinical cases or in wastewater. Although an increasing number of countries are reporting detection, there is as yet no clear signal of growth within any of these individual countries.

The BA.2.86 phylogeny shows one sublineage within which most European cases are located but does not otherwise have a high degree of substructure. The time of most recent common ancestor (tMRCA) is estimated at 3 June (range 29 April, 1 July) assuming exponential growth.

BA.2.86 is an outlier in terms of geographic dispersion when compared to other nodes in the SARS-CoV-2 global phylogeny in 2023 with similar tMRCA and which are still circulating. However, it is not the most extreme outlier. This analysis does not incorporate countries detecting BA.2.86 through wastewater.

The group considered hypotheses of a mass gathering event seeding multiple countries, an ongoing outbreak in a country without surveillance, or widespread community transmission undetected by surveillance. All 3 possibilities were still considered plausible, though widespread high-level community transmission is not best supported by the phylogeny.

No conclusions can be drawn about the fitness of the variant based on this data, and a full range of options – from less fit than other circulating variants, to a large jump in fitness – are still possible, given the available data.

There is no laboratory data available. Two samples are in culture in the UK and we are also in contact with international partners. Neutralisation and other phenotypic data is still likely to be one to 2 weeks away at minimum in the UK.

The extant UKHSA variant of concern definition requires us to demonstrate (or confidently predict) a detrimental change in biological properties, as well as a growth rate compatible with displacement or maintenance. At present there are a wide range of possibilities for the fitness and growth of the variant and there remains uncertainty about the impact of the mutations present.

BA.2.86 does not, therefore, meet this definition of a variant of concern. The Variant Technical Group discussed whether the current surveillance context required an updated approach to designating and acting on variants. However, any such updated definition of a variant of concern would include a higher level of confidence on positive growth than is available at present for BA.2.86.

Sources and acknowledgements

  • Variant Technical Group
  • Analysis submitted by:
  • UKHSA Genomics Public Health Analysis Team
  • UKHSA COVID vaccines and epidemiology team
  • Public Health Scotland
  • Andrew Rambaut
  • Erik Volz

          (Continue . . . .)

Without better data, it is impossible to say how much of a threat BA.2.86 poses, now or in the immediate future.  We will simply have to wait and see. 

But even without a new lineage, COVID is back on the ascendant here in the United States, and in many other countries around the globe.  It still kills thousands of people every month, and even mild infection is well worth avoiding if you can. 

The U.S. and UK, and other countries will be rolling out a new vaccine this fall, and while it remains to be seen how effective it may be against BA.2.86 infection, it is still expected to reduce hospitalizations and deaths.  

Since I consider even a little protection preferable to none, I plan to roll up my sleeve (for both COVID and Flu vaccines) this fall.  I'll also be adding some extra layers of protection; wearing a KN-95 face mask, using hand sanitizers, and avoiding crowds whenever possible.

Some people may consider that excessive, or premature.  But as a Floridian, I've learned that when a CAT 1 hurricane is predicted to make landfall, it is prudent to prepare for a CAT 2 or CAT 3 storm.  

If the worst doesn't happen, I don't feel foolish.

I feel lucky.