UK advisers warn of Original Antigenic Sin and a potential new variant with 35% case fatality

More fear porn from the notoriously wrong modellers or something to keep an eye on?

SAGE stands for the Scientific Advisory Group for Emergencies. They provide scientific and technical advice to support government decision making during emergencies. I’m guessing they chose their name to sound mysterious and wise but more often than not they make speculating predictions that never come to pass.

However, these are the best experts in the country, the crème de la crème, so I like to keep an eye on what they are thinking. Even if not for their predictions but for the likely path government will follow when listening to them.

Their latest meeting minutes and papers, held in February 2022, were updated and published recently. One of the papers, by the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) caught my eye, as they looked at the long term evolution of SARS-CoV-2.

Their paper is interesting because it hints on the quantum nature of viruses, as explained here, which should leave anyone with cause for concern.

They predict that antigenic drift will almost certainly lead to current vaccine failure. Furthermore, they caution that the milder symptoms associated with Omicron is likely a chance event. The next variant to achieve UK or global dominance is likely to have the same pathogenicity as previous variants. They claim that the loss of virulence as viruses evolve is a common misconception.

It certainly would be a misconception if the virus is a de-attenuating live vaccine as discussed here.

New variants and Original Antigenic Sin (OAS)

Almost as if NERVTAG know the likely origins of SARS-CoV-2 and Omicron, they say that new variants do not necessarily emerge from previously globally dominant variants, e.g. Omicron did not arise from Delta and new variants don’t necessarily arise from where vaccine selective pressure is greatest. The phylogenetic tree of SARS-CoV-2 is certainly very strange and unpredictable.

They also rightly worry about focussing on the spike protein too much. With a population highly vaccinated against the Wuhan spike and the Wuhan spike alone, any changes to the spike OR any other sites in the genome could have major impacts on transmission, fitness and diseases outcomes.

Due to this complete focus on the spike, the vaccine has elicited a much narrower immune response when compared with natural infection. As discussed previously, one of the major concerns about these vaccines was OAS and whether the immune response would forever target the Wuhan spike protein, long after it had mutated. NERVTAG clearly also have had similar concerns. They suggest this scenario is almost certain and will have a medium impact. They define antigenic sin as vaccination resulting in an immune response that is dominated by antibodies to previously experienced viruses or vaccines. The paper says that this means it becomes difficult to revaccinate to induce antibodies to new strains. However, they say it has not been reported yet so they consider the possibility of it occurring less likely.

Future scenarios

NERVTAG identified four plausible future scenarios. They thought the most unlikely scenario was one similar to Omicron, a variant with decreased virulence.

Their first scenario is the one that was of most concern. This was a scenario where a variant caused severe disease in a greater proportion of the population than has occurred to date with protentional vaccine escape. For example, with similar morbidity to SARS-CoV (10% case fatality) or MERS-CoV (35% case fatality).

They suggest that this could be caused by point mutations or recombination with other hosts or viral genes. Another way for such a variant to arise is by recombination between two variants, one with a major change to the spike protein and the other with more efficient replication and transmission determined by internal genes.

NERVTAG think that the likelihood of genotypic changes in internal genes is likely whilst circulation of Covid is high. They also predict that the likelihood of increased severity phenotypes is realistically possible.

The predicted impact of the new variant is understandably high. They say that the spike based vaccines would continue to provide protection against serious disease but that an increase in morbidity and mortality would be expected because the vaccines don’t provide sterilising immunity.

Non-pharmaceutical Interventions (NPIs)

Another interesting observation from the report is one that many of us have been saying for the last few years. They say that NPIs such as mask-wearing and social distancing shape the environment in which a virus transmits and may act as selection pressure for increased viral transmission.

They use the example of social distancing, saying that this may make a virus able to better transmit through the air have a fitness advantage and therefore be better able to survive and replicate.

So not only have NPIs achieved little in changing the direction of the pandemic, they have probably made it worse.

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Hopefully this is more fear porn, produced to try to keep some restrictions just as we are removing most of them. However, with the origins of Covid unknown and the lab leak theory the most plausible, their considerations should be taken into account. Especially, if the virus is a de-attenuating live virus, trying to find its way back to peak fitness.