The Next COVID-19 Wave?

WHO Estimates The XE Subvariant More Transmissible Than Even BA.2

As the Omicron BA.2 subvariant recedes from the public consciousness (and most of the Pandemic Panic with it) the WHO is watching a variant of the subvariant, dubbed “XE", which the WHO estimates is 10% more contagious than BA.2.

According to an epidemiological update published March 29 by the World Health Organization, estimates show XE is 10% more transmissible than BA.2, however the findings require further confirmation.

Will the Pandemic Panic Narrative receive a new lease on life? Certainly the corporate media is likely to continue pushing the narrative, if only to avoid admitting the obvious: BA.2 has been a pandemic nothingburger.

Will XE be any different? It is too soon to predict what XE will do with any degree of certainty, but its lineage as an Omicron subvariant does offer some tantalizing clues.

Recombinant Virus: BA.1, Meet BA.2

The first thing to note about XE is that it is a recombinant variant. Recombinant viral strains are quite common among infectious respiratory pathogens, particularly when multiple variants are circulating in a geographic locale at the same time. As the different strains intermingle within an infected host, they can blend together to form a new strain.

The WHO monitors recombinant variant strains, and has been actively tracking three Omicron subvariants, XD, XF, and XE for the past few weeks, as was noted in the WHO epidemiological update of March 22:

Recombination of variants of the same virus is a natural phenomenon and can be regarded as an expected mutational event. WHO has been notified of several recombinant variants, either recombination between Delta and BA.1 variants, or BA.1 and BA.2 variants. The same monitoring and assessment process is applied to these recombinants as for any other emerging variant, after verification and exclusion of potential contamination or co-infection. Two Delta and Omicron recombinants and one BA.1 x BA.2 recombinant have now been given Pango lineage designations XD, XE and XF. None of the preliminary available evidence indicates that these recombinant variants are associated with higher transmissibility or more severe outcomes. WHO continues to monitor recombinant variants, alongside other SARS-CoV-2 variants, and will provide updates as further evidence becomes available.

XE is the subvariant which evolved from the blending of the Omicron BA.1 and BA.2 strains. As the March 22 update shows, its initial detection raised no red flags. It was merely another subvariant to be monitored. Even more noteworthy is the fact that XE did immediately present with a greater transmissibility.

Increasing Cases

While BA.2 was grabbing headlines despite a lack of severe cases, the XE recombinant variant also became slightly more prevalent, particularly in the UK, where it was first sequenced in mid January, and has since been identified in over 600 cases.

A total 637 cases of XE – a recombinant of Omicron BA.1 and BA.2 – have been confirmed in the UK so far. The earliest of these has a specimen date of 19 January 2022. There is currently insufficient evidence to draw conclusions about growth advantage or other properties of this variant. We continue to monitor all recombinants closely, routinely through our world-leading genomic surveillance and sequencing capability.

However, beyond its existence, very little is known about XE's unique characteristics. Other than a variable growth rate, the strain is still too new for much factual information about the strain to be established, although by the release of the March 29 epidemiological update, the WHO was estimating XE to be 10% more transmissible than BA.2.

The same process of risk assessment is applied to recombinant variants as for any other emerging variant. Since the epidemiological update published on 22 March 2022, no new evidence indicates that the recombinant variant assigned XD Pango lineage (Delta-Omicron) is associated with higher transmissibility or more severe outcomes. The XE recombinant (BA.1-BA.2), was first detected in the United Kingdom on 19 January and >600 sequences have been reported and confirmed since. Early-day estimates indicate a community growth rate advantage of ~10% as compared to BA.2, however this finding requires further confirmation. XE belongs to the Omicron variant until significant differences in transmission and disease characteristics, including severity, may be reported. WHO continues to closely monitor and assess the public health risk associated with recombinant variants, alongside other SARS-CoV-2 variants, and will provide updates as further evidence becomes available.

Given that BA.2 is dominant pretty much the world over, and has been identified as the dominant strain in the US, a 10% growth advantage over BA.2 is fairly significant, at least as regards community spread of the virus. However, as the data on BA.2 reminds us, greater transmissibility is not the same as greater virulence.

BA.2: The Phantom Menace?

BA.2 may be the dominant variant, but it is “stealthy” primarily because it is fairly mild. If XE is more transmissible than BA.2, it is by no means certain that it will produce more severe illness. Based on what has been observed with the various Omicron strains, the current anticipation should be that XE will be similarly mild.

SARS-CoV-2 Is Fairly Infectious All Around

We should also understand that all strains of the SARS-CoV-2 virus are relatively contagious, compared to other infectious respiratory pathogens. A recent “human challenge” study of how infectious SARS-CoV-2 actually is successfully infected 18 of 34 test subjects using an inoculating dose (10 TCID50) that was approximately 1/1000 of the dose (10⁴ TCID50) typically used in similar challenge studies for other infectious respiratory pathogens.

Irrespective of any other conclusions which may be drawn from the study, that the study authors were able to use such a small inoculum dose to infect more than half the study group illustrates that the SARS-CoV-2 virus, even in its original incarnation, is an highly infectious pathogen.

As Omicron has proved to be far more infectious than the original virus, and BA.2 more infectious still, a strain that is estimated to be 10% more infectious than BA.2 must be considered to be extremely infectious and transmissible.

A New COVID-19 Wave Unlikely?

As transmissible as XE is estimated to be, the human challenge study also noted an important reason why a low inoculum dose could be used: SARS-CoV-2 is a novel pathogen that human immune systems are just now learning to fend off (emphasis mine) .

In human challenge studies with other respiratory viruses, such as influenza viruses and respiratory syncytial virus, inoculum doses are typically also much higher at 10⁴–10⁶ TCID50 because all volunteers have been exposed multiple times throughout life to those viruses, with pre-existing immunity reducing susceptibility and resulting in substantially lower peak viral loads at 10³–10⁴ copies per milliliter by PCR.

Other infectious respiratory pathogens are known quantities, so to speak, and so a greater inoculum dose is needed to produce infection.

While the SARS-CoV-2 virus is novel, it has been circulating in the wild for over two years now, and human immune systems, being necessarily a quick study on defending against new pathogens, have been learning how to fend off the virus. The study's authors concede this point when they state the study might not be reproducible due to a lack of a suitable study population.

However, although globally there are groups that remain naive to SARS-CoV-2 vaccination and infection, it is unlikely that a larger study in seronegative volunteers will be achievable going forward, and this study may, therefore, remain the only one of its kind.

Amplifying this point further, while some studies have indicated there was little cross-immunity from other coronaviruses against SARS-CoV-2, other studies have demonstrated significant cross-immunity among SARS-CoV-2 strains, particularly the Delta and Omicron strains. As a direct consequence, while a particular strain may show properties which make it more transmissible, the proliferation of strains has had the effect of making the human host a harder target, thereby mitigating much of that transmissibility.

Broadly speaking, this is why infectious respiratory pathogens tend to attenuate over time to produce milder disease and fewer severe infections. It is not merely that viruses evolve to become less dangerous, but also that human immune systems adapt and become better at warding off infectious respiratory disease.

This may explain why BA.2 has been reduced to a “stealthy" virus—Omicron has already primed human immune systems against it. By this same logic, the XE recombinant variant may prove to be just as “stealthy” and for the same reason: the novel pathogen is no longer quite so novel.

Let us be clear on this point: a “stealthy” virus is by definition not producing significant incidence of actual disease. It may circulate, but it is finding relatively few susceptible hosts. “Stealthy” infectious respiratory pathogens are never a cause for alarm.

This will prove bad news for the promoters of the Pandemic Panic Narrative, as it reduces the likelihood that XE or any other variant will have the pandemic potential of the original SARS-CoV-2 virus, or Delta or even Omicron. With each strain to which we are exposed, our immune systems become better equipped to fight off all strains, including at least some future strains. Only strains with significant evolutionary variation from prior strains (e.g., Omicron) will have significant pandemic potential.

Thus, despite early estimates of greater transmissibility, the potential for XE to produce significant numbers of infections, let alone symptomatic cases, is diminished by the earlier successes of original SARS-CoV-2, Delta, and Omicron. While only time will reveal XE's true pandemic potential, the odds of it having significant pandemic potential are relatively low at this point.

The data shows this to be the case. With only 637 identified cases in the UK since January, any “wave" of XE infection is on course to be little more than a ripple.