XE and XD variants: what we know today

Geneva, Monday April 11, 2022 – Two new recombinant variants are closely monitored by the World Health Organization (WHO): XE and XD.

Variant XE: more contagious

The XE variant, which is already spreading in the UK, and of which a few cases have been identified elsewhere in the world, is a recombinant variant of the two now well-known Omicron strains: BA.1 and BA.2. XE has three mutations that are not present in the BA.1 or BA.2 strains, depending on theUK Health Safety Agency (UKHSA). While researchers are still studying the contagiousness of XE, recent data indicate that the variant may be 10% more transmissible than Omicron. As such, it should be noted that a report of April 5 from the WHO endorses this assessment, specifying that it must be confirmed.

The first known case of XE was detected in the UK on January 19, 2022. So far, more than 600 cases of XE have been identified there, according to a March 25 report from the UKHSA, representing less than 1% of total sequenced cases.

XE has also been observed in India and Thailand. A case was reported on April 6 in Mumbai and on April 4 the Medical Genomics Center from Bangkok sequenced one.

So far there is not enough evidence to draw conclusions about the transmissibility, severity or effectiveness of the vaccine said Susan Hopkins, UKHSA’s chief medical adviser, in a statement.

However, it is possible to deduce some of its characteristics from the two strains that compose it. ” We know that vaccines are effective in protecting against symptomatic disease for BA.1 and BA.2, and therefore we have every reason to believe that vaccination strategies will have activity in protecting against symptomatic disease caused by XE “, says Professor Andrew Badley (Mayo Clinic, Rochester) to Time magazine.

Another important indication is that ” both BA.1 and BA.2 may escape some monoclonal antibody therapies so these drugs are not likely to be as effective against XE, adds Professor Badley. ” We also know that the other therapies used in particular in the outpatient setting (paxlovid and molnupiravir) should, based on their mode of action, have activity against strain XE he continues.

The UKHSA is currently monitoring the XE strain and two other lines, XF and XD, both of which are recombinations of Delta and Omicron BA.1. So far, the UKHSA says less than 40 cases of XF have been detected, all in the UK (although none have been detected since mid-February). XD has not been detected in the UK, but a few hundred cases, mainly in France, have been reported to global databases.

Variant XD: more virulent than Omicron?

This XD variant, previously called Deltacron, might have a more worrying profile. The genome of this new XD variant was identified in the north of France during routine genomic surveillance during a “ Glow
“.

As of March 18, this XD sub-lineage has been detected in several French regions, but also in Denmark, the Netherlands, Belgium and Germany. In the majority of cases, this recombinant virus was identified in individuals who had not traveled. One of them had however gone to Italy, which is in favor of circulation of the XD variant in this country.

According to Public Health France, as of March 28, 63 sequences characteristic of the XD variant had been detected in our country. These sequences correspond to cases from several regions of metropolitan France, the XD variant representing less than 0.1% of the interpretable genomic sequences.

On Monday April 4, the Institut Pasteur in Paris published its first conclusions on this recombinant, available on the Research Square platform from 32 cases confirmed between January 3 and March 9, 2022.

The researchers indicate that the median age of patients infected with the XD variant is 35 years, similar to what is generally observed with Omicron. However, there are more cases of infection with XD in people under 20 (25.7%) compared to Omicron (11.3%). No cases of XD infection have been observed in people over 70 years of age.

While the majority of cases (54%) had received a complete vaccination (two doses), including 24% with a first booster dose, only three cases (6%) had presented a previous infection with SARS-CoV-2 , which is rarer than with Omicron (14% of the 468 cases analyzed between November 2021 and January 2022).

In France, all cases of infection with the XD variant were symptomatic. The most common clinical signs are headache (61%), asthenia (58%), cough (44%), fever (39%), myalgia (33%). Compared with Omicron, the proportion of cases reporting ageusia or anosmia was higher among subjects infected with the XD variant. Two patients were hospitalized, but none had to be admitted to intensive care.

Thanks to experiments on a mouse model, the team from the Institut Pasteur was also able to determine that the levels of viral RNA in the lungs of mice infected with XD and the BA.1 subvariant of Omicron were comparable, namely 3.7 times lower than those observed in rodents infected with delta. In addition, the viral load in the nasal turbinates of mice infected with XD was 8.5 times lower than that observed in mice contaminated with the BA.1 subvariant of Omicron.

The scientists also concluded that while the mice infected with Delta showed weight loss, those infected with the XD virus did not lose weight in the first five days post-infection but they all wasted during the three days. following. All died or had to be euthanized. Rodents infected with Omicron (BA.1), on the other hand, did not lose weight and none died.

XD is also found to have immune escape properties similar to that of the BA.1 Omicron subline.

For these two variants, one piece of data remains reassuring, despite their identification several weeks ago, epidemiologists have not observed an explosion in their prevalence.

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