Saturday, April 22, 2023

WHO Initial Risk Assessment On VOI XBB.1.16

Regions with Increasing COVID (in red) - Credit WHO Epi Rpt #139


While the United States, Canada, and much of Europe continue to report steady or falling COVID cases, the latest WHO report shows sharp increases in Southeast Asia (↑ 654%) and the Eastern Mediterranean ( 96%) over the past 28 days (despite limited and often sporadic reporting). 

Some of this surge is believed due to the emerging XBB.1.16 variant - which we've been monitoring for several weeks (see here, here, and here) - and which was elevated to a VOI (Variant of Interest) this past week by the WHO (see statement below).

WHO is currently tracking two variants of interest (VOIs): XBB.1.5 and XBB.1.16.

On 17 April 2023, following a meeting of the Technical Advisory Group on Virus Evolution (TAG-VE), XBB.1.16 was added to the WHO list of VOIs. XBB.1.16 is a descendent lineage of XBB, which is a recombinant of two BA.2 descendent lineages. This variant was first reported in January 2023 and added to the WHO list of variants under monitoring (VUMs) on 22 March 2023.

Additionally, WHO is tracking six VUMs and their descendent lineages, namely BA.2.75, CH.1.1, BQ.1, XBB, XBB.1.9.1 and XBF.

Globally, XBB.1.5 has been reported from 96 countries. In epidemiological week 13 (27 March to 2 April 2023), XBB.1.5 accounted for 50.8% of sequences, which is an increase from 46.2% in week 9 (27 February to 5 March 2023). 

XBB.1.16 has been reported in 31 countries. In week 13, XBB.1.16 accounted for 4.2% of submitted sequences, which is up from 0.5% in week 9. The prevalence of XBB.1.16 is estimated from GISAID data using specific lineage-identifying nucleotide substitutions (T12730A, T28297C, and A28447G).

Due to its estimated growth advantage and immune escape characteristics, XBB.1.16 may spread globally and contribute to an increase in case incidence. However, at present, there is no early signal of an increase in severity

The initial XBB.1.16 risk assessment is ongoing and is expected to be published in the coming days.

Yesterday the WHO's COVID-19 Technical Lead Maria Van Kerkhove announced the publication of the initial risk assessment (see below) on twitter.  For now, the WHO considers the global risk assessment for XBB.1.16 to be low compared to XBB.1.5, although that could change over time. 

I'll have a brief postscript after the break. 

XBB.1.16 Initial Risk Assessment, 17 April 2023

XBB.1.16 is a descendent lineage of XBB, a recombinant of two BA.2 descendent lineages. XBB.1.16 was first reported on 09 January 2023, and designated a variant under monitoring (VUM) on 22 March 2023. On 17 April 2023, XBB.1.16 was designated a variant of interest (VOI). XBB.1.16 has a similar genetic profile as the VOI XBB.1.5, with the additional E180V and K478R amino acid mutations in the spike protein compared to their parent XBB.1.

As of 17 April 2023, 3648 sequences of the Omicron XBB.1.16 variant have been reported from 33 countries (GISAID, XBB.1.16 searched using variant defining nucleotide mutations T12730A, T28297C, A28447G). The majority of the XBB.1.16 sequences are from India (63.4%, 2314 sequences). The other countries with at least 50 sequences include the United States of America (10.9%, 396 sequences), Singapore (6.9%, 250 sequences), Australia (3.9%, 143 sequences), Canada (2.6%, 94 sequences), Brunei (2.4%, 89 sequences), Japan (2.0%, 73 sequences) and the United Kingdom (2.1%, 75 sequences).

Globally, there has been a weekly rise in the prevalence of XBB.1.16. During epidemiological week 13 (27 March to 2 April 2023), the global prevalence of XBB.1.16 was 4.15%, an increase from 4 weeks prior (epidemiological week 9, 27 February to 5 March 2023), when the global prevalence was 0.52%.

Following a sustained increase in the prevalence of XBB.1.16 and sustained growth advantage reported from several countries, and following the advice of the WHO Technical Advisory Group on SARS-CoV-2 Viral Evolution (TAG-VE) on a meeting convened on 17 April 2023, XBB.1.16 has been designated as a VOI.

The global risk assessment for XBB.1.16 is low as compared to XBB.1.5 and the other currently circulating variants, at this current time and with available evidence (see risk assessment table below). While growth advantage and immune escape properties are observed in different countries and immune backgrounds, including in countries where XBB.1.5 has become the dominant variant recently, no changes in severity have been reported in countries where XBB.1.16 are reported to be circulating. In India and Indonesia, there has been a slight increase in bed occupancy numbers. However, the levels are much lower than seen in previous variant waves.

Taken together, available information does not suggest that XBB.1.16 has additional public health risk relative to XBB.1.5 and the other currently circulating Omicron descendent lineages. However, XBB.1.16 may become dominant in some countries and cause a rise in case incidence due to its growth advantage and immune escape characteristics.

WHO and its Technical Advisory Group on SARS-CoV-2 Evolution (TAG-VE) continue to recommend Member States prioritize the following studies to better address uncertainties relating to antibody escape, and severity of XBB.1.16. The suggested timelines are estimates and will vary from one country to another based on national capacities:

• Share information on growth advantage for XBB.1.16 in your country and/or share sequence information (1-4 weeks)

• Neutralization assays using human sera, representative of the affected community(ies), and live XBB.1.16 virus isolates (2-4 weeks, see below table for results of studies that were performed so far)

• Comparative assessment to detect changes in rolling or ad hoc indicators of severity (4-12 weeks, see below table for results of studies that were performed)

The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continues to regularly assess the impact of variants on the performance of COVID-19 vaccines to inform decisions on updates to vaccine composition.(1)

The risk assessment below is based on currently available evidence and will be revised regularly as more evidence and data from additional countries become available. 



* Growth advantage 

Level of risk: Moderate, as since the first report of the emergence of XBB.1.16 on 09 January 2023, more than 3 months since, the variant has not led to a global sweep as some previous variants did. However, if the estimated growth rates are sustained, this variant may become the dominant variant in more countries and even globally over time. 

Confidence: High, as the growth advantage has been estimated by several groups of experts and in several countries and WHO regions.

 ** Antibody escape 

Level of risk: Moderate, due to a similar immune evasion profile as XBB.1.5, the current dominant variant globally.

Confidence: Low, as immune escape results are based on work from one laboratory. Additional laboratory studies would be needed to further assess the risk of antibody escape.

*** Severity and clinical considerations 

Level of risk: Low, as three months into the emergence of XBB.1.16, and from sustained and detailed variant and epidemiological surveillance in India, severity indicators have not increased across the Indian states, and neither are there any reports of severity in any of the other countries that have detected XBB.1.16. 

Confidence: Moderate, as there is regular coordination and data sharing with all WHO Regional colleagues, countries and partners continue, and as such we continue to receive early signals from countries if and when severity is rising.

As we've discussed often over the past year, the quality of surveillance and the frequency of reporting on COVID has fallen dramatically, with many countries - due to economic, political, or societal reasons - choosing not to report anything all.  

In their most recent weekly epi report, the WHO states:

  • Globally, during the past 28 days, 52 (22%) countries reported data to WHO on new hospitalizations at least once.
  • Across the six WHO regions, in the past 28 days, a total of 38 (16%) countries reported data to WHO on new ICU admissions at least once.

Put less diplomatically, it means that roughly 80% of the world's countries did not report even once over the past 28 days. Even in countries that do report, testing has become increasingly rare, and COVID-linked deaths are very likely being under reported. 

The WHO adds this disclaimer to their weekly reports:

Reported COVID-19 cases are underestimates as shown by prevalence surveys. 1–4 This is partly due to the reductions in testing and delays in reporting in many countries. Data presented in this report are therefore incomplete and should be interpreted with caution. Additionally, data from previous weeks are continuously being updated to incorporate retrospective changes in reported COVID-19 cases and deaths made by countries.

Sadly this `Don't test, don't tell' strategy extends far beyond COVID, and our visibility of MERS-CoV, avian flu, and many other emerging infectious diseases is similarly limited (see Flying Blind In The Viral Storm).

For more on this threat to global security, you may wish to revisit: