Monday, June 13, 2022

ECDC: Implications of the Emergence and Spread of Omicron VOCs BA.4 and BA.5 for the EU/EEA


June 7th CDC Nowcast Of COVID Variants In the U.S. 


#16,818

Just shy of a month ago the ECDC Elevated Omicron BA.4 and BA.5 to VOC (Variants of Concern) status, and since then we've seen these new variant increase their presence both in Europe and in the United States (see CDC Nowcast: BA.4 & BA.5 Make Their First Appearance).

Their increased transmissibility over the already highly transmissible BA.1/BA.2 variants suggests there is little to stop these variants from becoming dominant globally over the next couple of months, likely supplanting older variants. 

Based on limited data, it doesn't appear that  BA.4 or BA.5 produce more severe illness than have BA.1/BA.2  (see SSI: Risk Assessment on BA.2.12.1, BA.4, and BA.5 Omicron Subvariants), but  their ability to evade prior immunity (either from vaccination or previous infection) may still drive hospitalization rates, ICU admissions, and deaths higher. 

Today the ECDC has published an epidemiological update which cautions member states to remain vigilant, and to prepare for an uncertain few months ahead.   I've only posted excerpts from the summary, so follow the link to read the report in its entirety. 


Implications of the emergence and spread of the SARS-CoV-2 variants of concern BA.4 and BA.5 for the EU/EEA
Epidemiological update
13 Jun 2022
 
Most European Union/European Economic Area (EU/EEA) countries have detected low proportions of the SARS-CoV-2 variants BA.4 and BA.5, however many have seen an increase in recent weeks. In Portugal, BA.5 has become the dominant SARS-CoV-2 variant and the increasing proportions of BA.5 have been accompanied by a surge in COVID-19 cases. The growth advantage reported for BA.4 and BA.5 suggest that these variants will become dominant throughout the EU/EEA, probably resulting in an increase in COVID-19 cases in coming weeks.

The extent of the increase in COVID-19 cases will depend on various factors, including immune protection against infection influenced by the timing and coverage of COVID-19 vaccination regimes, and the extent, timing and variant landscape of previous SARS-CoV-2 pandemic waves. Based on limited data, there is no evidence of BA.4 and BA.5 being associated with increased infection severity compared to the circulating variants BA.1 and BA.2. However, as in previous waves, an increase in COVID-19 cases overall can result in an increase in hospitalisations, ICU admissions and deaths.

Countries should remain vigilant for signals of BA.4 and BA.5 emergence and spread; maintain sensitive and representative testing and genomic surveillance with timely sequence reporting, and strengthen sentinel surveillance systems (primary care ILI/ARI and SARI). Countries should continue to monitor COVID-19 case rates - especially in people aged 65 and older - and severity indicators such as hospitalisations, ICU admissions, ICU occupancy and death.

Improving COVID-19 vaccine uptake of the primary course and first booster dose in populations who are yet to receive them remains a priority. It is expected that additional booster doses will be needed for those groups most at risk of severe disease, in anticipation of future waves.

Event background

The SARS-CoV-2 variants BA.4 and BA.5 were first detected in South Africa in January and February 2022, respectively. They became the dominant variants in that country in May 2022 [1] and a parallel increasing trend in epidemiological indicators, such as case notification rates and test positivity rates [2], suggested that these two variants were responsible for the surge in cases observed in South Africa in April−May 2022. As of 12 May 2022, ECDC reclassified Omicron sub-lineages BA.4 and BA.5 from variants of interest to variants of concern [3].

BA.4 and BA.5 are two sub-lineages of the Omicron clade (B.1.1.529). They share the same mutation profile in the spike gene, while they have different sets of mutations in their remaining genome. The defining mutations in the spike protein of BA.4 and BA.5 compared to BA.2 include Δ69-70, L452R, F486V and R493Q (reversion). Given the current epidemiological background where BA.2 is the dominant variant in the EU/EEA, laboratories can use the presence of the spike changes L452R or F486V or S-gene target failure [4] as a pre-screening for the variants. To be able to differentiate between BA.4 and BA.5, assays targeting discordant parts outside of the spike gene or whole genome sequencing (WGS) are required. Since BA.4 and BA.5 only emerged recently, it has not yet been possible to include the variants in a rapid antigen detection test (RADT) evaluation study.

There is currently no indication of any change in severity for BA.4 or BA.5 compared to previous Omicron lineages. Severity indicators in Portugal (hospitalisation, ICU admissions and deaths) as of 1 June are below the levels reached in the previous Omicron peak, however, week-on-week increases continue to be observed. Over the past six weeks, both hospitalisations and ICU admission increases have mainly been among those aged 60 years and above [5].

The current growth advantage for the BA.4 and BA.5 variants of concern (mainly observed in South Africa [4] and Portugal [6]) compared to the dominant variant BA.2, is probably due to their ability to evade immune protection against infection induced by prior infection and/or vaccination, particularly if this has waned over time. Based on preliminary in-vitro data from preprints, BA.4 and BA.5 are antigenically distant from the ancestral virus [7,8] and, compared to BA.1 and BA.2, they are less efficiently neutralised by sera from individuals vaccinated with three doses of COVID-19 vaccine (Vaxzevria or Comirnaty), or by sera from BA.1 vaccine breakthrough infections [8,9]. In addition, there has been an increased rate of re-infection in Portugal [5]. 
 
Overall, this raises concerns about more frequent BA.4/BA.5 vaccine breakthrough infections than for BA.1/BA.2, and for Omicron reinfections. Nevertheless, as of the end of week 22, 2022, overall transmission continues to decline in most EU/EEA countries, as shown by both overall case notification rates and case rates among people aged 65 years and above [10].

More evidence is needed to elucidate the efficiency of monoclonal antibodies (mAb) against the BA.4 and BA.5 variants, but evidence so far suggests that BA.4 and BA.5 have shown a reduced or broadly similar pattern of mAb sensitivity to that of BA.2 [7,11,12].

At present, there are no data available on vaccine effectiveness against different clinical outcomes for Omicron sub-lineages BA.4 and BA.5. Data on vaccine effectiveness against the Omicron variants BA.1 and BA.2 are described in a recently published ECDC technical report on the second mRNA COVID-19 vaccine booster dose [13].

(SNIP)

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