Impact of the emergence and spread of SARS-CoV-2 mutants BA.4 and BA.5 of concern in the EU / EEA

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 predominant subspecies of the country in May 2022 [1] Parallel increasing trends in epidemiological indicators such as case notification rate and positive test rate [2]Suggested that these two variants were responsible for the surge in cases observed in South Africa from April to May 2022. [3]..

BA.4 and BA.5 are two sub-strains of Omicron Clade (B.1.1.529). They share the same mutation profile in the spike gene, but the rest of the genome has a different set of mutations. Clear mutations in BA.4 and BA.5 peplomer compared to BA.2 include Δ69-70, L452R, F486V, and R493Q (return). Given the current epidemiological background in which BA.2 is a major variant of the EU / EEA, laboratories can use the presence of spike-altered L452R or F486V or S gene targeting disorders. [4] As a variant pre-screening. To be able to distinguish between BA.4 and BA.5, an assay targeting the outer discrepancy of the spike gene or whole genome sequence (WGS) is required. Due to the recent appearance of BA.4 and BA.5, it has not yet been possible to include variants in the Rapid Antigen Detection Test (RADT) evaluation study.

Currently, there are no signs of change in BA.4 or BA.5 severity compared to previous Omicron strains. As of June 1, Portugal’s severity indicators (hospitalization, ICU admission, death) are below the levels reached at the previous Omicron peak, but weekly increases are still being observed. Over the last 6 weeks, increased hospitalizations and ICU admissions have been seen primarily among people over the age of 60. [5]..

Current growth benefits of the BA.4 and BA.5 mutants of concern (mainly observed in South Africa) [4] And Portugal [6]) Compared to the predominant mutant BA.2, this is probably due to the ability to evade immune defense against previous infections and / or vaccination-induced infections if this declines over time. Based on preliminary in vitro data from the preprint, BA.4 and BA.5 are antigenically distant from the ancestral virus. [7,8] Also, compared to BA.1 and BA.2, the efficiency of neutralization by serum from individuals who received the COVID-19 vaccine (Vaxzevria or Comirnaty) three times or by breakthrough infection of the BA.1 vaccine was lower. increase. [8,9].. In addition, reinfection rates are increasing in Portugal. [5].. Overall, this raises concerns about more frequent breakthrough infections of the BA.4 / BA.5 vaccine than BA.1 / BA.2 and Omicron reinfections. Nonetheless, as of the end of the 22nd week of 2022, overall in most EU / EEA countries, as shown by both the overall case notification rate and the case rate for people over the age of 65. Infections continue to decline. [10]..

More evidence is needed to elucidate the efficiency of monoclonal antibodies (mAbs) against BA.4 and BA.5 variants, but the evidence so far is that BA.4 and BA.5 have a pattern of mAb sensitivity. It suggests that it shows a decline or near similarity. That of BA.2. [7,11,12]..

Currently, there are no data on vaccine efficacy for various clinical outcomes of the Omicron substrains BA.4 and BA.5. Data on vaccine efficacy against the Omicron mutants BA.1 and BA.2 can be found in the recently published ECCC technical report on the second mRNA COVID-19 vaccine booster dose. [13]..

EU / EEA BA.4 and BA.5: Updated as of June 13, 2022

BA.4 and BA.5 were first detected in the EU / EEA in March 2022. Portugal first observed a significant increase in cases in the EU / EEA, with an increase in the proportion of either of these two variants (BA.5). As of May 30, 2022, BA.5 is the leading SARS-CoV-2 variant in Portugal with an estimated ratio of approximately 87%. [6,14].. Between the 19th and 20th weeks of 2022, the number of cases in Portugal decreased and stabilized. This indicates that the peak of the BA.5 wave in Portugal may have been reached. Increased rates of BA.4 and BA.5 infections in many EU / EEA countries over the last few weeks (17-21 weeks of 2022), including Austria, Belgium, Denmark, France, Germany, Ireland, Italy and the Netherlands. Was observed. , Spain, Sweden [15,16]..

In Belgium, in particular, BA.5 reached an estimated rate of 19% and BA.4 accounted for 7.5% of the genome sequenced between 21 and 22 weeks. In Spain, BA.4 and BA.5 accounted for more than 10% of the samples analyzed by variant-specific PCR in 10 autonomous states between 21 and 22 weeks, with significant variability among communities. In the Netherlands, BA.5 reached a rate of 8% at week 20, while BA.4 was detected at a rate close to 5%.

The growth benefits reported for BA.4 and BA.5 suggest that these variants will predominate across the EU / EEA and will probably increase cases of COVID-19 in the coming weeks. The extent of the increase depends on a variety of factors, including immune protection against infections affected by the timing and scope of the COVID-19 vaccination program, and the range, timing, and atypical conditions of previous SARS-CoV-2 pandemic waves. it’s different. Based on limited data, there is no evidence that BA.4 and BA.5 are associated with increased infection severity compared to the circulating mutants BA.1 and BA.2. However, as in the previous wave, more cases of COVID-19 may lead to more hospitalizations, ICU admissions, and deaths.

Monitoring and reporting

The ECDC encourages countries to remain vigilant for signs of the emergence of BA.4 and BA.5. Sensitive and representative testing strategies and genomic surveillance to accurately determine to some extent that these mutations may contribute to the observed increase in severe outcomes in the population (eg, increased hospital or ICU admission). Is required.

Therefore, countries need to strengthen their sentinel systems (primary care ILI / ARI and SARI) and continue to collect laboratory-identified cases (from sites other than sentinel) and data on hospitalization / ICU admission and bed occupancy. I have. [17].. Countries need to be vigilant and scale up their tests and sequences as needed.Countries need to continue to sequence positive samples and share sequence data in a timely manner. [18,19].. The SARS-CoV-2 consensus sequence should be stored in the GISAID database, and if possible, the raw data of the SARS-CoV-2 sequence should be stored in the COVID-19 data portal through the European Nucleotide Archive (ENA). .. [20].. If possible, antigen characterization should be done. This contributes to an understanding of the characteristics of these variants, and specimens / isolates can also be shared for characterization with the WHO Reference Lab. [21]..

Minimal metadata should be reported to the TESSy case-based record type NCOV or to the NCOV Variant in aggregated format and, if possible, the GISAID accession number of the sequenced case. there is. ECDC is for designated users in each country EpiPulse events at BA.4 and BA.5 Informally discuss and share information about these two variants, especially the characteristics of the virus and evidence of varying severity of the disease, viral infectivity, antigenic escape, and diagnostic and therapeutic implications.

vaccination

Improving primary course COVID-19 vaccine uptake and initial booster doses in the population to reduce the burden of COVID-19 hospitalization and mortality remains a priority for all age groups. For more information on the dose and vaccine intake of the COVID-19 vaccine administered, please see ECDC Vaccine Tracker [22]..

Depending on evolving epidemiology, data on vaccine efficacy over time, and other factors such as seasonality, the timing and population recommendations that may benefit from additional booster immunization need to be reassessed. I have.

Public health benefits of administering a second mRNA COVID-19 booster dose Recently evaluated by the ECDC to be most pronounced in people over the age of 80, a second booster immunization in this population was found to be optimal in situations where viral circulation is high or increased.Mathematical modeling also suggests that the second booster deployment, including immunocompetent 60-79 years in the EU / EEA, is probably beneficial in avoiding death, but of the rollout. The optimal timing is uncertain and for future waves [13]..

In anticipation of future waves, or prior to the fall / winter season, additional booster immunization is the group with the highest risk of the most serious illness (eg, adults over 60 years and the medically vulnerable population). ) Is expected to be necessary for rapid deployment. These additional doses are close to the period when increased viral circulation is expected, but have the greatest effect if administered before reaching high levels.