COVID-19 News: Study From Netherlands Shows That BA.4/BA.5 Variants And Sub-lineages Are More Immune Evasive Than BA.2 And Its Sub-lineages

COVID-19 News: Despite claims by certain European/American virologist and variant trackers that the BA.2 variant and its sub-lineages are more immune evasive, researchers from the Netherlands in a new study have found that the BA.4/BA.5 variants and sub-lineages are more immune evasive and are able to easily cause breakthrough infections in those with prior exposure to the Omicron BA.1 variant.


 
The study was conducted by scientists from:
 
-The Center for Infectious Disease Control, WHO COVID-19 reference laboratory, National Institute for Public Health and the Environment (RIVM)-Netherlands
 
-The Department of Medical Microbiology, University Medical Center Utrecht, Utrecht-Netherlands
 
-The Saltro Diagnostic Center for Primary Care, Utrecht-Netherlands
 
The study team investigated whether previous infection and/or vaccination against SARS-CoV-2 provides different protection against a new infection with the Omicron BA.4/5 or BA.2 variant.
 
The study findings showed that previous SARS-CoV-2 infection protected better against infection with the BA.2 than the BA.4/5 variant.
 
Worryingly, this indicates that BA.4/5 is better at evading infection-induced immunity.
 
Different immune evasion by variants within the Omicron lineage allows for repeated SARS-CoV-2 Omicron infections to occur. Such studies about immune evasion of current and novel virus variants are informative for developing updated vaccines.
 
The study findings were published in the peer reviewed journal: Eurosurveillance.
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.7.2200724
 
Thailand Medical News already in our previous COVID-19 News coverages have been warning that despite the current onslaught by the various XBB sub-lineages and also other recombinant variants and also the BA.2 derivative sub-lineages CH.1.1, expect the BA.5 subvariants and sub-lineages to make a return with more virulent and pathogenic versions in the next onslaught!
https://www.thailandmedical.news/news/covid-19-news-variant-hunters-say-that-the-ba-5-sub-lineages-are-receding,-being-replaced-by-ba-2-sub-lineages-and-various-recombinants-we-say-no
 
https://www.thailandmedical.news/news/sars-cov-2-research-analysis-of-gibbs-energy-potential-in-newly-emerged-ba-5-2-and-bf-7-sub-lineages-in-china-suggest-that-they-are-more-infective
 
ht tps://www.thailandmedical.news/news/covid-19-news-new-ba-5-sublineages-continue-to-emerge-globally-as-virus-evolves-rapidly--new-dy-1-variant-emerges-in-china-ba-5-2-48-with-sa570s
 
https://www.thailandmedical.news/news/covid-19-news-china-s-bf-7-14-spawns-new-bf-7-14-1-sublineage--newer-more-immune-evasive-ba-5-sublineages-will-lead-the-next-reinfection-onslaughts
 
https://www.thailandmedical.news/news/covid-19-news-east-asian-variants-bf-7-14,-bf-7-15,-bf-5-2,-ba-5-2-48,-ba-5-2-49--ba-5-2-50-continue-to-wreak-havoc-in-china-and-japan-deaths-rising
 
https://www.thailandmedical.news/news/covid-19-news-stupids-saying-that-china-variants-have-been-circulating-before-bf-7-14,-ba-5-2-48,-ba-5-2-49-are-new,-past-exposure-to-ba-5-will-not-he
 
https://www.thailandmedical.news/news/covid-19-news-xbb-1-5-variant-which-is-more-transmissible-and-spreading-fast-will-not-wreak-much-havoc-as-compared-to-new-bf-and-ba-5-2-sublineages
 
https://www.thailandmedical.news/news/covid-19-news-china-s-covid-19-crisis-is-going-to-hit-the-west-hard-travel-restrictions-are-not-enough-total-global-travel-ban-needed-for-4-months
 
The Omicron variant is constantly evolving to give rise to novel sub-VOCs with greater transmissibility and immune evasiveness, making COVID-19 mitigation a challenging task. Varying immune-evasiveness of Omicron sub-VOCs allows the occurrence of novel SARS-CoV-2 infections.
 
Detailed analysis of immune escape of vaccination or infection-induced immune protection by novel VOCs and sub-VOCs could inform policy-making and guide the development of updated (COVID-19) vaccines.
 
A SARS-CoV-2 infection-only method was used to evaluate the impact of prior anti-SARS-CoV-2 immunity levels against novel BA.4/5 and BA.2 infections between May 2 and July 24, 2022.
 
The study team additionally evaluated the effects of the VOC-wise duration between the prior and current case of COVID-19 and that of different VOC infections on the development of Omicron BA.4/5 and Omicron BA.2 infections.
 
The SARS-CoV-2 spike (S) gene target failure (SGTF) was assessed using SARS-CoV-2-positive tests among community-dwelling individuals based on the reverse transcription-polymerase chain reaction (RT-PCR) results for SARS-CoV-2 S, open reading frame 1ab (ORF1ab) and nucleocapsid (N) genes. RT-PCR reports and national-level SARS-CoV-2 testing register data were linked for the analysis.
 
The register comprised data on individual demographic parameters and the self-documented status of COVID-19 vaccination.
 
Only individuals with prior SARS-CoV-2 infection ≥30 days prior to the current SARS-CoV-2 infection were included.
 
Comprehensive whole genome sequencing (WGS) was performed using SGTF samples to determine the causative variant among 7.3% (117 out of 1,609) prior infections with VOC data.
 
However, for the remaining 93% (1,492 samples), the VOC was determined based on SGTF results and the date of SARS-CoV-2 testing. Logistic regression modeling was performed, and the adjusted odds ratios (aOR) were calculated, with data adjustments for the week of SARS-CoV-2 testing, sex, and age.
 
It was found that during the study period, 26 % (n=7,052) of BA.2 infections and 74% (n=19,836) of BA.4/5 infections were identified.
 
Interestingly, during the initial and last weeks, Omicron BA.4/5 caused 3.30% (18 out of 545) infections and 99% (2,543 out of 2,572) infections. BA.4/5-infected individuals were usually younger compared to BA.2-infected individuals.
 
It was also found that the fraction of individuals with current SARS-CoV-2 infections was more significant for Omicron BA.4/5 infections, weekly and during the entire study period.
 
The study found that out of 9,836 cases of BA.4/5 infections, 31% (n=6,215) of individuals had prior COVID-19 history than 20% (1,408 out of 7,052) of Omicron BA.2-infected individuals.
 
Similar results were obtained in the adjusted analyses, with aOR values of 1.4 and 1.6 among unvaccinated and vaccinated cases, respectively.
 
It was also found that among individuals without prior COVID-19 history, no significant association was observed between the status of vaccination and Omicron BA.4/5 versus BA.2 infections (aOR values of 1.1 and 1.1 for primary vaccination and booster vaccination, respectively).
 
Importantly, prior COVID-19 history enhanced the risk of BA.4/5 infections, compared with Omicron BA.2 infections (aOR 1.4). Among previously infected individuals, the duration between SARS-CoV-2 infections was shorted among BA.4/5-infected individuals than BA.2-infected individuals, with median intervals of 182 days versus 206 days, respectively).
 
The study also showed that prior Omicron BA.1 infection history was more prevalent among BA.4/5-infected individuals (63%) than BA.2-infected individuals (44%).
 
The study findings indicated that Omicron BA.4/5 has a greater capacity to evade BA.1 infection-conferred immune protection than with other VOC-caused prior SARS-CoV-2 infections.
 
Significantly, Omicron BA.1 infection showed associations with Omicron BA.4/5 infections instead of BA.2 infections (aOR of 1.9).
 
For prior infections with other VOCs, except Omicron BA.2, Omicron BA.4/5 infection risks were again more significant compared to the risk of Omicron BA.2 infections.
 
The complete case analysis yielded similar findings, excluding COVID-19 cases lacking vaccination data from prior SARS-CoV-2 infection analysis.
 
The study findings showed that among 385 samples sequenced by SGTF, WGS verified 14% (n=52) Omicron BA.4 infection cases and 84% (n=322) Omicron BA.5 infection cases [positive predictive value (PPV) of 97.0% (n=374) of the SGTF analysis for detecting Omicron BA.4/5]. Among SGTF-sequenced samples, the percentage of Omicron BA.5 infections increased as time passed. Non-SGTF findings strongly correlate with Omicron BA.2 and a 98.0% PPV (485 out of 495 cases).
 
For the study, pre-VOC period was defined as that between January 18 (initiation of data retrieval) and February 17, 2021, by non-SGTF analysis. The Alpha wave was considered between January 18 and September 27, 2021, by SGTF analysis. The Delta wave was considered between June 20, 2021, and January 7, 2022, by non-SGTF analysis. BA.1 wave was considered between November 23, 2021, and April 9, 2022, by SGTF analysis, and that of BA.2 between January 29, 2022, and the end of the study period by non-SGTF analysis.
 
The study findings showed that prior SARS-CoV-2 infection-induced immunity conferred more significant protection against Omicron BA.2 infections than Omicron BA.4/5 infections, indicating that the BA.4/5 sub-VOC had a greater capacity to evade prior COVID-19-induced immunity.
 
It will be interesting to see how the next generation of BA.5 sub-lineages behave in the next onslaught as we predict an anomaly will be seen that has never been exhibited in the history of immunology or virology!
 
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