Study: Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients. Image Credit: Naeblys/Shutterstock

The seroprevalence study shows that vaccination can increase impaired humoral immunity against the Omicron BQ.1.1 subvariant.

In a recently published study, medRxiv* presenter, researchers conducted a multicenter, cross-sectional study of seroprevalence in the emergency departments of five hospitals in North Rhine-Westphalia, Germany, between August and September 2022. Wu01, BA.4/5 and BQ.1.1.

Studies: Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients. Image Credit: Naeblys/Shutterstock


Among these three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, BA.5 exhibited the strongest immune escape from antibodies induced by previous infection, vaccination, and therapeutic monoclonal antibodies. However, the continued evolution of Omicron has resulted in the emergence of the BQ.1.1 and BQ.1 sublineages with even greater potential for immune hijacking, primarily attributed to N460K mutations. These subvariants, BQ.1.1 and BQ.1, had a relative share of 49.7% of the worldwide whole-genome sequenced SARS-CoV-2 variants, as of November 2022, enabling infections in SARS-CoV-2 recovered and vaccinated individuals.


Three years after the emergence of SARS-CoV-2, immunity avoidance poses the biggest challenge in tackling the 2019 coronavirus disease (COVID-19). In this context, comprehensive knowledge of population immunity against SARS-CoV-2 will be crucial as it will help determine the future course of the pandemic.

about the study

In this multicenter study, the researchers first collected blood serum samples from all 1411 participants. Wu01 used enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA) to determine spike (S) and nucleocapsid (NC) immunoglobulin G (IgG) levels against BA.4, BA.5 and BQ.1.1. Additionally, they measured serum neutralization against these three variants using pseudovirus neutralization assays.

In addition, the researchers combined S & NC-IgG activity and neutralization activity data with participants’ epidemiological and clinical data. Additionally, they extracted comprehensive information about each participant’s SARS-CoV-2 immunity and case history through structured interviews and scanning of their medical records.

Finally, the team performed multivariate and Bayesian network analysis to gain insights into the factors that determine the quality and quantification of the anti-SARS-CoV-2 antibody response. Serum minimum infectious dose (ID50s) > 10 showed detectable serum neutralization among study participants. The researchers correlated all participants’ S-IgG values ​​with detectable S-IgG versus ID.fifty Values ​​of all participants with detectable serum neutralization against Wu01 and BA.4/5.

Study findings

The mean age of enrollees was 53, with 48.5% and 51.3% male and female, respectively. More than 64% of the participants had pre-existing health conditions such as cardiovascular and neoplastic diseases, and 13.6% reported drug immunosuppression. By age classification, 67.7% of study participants were vaccinated, 94.4% received at least one dose of vaccine according to German COVID-19 vaccination recommendations, and 45.7% had at least one previous SARS-CoV-2 had the infection. Therefore, close to 51% of the participants had previous exposure to minimal S-antigen exposure from vaccination or infection.

The researchers detected S-IgG in 95.6% of study participants, with not much difference between men and women in age groups. Conversely, 4.4% of the participants were S-IgG negative and 86.9% of these were immunocompromised or inadequately vaccinated. However, S-IgG levels were lower in drug immunocompromised participants. Notably, S-IgG levels increased with S-antigen contacts, vaccines, and previous infections, plus NC-IgG serostatus significantly affected S-IgG levels.

Study analysis showed that S-IgG levels best predicted neutralization activity versus BQ.1.1. However, 59.6% of individuals with detectable S-IgG levels above 1000 binding antibody units (BAU)/ml showed no significant neutralizing activity against BQ.1.1. He stressed that low S-IgG levels are insufficient for an accurate assessment of neutralization activity against BQ.1.1. Furthermore, the 23-fold reduction in serum neutralizing activity against BQ.1.1 relative to strain Wu01 highlighted that this variant has the highest immunity-evasion potential to date. This information can help assess the risk of COVID-19 from emerging SARS-CoV-2 Omicron variants. It can also inform Omicron about vaccination strategies, facemask requirements and further intervention strategies for adapted vaccines.

Most importantly, the study results confirmed that vaccines represent a better future strategy to boost immunity in high-risk populations because the timing and outcome of previous infection-induced immunity is unpredictable.


To summarize, this is one of the pioneering studies evaluating immune evasions of BA.4/5 and BQ.1.1 Omicron subvariants in real-world settings. The authors found that despite high S-IgG seroprevalence among study participants, they only moderately adhered to vaccination recommendations. Subsequently, serum neutralizing activity against BQ.1.1 remained below satisfactory levels. However, the study results highlighted that during waves of COVID-19 caused by variants of SARS-CoV-2 such as BQ.1.1, vaccine uptake by all individuals at high risk will be critical in reducing the risk of serious consequences.

*Important warning

medRxiv publishes preliminary scientific reports that have not undergone peer review and should therefore not be considered conclusive, guiding clinical practice/health-related behavior, or considered established knowledge.

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