Further SARS-CoV-2 variants, and intermittent epidemics could become the 'new normal'

The outbreak of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic, which has claimed more than 6.4 million deaths to date. Despite strict efforts to limit transmission of the virus, SARS-CoV-2 has spread rapidly and mutated several times. This has led to the emergence of a new SARS-CoV-2 variant with higher transmissibility and immune evasion characteristics.

new Nature Communication The journal study explored the dynamics of Omicron SARS-CoV-2 and other variants circulating in the UK from 23 November 2021 onwards, when Omicron was first detected.

Study: Dynamics of the Rival SARS-Cov-2 Variant During the Omicron Epidemic in the UK. Image Credit: Mayboon / Shutterstock.com

introduction

The most recent SARS-CoV-2 concern variant (VOC) to be described is the Omicron variant (PANGO lineage B.1.1.529). This variant has multiple mutations in its spike protein, as well as other viral proteins.

For example, the Omicron variant has 15 mutations in the receptor binding domain (RBD), which binds to the host angiotensin-converting enzyme 2 (ACE2) receptor. This mutation alters the site at which the neutralizing antibody binds to RBD, thereby allowing Omicron to escape neutralization, even after vaccination or prior infection with the older SARS-CoV-2 variant.

The result has been increased rates of re-infection and breakthrough infection. However, with the decreasing test rate coupled with the currently available testing capacity at 100%, the true proportion of Omicron waves remains unknown.

To address this challenge, the current study uses data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, which is a cross-sectional testing study conducted in the UK.

Study findings

In the study sample, the prevalence of Omicron remained around 0.11% on 7 December 2022, which is about three weeks from the first confirmed case in the UK. Simultaneously, the Delta variant, which was the dominant circulating strain during the previous three months, had a prevalence of 1.3%.

The Omicron strain appears to be mainly imported from or exported to the United States, Germany, and France.

Around 50% of COVID-19 cases in the UK are caused by Omicron by the end of next week. As of December 23, 2021, 90% of cases are caused by Omicron.

As of February 14, 2022, Omicron is responsible for almost all cases. The last Delta-positive sample was also reported today.

Omicron cases increased by 0.2 per day from November 23, 2021 to March 1, 2022. On December 3, 2021, which is when the researchers of this study detected the first Omicron cases, the growth rate was 0.37. More than a month later, it was only 0.1.

This may be due to the lower generation time for the Omicron, which is estimated to be 28% less than the Delta variant. Higher rates of virus spread among younger, less vaccinated age groups who are also more sociable in social circles could also be a contributing factor.

By the end of 2021, approximately 7% of swabs were positive for Omicron; however, this prevalence decreased to less than 5% during January 2022. Then in the same month, the figure again increased to around 2.6% in early March 2022.

The reproduction rate (Rt) is about two on 17 December 2022, which is two weeks after the onset of the Omicron wave in the UK. Currently, 90% of those 12 years and older have been vaccinated with at least one dose of the COVID-19 vaccine, 82% with two doses and 53% with three doses.

Rt then decreases as social interaction decreases. By early January 2022, Rt was under one.

By the end of January 2022, Rt increased to more than one and then decreased throughout February; but tends to increase this month.

Although the recent infection rate is very high, the threshold of herd immunity required for prevalence reduction has not been reached.”

With regard to the general population, the prevalence of Omicron is increasing across the UK to over 7% in the North East of England. However, the prevalence is less than 4% in East England. London is associated with the earliest peak, which is likely because the Omicron was first introduced here.

Rt is highest in those between the ages of five and 17 in January 2022. In other age groups, Rt values ​​quickly fall below one.

Omicron prevalence peaked in this group on January 28, 2022, at nearly 11%. This compares to less than 8% as of January 1, 2022, for those between the ages of 18 and 34.

Individuals aged 55 years or older were associated with the lowest prevalence, which is consistent with high vaccination rates. However, the Rt value in this group increased on March 1, 2022 to 1.1.

This demonstrates the limited vaccine effectiveness of the COVID-19 vaccine against Omicron infection.”

a The prevalence of the Omicron and Delta variants of the SARS-CoV-2 model in the UK was estimated using the Bayesian P-spline mixed effects model. Prevalence estimates are indicated by center estimates (solid lines) and 95% credible intervals (shaded areas). Daily weighted estimates of the mean prevalence (points) are shown with 95% credible intervals (error bars). b The proportion of lineage models identified as Omicron in the UK, estimated using Bayesian logistic regression (red) and using a mixed-effect Bayesian P-spline model (blue). Estimates are displayed with center estimates (solid lines) and 95% credible intervals (shaded areas). Daily estimates of the average proportion of the Omicron lineage (points) are shown with 95% confidence intervals (error bars). c The daily growth rates of Omicron (purple), Delta (orange) and their additive differences (green) were estimated from the mixed effect Bayesian P-spline model. Estimates are displayed with center estimates (solid lines) and 95% credible intervals (shaded areas).

Sublineage Competition

Previous models have shown that the Omicron BA.1, BA.1.1, and BA.2 variants exhibit changing proportions over this period. Even as BA.2 increased, the prevalence of BA.1 decreased.

At the peak of the Omicron wave on December 30, 2021, BA.1 represented 85% of cases compared to 15% and 0.2% for BA.1.1 and BA.2, respectively.

This trend shifted just two months later, with the prevalence of BA.1 decreasing to less than 10% of cases, while BA.1.1 and BA.2 rose to more than 20% and almost 70%, respectively. This variant is responsible for the winter Omicron wave in the UK.

The daily growth rates of BA.2 and BA.1.1 are 0.133 and 0.42 times higher than BA.1, respectively, while BA.1 is 0.09 times higher than BA.1.1. Both variants are more infectious than BA.1, with BA.2 spreading at the fastest rate of these three Omicron subvariants.

BA.1.1 became dominant in some countries even before BA.1 established itself, thereby demonstrating its superior fit through a large number of beneficial mutations.

The Rt for BA.2 is 1.17 compared to 0.77 for the non-BA.2 Omikron variant on March 1, 2022. This supports the fitness of the BA.2 replica.

BA.2 was also associated with the most specific COVID-19 symptoms such as anosmia, ageusia, fever, and a new long-term cough in a higher proportion of patients compared to BA.1 infection.

Implication

The current study used high-quality REACT-1 data to estimate the prevalence of Omicron infection. The investigators also described exposure risk for Delta and Omicron infections, as well as BA.1, BA.1.1, and BA.2 separately.

The dynamics of these different variants have been reflected in different growth rates and prevalence over time, rather than treating all of them as a single variant.

Further studies need to examine whether different lineages and sublineages have different cycle thresholds (Ct) for detection, which may alter the observed prevalence. Nonetheless, research findings suggest that SARS-CoV-2 will reach a new level of fitness through the development of mutations that enhance its immune escape characteristics.

“Assuming the emergence of further divergent variants, intermittent epidemics of the same magnitude [as Omicron, which reached a record prevalence of 7% in England at one point] may become the ‘new normal’.”

Booster vaccine doses and improvements to the current COVID-19 vaccine to provide immunity to this newer variant, as well as ongoing monitoring, will be critical to maintaining public health.

Journal reference:

• Eales, O., de Oliveira Martins, L., Page, AJ, et al. (2022). Dynamics of the Rival SARS-Cov-2 Variant During the Omicron Epidemic in the UK. Nature Communication. doi:10.1038/s41467-022-32096-4.

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