The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the coronavirus disease 2019 (COVID-19) pandemic, which has claimed more than 6.4 million lives so far. Despite strict efforts to limit viral transmission, SARS-CoV-2 has spread rapidly and mutated several times. This has led to the emergence of new SARS-CoV-2 variants with enhanced transmissibility and immune evasion characteristics.
A new study in the journal Nature Communications explores the dynamics of SARS-CoV-2 Omicron and other variants circulating in England from November 23, 2021, when Omicron was first detected.
Study: Dynamics of competing SARS-Cov-2 variants during the Omicron epidemic in England. Image credit: Mayboon / Shutterstock.com
Introduction
The most recently described SARS-CoV-2 variant of concern (VOC) is the Omicron variant (PANGO lineage B.1.1.529). This variant has many mutations in its spike protein, as well as other viral proteins.
For example, the Omicron variant has 15 mutations in its receptor-binding domain (RBD), which binds to the host angiotensin-converting enzyme 2 (ACE2) receptor. These mutations alter the sites where neutralizing antibodies bind to the RBD, subsequently allowing Omicron to escape neutralization, even after vaccination or prior infection with ancient variants of SARS-CoV-2.
The result has been increased rates of reinfections and new infections. However, with testing rates declining along with available testing capacity currently sitting at 100%, the true proportions of the Omicron wave remain unknown.
To overcome this challenge, the current study used data from the REACT-1 (Real-time Assessment of Community Transmission-1) study, which is a cross-sectional trial study conducted in England.
Results of the study
In the study samples, the prevalence of Omicron remained at around 0.11% on 7 December 2022, which was about three weeks since the first confirmed case in England. Simultaneously, the Delta variant, which was the dominant circulating strain during the previous three months, had a prevalence of 1.3%.
Omicron strains appeared to be primarily imported or exported to the United States, Germany, and France.
Around 50% of COVID-19 cases in England were caused by Omicron by the end of next week. As of December 23, 2021, 90% of cases were due to Omicron.
As of February 14, 2022, Omicron was responsible for almost all cases. The latest positive Delta sample was also reported today.
Omicron cases increased to 0.2 per day from November 23, 2021 to March 1, 2022. On December 3, 2021, which is when the researchers in this study detected the first case of ‘Omicron, the growth rate was 0.37. Just over a month later, it was only 0.1.
This could be due to Omicron’s shorter generation time, which is estimated to be 28% less than that of the Delta variant. The higher rate of viral spread among younger, less vaccinated age groups who also mix more in social circles could also be a contributing factor.
By the end of 2021, about 7% of swabs were positive for Omicron; however, this prevalence decreased to less than 5% during January 2022. Later that month, the rate increased again to 2.6% in early March 2022.
The reproductive number (Rt) was about two on 17 December 2022, two weeks after the start of the Omicron wave in the UK. At this time, 90% of those 12 years and older had been vaccinated with at least one dose of a COVID-19 vaccine, 82% with two doses, and 53% with three doses.
Rt subsequently decreased as social interactions decreased. In early January 2022, the Rt was below one.
At the end of January 2022, Rt increased to more than one and then decreased throughout February; however, it tended to increase during this month.
Despite the significantly high levels of recent infections, the herd immunity threshold needed to reduce prevalence had not yet been reached.”
In terms of the general population, the prevalence of Omicron increased across England to over 7% in North East England. However, its prevalence was less than 4% in the East of England. London was associated with the earliest peak, probably because Omicron was first introduced here.
Rt was highest between five and 17-year-olds in January 2022. In other age groups, the value of Rt dropped rapidly below one.
Omicron prevalence peaked in this group on January 28, 2022, at nearly 11%. This was compared to less than 8% on January 1, 2022, among 18- to 34-year-olds.
People aged 55 years and older were associated with the lowest prevalence, which is consistent with their high vaccination rates. However, the Rt value of this group increased on March 1, 2022 to 1.1.
This demonstrates the limited effectiveness of COVID-19 vaccines against Omicron infection.”
a Modeled prevalence of Omicron and Delta variants of SARS-CoV-2 in England estimated using a mixed-effects Bayesian P-spline model. Prevalence estimates are shown with central estimate (solid line) and 95% credible intervals (shaded region). Daily weighted estimates of mean prevalence (points) are shown with 95% credible intervals (error bars). b Modeled proportions of lineages identified as Omicron in England, estimated using Bayesian logistic regression (red) and using a mixed-effects Bayesian P-spline model (blue). Estimates are shown with central estimate (solid line) and 95% credible intervals (shaded region). Daily estimates of the mean proportion of Omicron lineages (dots) are shown with 95% confidence intervals (error bars). c Daily growth rate of Omicron (purple), Delta (orange) and their additive difference (green) estimated from the mixed-effects Bayesian P-spline model. Estimates are shown with central estimate (solid line) and 95% credible intervals (shaded region).
Underlining contest
Previous models have shown that the Omicron variants BA.1, BA.1.1 and BA.2 showed changing proportions during this period. Although BA.2 increased, the prevalence of BA.1 decreased.
At the peak of the Omicron wave on December 30, 2021, BA.1 accounted for 85% of cases compared to 15% and 0.2% for BA.1.1 and BA.2, respectively.
This trend changed just two months later, with BA.1 prevalence decreasing to less than 10% of cases, while BA.1.1 and BA.2 increased to 20% and almost 70%, respectively . These variants were responsible for the winter Omicron wave in England.
The daily growth rate of BA.2 and BA.1.1 was 0.133 and 0.42 times higher than that of BA.1, respectively, while BA.1 was 0.09 times higher than BA.1.1. Both variants are more transmissible than BA.1, with BA.2 spreading at the fastest rate of these three Omicron subvariants.
BA.1.1 became dominant in some countries before BA.1 was even established, thus indicating its superior fitness through a greater number of beneficial mutations.
The Rt of BA.2 was 1.17 compared to 0.77 for non-BA.2 Omicron variants on March 1, 2022. This supports the replicative fitness of BA.2.
BA.2 is also associated with the more specific symptoms of COVID-19, such as anosmia, ageusia, fever and new long-term cough in a higher proportion of patients compared to BA.1 infections.
Implications
The current study used high-quality REACT-1 data to estimate the prevalence of Omicron infections. The researchers also describe the risk of exposure for Delta and Omicron infections, as well as for BA.1, BA.1.1, and BA.2 separately.
The dynamics of these different variants has been reflected in their different rates of growth and prevalence over time, rather than treating them all as a single variant.
Further studies will need to examine whether different lineages and sublineages have different cycle thresholds (Ct) for detection, which could change their observed prevalence. However, the results of the study demonstrate that SARS-CoV-2 will achieve new levels of fitness by developing mutations that improve its immune escape characteristics.
“Assuming the emergence of other different variants, intermittent epidemics of similar magnitudes [as Omicron, which reached a record prevalence of 7% in England at one point] may become the “new normal”.
Boosting vaccine doses and improving current COVID-19 vaccines to provide immunity against these newer variants, as well as continued monitoring, will be essential to maintaining public health.
Journal reference:
- Eales, O., de Oliveira Martins, L., Page, AJ, et al. (2022). Dynamics of competing SARS-Cov-2 variants during the Omicron epidemic in England. Nature communications. doi:10.1038/s41467-022-32096-4.