Impact of the Omicron variants on the Ongoing Pandemic

May 10, 2022

Introduction 

The emergence of the Omicron variant in November 2021 has led to a rapid surge of COVID-19 cases worldwide. Since then, Omicron has kept evolving into several different sublineages. Furthermore, recombinant Omicron variants have been detected in patients by coinfection with the two such sublineages, as well as with the delta variant. This alarming evolution of the Omicron variant reinforces the need for keeping preventive measures to protect the public.

Omicron Sublineages

The Omicron sublineages have evolved from a common ancestor. These include BA.1 (the first dominant variant), BA.2 (the currently dominant variant), and BA.3[1]. Detailed information on these variants can be further found here. BA.2 appears to have a growth advantage over BA.1[2]. Consequently, BA2 is overtaking BA.1 in many places. Comparison of the amino acid sequences of the spike proteins has shown that the sequences of BA.1, BA.2, and BA.3 differ from each other as considerably as delta does from alpha. In spite of these amino acid changes, serum antibody neutralization capacity obtained from a BA.1 infected human was shown to be relatively preserved against BA.2 and BA.3. In contrast, its neutralization capacity against the ancestral virus USA/WA1-2020 was sharply reduced[3]. BA.3 has been widely reported but remains fairly uncommon so far.

In addition to these variations in the virus genetics, a recombination of the viral genomes can occur when two different viruses infect the same cell, and the viral replicase falls off the RNA of one strain, then reattaches to the other strain and continues copying. In this context, the emergence of recombinant Omicron variants has also attracted our attention. Specifically, the BA.4 variant appears to be the result of a recombination between BA.1 and BA.3. Along the same line, Omicron XE is a recombinant of BA.1 and BA.2, and Deltacron has emerged as a recombination between BA.1 and delta[4]. Finally recently, the emergence of a BA.5 variant has been reported. Currently, the fitness of these variants remains uncertain. So far, only the XE variant has been detected globally.

Importantly, the spread of BA.2 has led to a significant increase in the number of COVID-19 cases. Yet it is uncertain whether this will eventually result in a new wave of COVID-19 cases. Some developed countries are offering a fourth dose of vaccination, and some places are reinforcing mask mandates. This is also affecting public health policy measures. Despite this uncertainty, the BA.2 variant is causing mild illness, similar to BA.1. Some studies suggest a better transmissibility of BA.2 compared to BA.1, but further validation by analyzing a large size of epidemiology data is needed.

Infection Patterns and Neutralizing Antibodies

BA.2 infection rates have shown different patterns globally. South Africa, where Omicron was first detected, had an unprecedentedly steep rise in daily infections, followed by a similarly steep decline. The percent of new daily infections due to BA.2 reached 100%, but neither daily infections nor hospitalizations increased as a result. Instead, daily infection rates described a somewhat choppy low plateau. A second pattern is exemplified by recent increases of COVID-19 cases in South Korea, Hong Kong, and New Zealand. Despite their control of COVID-19 cases early in the pandemic, the spread of Omicron, including the BA.2 variant, is causing dramatic increases in COVID-19 cases. A third pattern is seen in some countries in Europe. The peak during BA.1 infections formed a shoulder and then continued to a high peak amid the spread of BA.2.

Characterization of BA.2 has shown its immune evasion capacity against monoclonal antibody therapeutics. Like BA.1, it largely avoids sensitivity to many neutralizing monoclonals, but it remains sensitive to bebtelovimab[6], which targets a conserved epitope in the receptor binding domain of the spike protein. In a study of neutralizing antibody profiles in vaccinees after breakthrough infections [7], neutralization of BA.2 was greater after BA.1 breakthroughs than after delta breakthroughs. This suggests that BA.1 infections may indeed be limiting BA.2 spread and could help explain the situations in South Africa, the United States, and other countries that have not yet experienced a BA.2 surge. Analysis of neutralizing antibodies in uninfected vaccinees showed that neutralization of BA.1 and BA.2 were similar to each other, but poor in contrast with neutralization of the ancestral virus (8). However, after booster vaccination, the overall neutralizing antibody levels increased dramatically. Even though neutralization was still far stronger against the ancestral strain, high titers have been now evident against BA.1 and BA.2, suggesting the value of boosters against BA.2.

Conclusion

This ongoing evolution of the Omicron variant clearly expands the duration of the current pandemic. Its immune evasion and enhanced transmissibility have caused surges of COVID-19 cases even after vaccination and/or viral infection. However, a third dose of COVID-19 vaccine has shown to provide protection from severe disease and hospitalization, including from Omicron lineages. Furthermore, recent clinical studies with young children 5 through 11 years of age have shown the effectiveness of a third dose vaccination against Omicron. Certainly, booster vaccination remains an efficient preventive strategy to provide protection against the Omicron subvariants.

References

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  2. Mahase, E., Omicron sub-lineage BA.2 may have “substantial growth advantage,” UKHSA reports. BMJ, 2022. 376: p. o263.
  3. Zou, J., et al., Cross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2. bioRxiv, 2022: p. 2022.03.30.486409.
  4. Bolze, A., et al., Evidence for SARS-CoV-2 Delta and Omicron co-infections and recombination. medRxiv, 2022: p. 2022.03.09.22272113.
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  6. Westendorf, K., et al., LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. bioRxiv, 2022.
  7. Seaman, M.S., et al., Vaccine Breakthrough Infection with the SARS-CoV-2 Delta or Omicron (BA.1) Variant Leads to Distinct Profiles of Neutralizing Antibody Responses. medRxiv, 2022.
  8. Yu, J., et al., Neutralization of the SARS-CoV-2 Omicron BA.1 and BA.2 Variants. N Engl J Med, 2022.