The Omicron variant - Updating our knowledge as the surge subsides

Since our last blog at the beginning of the Omicron wave, we have learned more about transmissibility, severity, and the effect of vaccination. Omicron has now been detected in all regions of the world, including those with more stringent exposure control and containment strategies for COVID-19. Some countries have yet to reach the peak of their Omicron wave. Others – including some Canadian provinces – are likely past their peak and have started reducing or removing COVID-related restrictions. This blog provides an update on what we know about the Omicron variant, which may be important to continuing to manage the current wave and prepare for future variants.

Moving in the shadows – the origins of Omicron

Omicron (B.1.1.529) was first designated a Variant of Concern (VOC) by Canada on November 28, 2021, based on evidence of increased transmissibility, increased risk of infection, and reduced vaccine effectiveness. Omicron does not appear to have evolved directly from any known variant, and has more than 50 mutations compared with original strain of the virus, including more than 30 on the spike protein. Omicron has multiple lineages (BA.1, BA.2, and BA.3), all of which arose during the same period. The BA.1 and BA.2 lineages share 32 common mutations, but each has 19 unique mutations. An Omicron sublineage, BA.1.1 has also emerged in Canada and elsewhere in the world.

There are three possible scenarios that may have given rise to Omicron. These include:

(1) early divergence from the original strain and parallel evolution in a population with poor surveillance and sequencing, where the variant went undetected;

(2) chronic COVID-19 infection of an immunosuppressed person over an extended period leading to evolution of the virus within a single person;

(3) zoonotic spillover infection from humans to an animal host where the virus evolved and subsequently spilled back into the human population.

Omicron may have emerged from any of these hypotheses, or a combination of them, but the divergence from the original strain may have occurred more than a year ago. Understanding the origins will be important to identifying where future variants may arise. For example, further surveillance of zoonotic reservoirs of SARS-CoV-2 in animals (e.g., mink, white-tailed deer, hamsters, etc.), could improve understanding of SARS-CoV-2 evolution.

Understanding increased transmissibility

Data from South Africa and modelling from the UK estimate Omicron to be 3.05 and 5.57 times more transmissible, respectively, than the Delta variant. Higher household secondary attack rates (SAR) have been observed for Omicron compared with Delta in the UK and Denmark and very high SAR have been observed in some settings such as gatherings, and parties, including among vaccinated people. Initial evidence indicates BA.2 may be more transmissible than BA.1, based on the growth of BA.2 in Denmark and the UK, and indications of a higher SAR than other Omicron lineages. BA.3 has not spread widely.

Many factors likely contribute to the growth advantage of Omicron. Some of these include:

• Immune escape: Omicron is better at causing breakthrough infections in vaccinated people than Delta, and can evade neutralization by prior infection or vaccine-acquired antibodies.
• Shorter transmission chain: Several studies have found that Omicron has a shorter incubation time (time between exposure and the beginning of infection) and a shorter serial interval (time between symptom onset in successive cases in a chain of transmission). Omicron is one to two days shorter than Delta for both metrics.
• Change to symptomology: Omicron appears to infect the upper respiratory tract and is less effective at infecting the lungs than previous variants. This could influence how infectious droplets and aerosols are spread. More people infected with Omicron may be asymptomatic compared with other VOC, and may unknowingly transmit the virus.
• Mutations changing ease of infection: Various Omicron mutations impact infectivity and immune escape differently. ACE2 remains the major receptor for the virus and Omicron appears to have greater binding affinity with ACE2 compared with previous variants. Other aspects of infectivity, such as efficient membrane fusion, may be reduced in some tissues. Infectivity may be more efficient where there is a higher expression of ACE2 receptors, as in the upper airway, where fewer virions may be needed to cause infection.

The main routes of SARS-CoV-2 transmission appear to be maintained for Omicron, and transmission is highest among close contacts and in settings with more risk factors (e.g., crowded, confined spaces with close interactions). Aerosol transmission has been observed in one hamster study, and was implicated in an epidemiologic investigation at a quarantine hotel. Analysis of surfaces in another quarantine hotel found that more than half of commonly touched surfaces in the room of an Omicron case were positive for the virus, a much higher contamination rate than previously reported in quarantine hotels for other VOC. One study has reported Omicron to be more persistent than previous variants on plastic surfaces (193.5 hours) and on skin (21.1 hours). These findings suggest that good ventilation, reduced crowding, masks, hand hygiene, and surface cleaning all remain important for reducing transmission of the Omicron variant.

Symptoms and disease severity

The symptomology of Omicron differs from previous variants and the original Wuhan strain. Positive Omicron cases report fewer lower respiratory tract symptoms, and more upper respiratory tract symptoms. The most prevalent symptoms vary by region, but runny nose and sore throat are common, and symptoms that were previously used to distinguish COVID-19 from other infections (e.g., loss of taste or smell), are less common. There is some indication that Omicron cases do not shed infectious virus for as long as Delta cases, and infection clears more quickly. Viral load does not appear to be higher in Omicron than Delta cases, but increased transmissibility means fewer virions may be needed to transmit the virus to others.

The severity of symptoms appears to be milder for Omicron compared with Delta as demonstrated by a relative reduction (as a percentage of total cases) in hospitalizations, ICU admissions, and deaths observed in many regions (e.g., the UK, Ontario). This trend appears to be consistent for most age groups, including younger children, based on early data. Factors including vaccination, booster doses, prior infection, and improved clinical treatment options are likely contributing to reduced severity of illness.

While Omicron is milder than Delta for both unvaccinated and vaccinated cases, it is not mild for everyone, as demonstrated by rising hospitalizations and deaths from COVID-19 following rapid rises in Omicron infections. Unvaccinated people are disproportionally represented among hospitalisations and deaths. The data on differences in severity for BA.1 and BA.2 are insufficient to draw any conclusions at this time.

The long-term effects of infection and the potential for post-acute COVID syndrome (PACS or “Long COVID”) due to Omicron are currently unknown, and follow-up may be more difficult for mild to moderate cases where no testing was conducted.

Vaccine effectiveness

Vaccine effectiveness (VE) against symptomatic infection with Omicron following 2-dose vaccination is reduced as compared with previous variants, but is improved with a third dose. This is consistent across many studies conducted globally to date. It is too soon to tell how long protection from a third dose persists. There is limited evidence on difference in VE for BA.1 versus BA.2, but data from the UK shows slightly higher (although not statistically significant) protection with BA.2.

VE against severe outcomes is much higher, and improves with a booster dose, reaching 95% in some studies. The risk of hospitalization from Omicron is lower for both vaccinated and unvaccinated people compared with Delta but vaccinated people have an even lower risk. Countries with higher vaccination coverage (e.g., > 75%) and greater uptake of booster doses are expected to experience less impact from the Omicron wave than countries with low levels of vaccination due to the impact of vaccination on reducing severe illness and death.

Immunity acquired from previous infection

Data from the UK, Denmark, South Africa, and Israel show immunity acquired from previous infection alone provides a lower level of protection against Omicron than for previous variants, and a higher rate of reinfection has been observed during the Omicron wave. Sera produced from vaccinated and boosted individuals produces higher levels of neutralizing antibodies than infection alone for all variants including Omicron. Prior infection in combination with vaccination appears to provide enhanced protection compared with prior infection alone.

Conclusions

The Omicron wave has led to record cases, increased hospitalizations, and deaths from COVID-19. This wave has demonstrated that rapid and high impact resurgence of the virus can occur, even in a highly vaccinated population. As some regions pass the peak of their Omicron wave there is uncertainty about the impact of future variants of SARS-CoV-2 on society, and how COVID-19 is managed alongside other respiratory and seasonal viruses. Public health measures may have to be reintroduced or scaled up periodically, and efforts to improve indoor air quality, such as better ventilation, remain important. While the public may be ready to put COVID-19 to rest, public health must ensure we are prepared to manage future outbreaks based on applying existing good practice, building on experience with Omicron, and continuing to follow new research.

Additional resources:

• COVID-19 data trends (Public Health Agency of Canada)
• Adjusting public health measures in the context of COVID-19 vaccination (Public Health Agency of Canada)
• Enhancing response to Omicron SARS-CoV-2 variant (World Health Organization)
• Assessment of the further spread and potential impact of the SARS-CoV-2 Omicron VOC (ECDC)

Authors

Juliette O'Keeffe, Angela Eykelbosh, and Anne-Marie Nicol are EH & KT Scientists at the NCCEH.