Omicron, the new variant discovered in South Africa on November 24th 2021 appears to compete with the Delta variant in many respects. The potential impact of this unexpected development has unnerved everyone. Here are some important observations about the risks of Omicron derived from an initial stage report.

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The record-breaking 88,376 Omicron cases in 24 hours reported in the UK compelled the Queen to take the unprecedented step of cancelling the pre-Christmas family lunch as the 'right thing to do'. Sadly and regrettably, we do not see such bold steps from leaders elsewhere who are expected to lead by example. While the State and Central agencies are struggling to contain the disease, virtually every section of the population in India continues with the "business as usual" attitude. With the average percentage of people fully vaccinated at less than 40% in ten states in India, we have no reason to celebrate.

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Growth, population distribution and immune escape of Omicron: Crucial observations

In this context, the 'Report 49 - Growth, population distribution and immune escape of Omicron in England' from the WHO Collaborating Centre for Infectious Disease Modelling, MRC Centre for Global Infectious Disease Analysis, Jameel Institute, and Imperial College London deserves careful appraisal.

This is not a peer-reviewed report. However, in the absence of a more robust study, which is unlikely to emerge in the short term, policymakers have to study this report for any follow-up action.

In the present report, the researchers estimate the growth of the Omicron variant and its immune escape characteristics based on the analysis of data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel.

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The study

Researchers analysed the data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel to estimate the growth of the Omicron variant and its immune escape characteristics. They collected the data from the UK Health Security Agency (UKHSA) and National Health Service (NHS). Besides genotype data, they used S-gene target failure (SGTF) as a proxy for Omicron infection, given the 69-70 spike deletion present in that variant. In the PCR tests, they took measures to minimise the risk of false negatives.

After collecting the SGTF and genotyping data, researchers carried out two analyses defining an Omicron case as either:

1. Having a positive result from the SGTF analysis and specimen date between 29/11/2021 and 11/12/2021 inclusive; or
2. Having a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive.

They did the analysis using the data provided by the UK UKHSA on 15th December 2021. They restricted their analysis to cases where sex, age and symptom status were known (98% and 93% of cases in the genotype and S-gene analysis respectively).

They included 196,463 people without S gene target failure (likely to be infected with another variant) and 11,329 cases with it (likely to be infected with Omicron in the SGTF analysis, as well as 122,063 Delta and 1,846 Omicron cases in the genotype analysis.

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Results (summarised from the main report)

1. The study suggests rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (2.0-day doubling time) over the study period from both SGTF and genotype data.
2. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta.
3. Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta.
4. To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection, researchers used appropriate statistical methods to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting their analysis to symptomatic cases and matching by day, region, 10-year age band, sex and ethnicity.
5. They found a significantly increased risk of an Omicron case compared to Delta for those with vaccine status: AZ 2+weeks post-dose 2 (PD2), Pfizer 2+w PD2, AZ 2+w post-dose 3 (PD3) and PF 2+w PD3 vaccine states with hazard ratios of 1.86, 2.68, 4.32 and 4.07 respectively, where PD3 states are categorised by the dose 1/2 vaccine used.
6. Depending on the Delta VE estimates used, these estimates translate into Omicron VE estimates of between 0% and 20% PD2 and between 55% and 80% PD3 against Omicron, consistent with other estimates.
7. They obtained similar estimates using genotype data, albeit with greater uncertainty. To assess the impact of Omicron on re-infection rates they relied on genotype data since SGTF is associated with a higher observed rate of re-infection, likely due to re-infections typically having higher Ct values than primary infections and therefore being subject to a higher rate of random PCR target failure.
8. Controlling for vaccine status, age, sex, ethnicity, asymptomatic status, and region and specimen date and using suitable statistical methods to predict re-infection status, the researchers found that Omicron was associated with a 5.41 fold higher risk of re-infection compared with Delta. This suggests relatively low remaining levels of immunity from prior infection.

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Expert comments

According to Prof Deborah Dunn-Walters, Chair of the British Society for Immunology COVID-19 Taskforce and Professor of Immunology at the University of Surrey, the message from the study is clear- Do not think that if you have caught COVID before, you cannot fall ill with it again. She noted that this preprint backs up previous studies that indicate re-infections are much more common with the Omicron variant as it appears to be able to more easily evade any prior immunity gained.

Prof Deborah Dunn-Walters clarified:

“Vaccination provides you with a safe and effective way to boost your immunity levels to COVID-19, and in particular to the Omicron variant, without falling ill with the disease. This booster dose is particularly vital to get now as this research shows that three doses provide much better protection against Omicron than two vaccine doses."

"With high levels of coronavirus now circulating in our communities, it is important that everyone get their booster dose as soon as possible to maximise the level of protection they have against COVID-19. However, we also need to remember that the immune response takes time to build after receiving the booster dose. Therefore, a cautious approach to the number of people that you come into contact with is needed to make sure we all play our part in minimising the spread of COVID-19...”

Professor Penny Ward, Independent Pharmaceutical Physician, and Visiting Professor in Pharmaceutical Medicine at King’s College London noted that this second report from Imperial College uses real-world data on infection with Delta versus Omicron variants to assess the level of protection afforded by vaccines versus infection and illness with the Omicron variant compared to that caused by the Delta variant.

She cautioned:

"It is notable that the majority of confirmed Omicron infections reported in the dataset are from young adults, many of African descent, primarily in the London region, which is a pattern very different to that observed with Delta variant infections. In particular, the current clustering of cases of Omicron infection in younger age adults, who are inherently less likely to be hospitalised or to die from COVID, limits the extent to which differences in severity of illness following the infection caused by these two variants can be assessed."

“Protection conferred by vaccine boosters against infection ranged from 55-80%, dependent on the vaccine effectiveness estimates for Delta variant infection incorporated into the analysis. Notwithstanding the uncertainties in the information set caused by the uneven distribution of the variant currently, the rapid doubling time combined with reduced vaccine protection suggest, as the authors state, that 'Omicron poses an immediate and substantial threat to public health in England and more widely’," she added.

She emphasised the fact that in the absence of significant quantities of antiviral medications to use as an adjunct to vaccination across the completely high-risk population only reducing social contact decreases the potential for infecting those at greatest risk. She believes that the public has already started to do this.

"... let us hope their actions are successful and that this wave, which has risen very sharply in recent days, starts to decline quickly as Professor Whitty suggests it may.” She was referring to the views expressed by Dr. Chris Whitty, Chief Medical Officer for England, while giving evidence to the Health and Social Care Committee on the latest findings of the new Omicron variant, including transmissibility, the severity of illness, and vaccine effectiveness.

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Lessons for India

Omicron is slowly and steadily increasing its numbers nationwide. In view of its speed of transmission and other potential attributes, policymakers have to be alert. They cannot afford the new virus to overwhelm the health delivery system.

According to Professor Neil Ferguson, the lead researcher, the study provides further evidence of the very substantial extent to which Omicron can evade prior immunity given by both infection or vaccination. "This level of immune evasion means that Omicron poses a major, imminent threat to public health.” he asserted.

Prof Azra Ghani from Imperial College London another researcher in the group added:

“Quantifying re-infection risk and vaccine effectiveness against Omicron is essential for modelling the likely future trajectory of the Omicron wave and the potential impact of vaccination and other public health interventions.”

If the behaviour of the virus is country-specific, we may have to develop country-specific data to vanquish the virus. Every passing day raises uncomfortable questions. However, the most effective and universal way to overwhelm the virus is by everyone strictly complying with COVID appropriate norms.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A Ph. D. from the University of Leeds, UK, he is a medical physicist with specialisation in radiation safety and regulatory matters. He was a Research Associate at the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees.