Loading...
Visit our Evidence-Based Covid-19 Website and Stay Up to Date with the latest Research.
Volume:4 Issue:12 Number:3 ISSN#:2563-559X
OE Original

Omicron Updated: Key Questions Answered

Authored By: OrthoEvidence

December 22, 2021

How to Cite

OrthoEvidence. Omicron Updated: Key Questions Answered. OE Original. 2021;4(12):3. Available from: https://myorthoevidence.com/Blog/Show/163

Highlights


  • - Current limited evidence suggests that the Omicron variant has increased transmissibility over the Delta variant.


  • - A reduction in the vaccine protection against Omicron should be expected.


  • - A booster dose can increase the neutralization titers against the Omicron variant and ameliorate the reductions in vaccine protection.


  • - Being vaccinated could reduce the risk of getting severe disease caused by the Omicron variant.


  • - Prompt actions such as a quick booster campaign must be taken to contain the Omicron spread.




Evidence regarding the SARS-CoV-2 Omicron variant of concern (VOC) has been fast emerging since our last OE Original: The Rise of the Omicron SARS-CoV-2 Variant of Concern: Uncertainties Remain, But Readiness Is All. In this update, we tried to find answers from current available evidence to several key questions regarding the Omicron VOC.





Question #1:

How transmissible is Omicron?


Current limited evidence suggests that the Omicron VOC might possess an increased transmissibility over the currently dominant Delta VOC, which has been known to be more transmissible than previously dominant SARS strains such as the Alpha VOC. A previous study found that the Delta VOC was 58% to 120% more transmissible than the Alpha VOC.


To estimate the odds of household transmission for Omicron cases, compared to that for Delta cases, The United Kingdom (UK) Health Security Agency carried out a cohort analysis, involving over 110,000 cases (UK Health Security Agency, 2021). Household transmission was defined as “an index (first) case followed by one or more laboratory confirmed SARSCoV-2 cases at the same private dwelling within a 14-day period (minimum 7 days follow-up)” (UK Health Security Agency, 2021). Results showed that household transmission from an Omicron index case was 2.9 times [adjusted odds ratio (OR), 95% confidence interval (CI): 2.4 to 3.5, P < 0.001] more likely to occur than that from a Delta index case (UK Health Security Agency, 2021).





Question #2:

What do we know about vaccinated individuals getting infected by Omicron?


Studies have reported the characteristics (including vaccination status) of COVID-19 cases attributed to the Omicron variant. For instance, The United States Centers for Disease Control and Prevention (US CDC) described 43 Omicron cases (US CDC COVID-19 Response Team, 2021). About 79% (34/43) of these Omicron cases were fully vaccinated >= 14 days before symptom onset or tested positive for SARS-CoV-2 infection. Moreover, 14 Omicron cases had received a booster dose. Fatigue, cough, and runny nose or congestion were among the most commonly reported symptoms. One vaccinated patient was admitted to hospital for 2 days, and no deaths have been reported so far.


The Norwegian Institute of Public Health (NIPH) also described a COVID-19 outbreak that occurred during a Christmas party (NIPH, 2021). Eighty of the 111 party participants (70%) were confirmed to be infected with SARS-CoV-2. Most of the participants were fully vaccinated (number not specified). Among these cases, 17 were confirmed with the Omicron variant. Sequencing of additional samples was ongoing, and the NIPH assumed that most cases were attributed to the Omicron variant. Most of the 80 COVID-19 cases reported symptoms such as cough, lethargy, headache, sore throat, and fever. However, there were no hospital admissions (NIPH, 2021).




Question #3:

How effective are current COVID-19 vaccines against the Omicron variant?

Will a booster dose help?


Current available evidence we identified all came from non-peer reviewed studies (Table 1). Most of these studies focused on the neutralizing ability of sera collected from vaccinated individuals against the Omicron VOC except one study focusing on vaccine effectiveness against Omicron in the real-world.

Overall, a decline in the vaccine protection against the Omicron VOC should be expected. Andrews et al. (2021) adopted a test-negative case-control design to estimate the vaccine effectiveness against symptomatic disease due to Omicron in England. Data showed that after 2 doses of the Pfizer-BioNTech mRNA vaccine, the vaccine effectiveness against Omicron was 88.0% (95% CI: 65.9% to 95.8%) from 2 to 9 weeks after dose 2. However, the vaccine effectiveness dropped to 48.5% (95% CI: 24.3% to 65%) from 10 to 14 weeks after dose 2 and to 34% to 37% from 15 weeks after dose 2.

The evidence from studies on neutralizing ability also suggests a reduced vaccine efficacy against the Omicron VOC as all the relevant studies reported a marked reduction in neutralization titers against the Omicron VOC in sera from individuals who had been fully vaccinated with mRNA and/or viral vector-based COVID-19 vaccines.


Evidence also suggests that a booster dose is necessary as it could ameliorate the reductions and increase the neutralization titers against the Omicron VOC. For instance, Andrews et al. (2021) found that from 2 weeks after a booster dose with the Pfizer-BioNTech vaccine, the vaccine effectiveness against symptomatic infection due to Omicron increased to 71.4% (95% CI: 41.8% to 86.0%) for recipients who had received 2 doses of the AstraZeneca vaccine and 75.5% (95%CI: 56.1% to 86.3%) for recipients who had received 2 doses of the Pfizer-BioNTech vaccine.

More data on vaccine effectiveness against the Omicron VOC in the real-world is still urgently needed.



Table 1. Summary of recent evidence

Study

Highlights

Vaccine Effectiveness

Andrews et al. (2021)

1. The vaccine effectiveness after 2 doses of the Pfizer-BioNTech vaccine was 88.0% (95% CI: 65.9% to 95.8%) against Omicron at 2 to 9 weeks after dose 2. However, the vaccine effectiveness dropped to 48.5% (95% CI: 24.3% to 65%) from 10 to 14 weeks after dose 2 and to 34% to 37% from 15 weeks after dose 2.

 

2. From 2 weeks after a booster dose with the Pfizer-BioNTech vaccine, the vaccine effectiveness against Omicron increased to 71.4% (95% CI: 41.8% to 86.0%) for AstraZeneca vaccine recipients and 75.5% (95% CI: 56.1% to 86.3%) for Pfizer-BioNTech vaccine recipients.

 

3. There was no effect against Omicron from 15 weeks after receiving 2 doses of the AstraZeneca vaccine.

Neutralizing Ability

Cele et al. (2021)

The study estimated that

1. The vaccine efficacy for preventing Omicron symptomatic infection for individuals vaccinated with the Pfizer-BioNTech mRNA vaccine was 35% (95% CI: 20% to 50%).


2. The vaccine efficacy for protecting vaccinated individuals from severe disease was 77% (95% CI: 42% to 93%).

Dejnirattisai et al. (2021)

1. Neutralization titers against Omicron were significantly reduced by about 25.1-fold (Delta vs. Omicron: 1356 vs. 54) relative to the Delta VOC in people receiving 2 doses of the Pfizer-BioNTech COVID-19 mRNA vaccine, whereas the majority of samples from individuals who had received 2 doses of AstraZeneca viral vector-based vaccine were merely able to neutralize the Omicron variant (Delta vs. Omicron: 52 vs. 10).

Gardner et al. (2021)

1. Estimated vaccine effectiveness against hospitalization due to Omicron was 84.9% (95% CI: 83.0% to 86.6%) for individuals recently received the Pfizer-BioNTech vaccine, while the vaccine effectiveness against Delta was 96.3% (95% CI: 96.1% to 96.6%).

2. Estimated vaccine effectiveness against symptomatic infections suffered declines, with an increased relative risk (1-vaccine effectiveness) of 7 to 10-fold for both Pfizer-BioNTech and Moderna mRNA vaccine recipients.

3. A third booster dose significantly restored protection. The vaccine effectiveness against hospitalization due to Omicron after the booster dose with the Pfizer-BioNTech vaccine was 91.7% (95% CI: 91.0% to 92.2%).

Ikemura et al. (2021)

1. There was a 27-fold reduction in neutralizing titers against Omicron in sera from individuals who had received 2 doses of the Pfizer-BioNTech vaccine for 3 months.

Moderna

1. Initial results showed that a booster with 50 µg of Moderna mRNA COVID-19 vaccines led to an approximately 37-fold increase in neutralization titers against Omicron.

2. A booster with 100 µg of Moderna mRNA COVID-19 vaccines resulted in an approximately 83-fold increase in neutralization titers against Omicron.

3. A 100 µg booster dose of Moderna vaccine was safe and well tolerated.

Pfizer and BioNTech

1. There was an average more than 25-fold reduction in neutralization titers against Omicron, compared to wild-type SARS-CoV-2 strain, indicating that 2 doses of Pfizer-BioNTech mRNA vaccine might not be sufficient.

2. A third dose might be necessary by increasing the neutralization titers by 25-fold, compared to 2 doses against Omicron.

Schmidt et al. (2021)

1. At 1.3 months after vaccination, the median neutralization titers were only 92 (range: 25 to 327) against Omicron, compared to 7627 (2299 to 50640) against the Wuhan-hu-1 strain, in the plasmas from individuals who had received 2 doses of the Pfizer/BioNTech or Moderna mRNA vaccine. This corresponded to a mean loss of neutralization ability by 127-fold (SD: 66) for Omicron.

2. At 5 months after vaccination, the median neutralization titers were only 126 (range: 27 to 321) against Omicron, compared to 2435 (1117 to 6228) against the Wuhan-hu-1 strain, in the plasmas from individuals who had received 2 doses of the Pfizer/BioNTech or Moderna mRNA vaccine. This corresponded to a mean loss of neutralization ability by 27-fold (SD: 17) for Omicron.

3. Plasmas from recipients of Jessen viral-vector based vaccines were very poor at neutralizing the Omicron. At 1 month after vaccination, the median neutralization titers were < 25 (range: 25 to 201) against Omicron, compared to 588 (167 to 4177) against the Wuhan-hu-1 strain. At 5 months after vaccination, the median neutralization titers were 43 (range: < 25 to 368) against Omicron, compared to 982 (52 to 5597) against the Wuhan-hu-1 strain.

4. At 1 month after a 3rd booster dose with the Pfizer-BioNTech vaccine in individuals who had been vaccinated with 2 doses of either Pfizer-BioNTech or Moderna mRNA vaccines 6 months ago, the median neutralization titers were 3871 (range: 1411 to 21300) against Omicron. Compared to the neutralization titers measured at 5 months after the 2nd dose of mRNA vaccine, this corresponded to a median increase of neutralization ability by 38-fold (range: 8 to 137) for Omicron.

Wilhelm et al. (2021)

1. Six to 7 months after vaccination, there were 11.4-fold, 20-fold, and 10-fold reductions in neutralization titers against Omicron, compared to Delta, for individuals who had received 2 doses of the Pfizer-BioNTech vaccine, for individuals who had received 2 doses of the Moderna vaccine, for individuals who had received a single dose of AstraZeneca vaccine followed by a 2nd dose of the Pfizer-BioNTech vaccine, respectively.

2. Administering a 3rd dose of the Pfizer-BioNTech vaccine resulted in an increase in neutralization titers. However, compared to the titers against Delta, neutralization titers against Omicron were still reduced (37.5-fold for 2 doses of the Pfizer-BioNTech vaccine + 1 booster with the Pfizer-BioNTech vaccine, 22.7-fold for 2 doses of the Moderna vaccine + 1 booster with the Pfizer-BioNTech vaccine, and 27.1-fold for a single dose of AstraZeneca vaccine followed by 2 doses of the Pfizer-BioNTech vaccine).

95% CI: 95% confidence interval; SD: standard deviation

 



Question #4:

What should we say to vaccine refusers in the context of Omicron?


Vaccines work. Get vaccinated as soon as possible.

Although current evidence indicates a reduction in vaccine effectiveness or neutralization titers against the Omicron variant, it does not mean vaccines are no longer working. In fact, current evidence (Table 1) never suggests that vaccines are not useful in the context of Omicron. On the contrary, it shows that vaccines can still offer protection as long as we maintain a relatively high vaccine effectiveness via a booster dose.

Additionally, despite the reduction in vaccine effectiveness and neutralization titers against Omicron, evidence indicates that being vaccinated could reduce the risk of getting severe disease caused by the Omicron VOC. A study conducted by Cele et al. (2021) predicted that the COVID-19 vaccine could still offer a 77% (95% CI: 42% to 93%) protection against the severe disease attributed to the Omicron VOC. Gardner et al. (2021) estimated that the vaccine effectiveness against hospitalization due to Omicron was 84.9% (95% CI: 83.0% to 86.6%) for individuals who had recently received the Pfizer-BioNTech vaccine.




Question #5:

What is the future with Omicron? What should we do to contain it?


The World Health Organization (WHO) determines that the overall risk related to Omicron remains very high. It seems inevitable that the Omicron variant will soon become the dominant SARS-CoV-2 strain. In fact, surveillance data just released from the US CDC showed that Omicron had topped Delta and become the most common SARS-CoV-2 variant in the US. About 73.2% COVID-19 cases were due to the Omicron variant.


The Ontario Science Advisory and Modelling Consensus Tables projected that the Omicron VOC would soon become the dominant variant in Ontario, and if no prompt actions were taken, the No. of daily cases due to Omicron will soon exceed the historic max for daily case reports. One of the most critical prompt actions is an accelerated booster campaign, involving vulnerable populations, health care workers, caregivers, and their family members. Additionally, public health measures should be maintained, and public contacts should be reduced at least by 50%. Finally, make sure therapeutics are distributed to where they are needed most to deal with potential shortages as a result of increase in hospitalizations and intensive care unit (ICU) admissions due to Omicron infection (Ontario Science Advisory and Modelling Consensus Tables).


The University of Texas COVID-19 Modelling Consortium also made projections about the emergence of Omicron in the United States. It also emphasized the importance of a booster dose. The high uptake scenario (i.e., 80% of previously vaccinated individuals are boosted by March 1, 2022) would reduce reported cases, hospitalizations, and mortality by 5% (averting 1.3 million cases), 12% (averting 168000 hospitalizations), and 13% (39000 deaths), respectively, compared to the low uptake scenario (i.e., 57% of previously vaccinated individuals are boosted by March 1, 2022).


Finally, we will use a quote from the Ontario Science Advisory and Modelling Consensus Tables to conclude, “Although uncertainty persists, waiting for more information will eliminate the opportunity for action.” We must follow current available evidence and act quickly.

 







References


Andrews, N., et al. (2021). Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. medRxiv, 2021.2012.2014.21267615. doi:10.1101/2021.12.14.21267615

Cele, S., et al. (2021). SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. medRxiv, 2021.2012.2008.21267417. doi:10.1101/2021.12.08.21267417

Dejnirattisai, W., et al. (2021). Reduced neutralisation of SARS-COV-2 Omicron-B.1.1.529 variant by post-immunisation serum. medRxiv, 2021.2012.2010.21267534. doi:10.1101/2021.12.10.21267534

Gardner, B. J., et al. (2021). Estimates of reduced vaccine effectiveness against hospitalization, infection, transmission and symptomatic disease of a new SARS-CoV-2 variant, Omicron (B.1.1.529), using neutralizing antibody titers. medRxiv, 2021.2012.2010.21267594. doi:10.1101/2021.12.10.21267594

Ikemura, N., et al. (2021). SARS-CoV-2 Omicron variant escapes neutralization by vaccinated and convalescent sera and therapeutic monoclonal antibodies. medRxiv, 2021.2012.2013.21267761. doi:10.1101/2021.12.13.21267761

NIPH. (2021). Preliminary findings from study after Christmas party in Oslo. Retrieved from https://www.fhi.no/en/news/2021/preliminary-findings-from-outbreak-investigation-after-christmas-party-in-o/

Schmidt, F., et al. (2021). Plasma neutralization properties of the SARS-CoV-2 Omicron variant. medRxiv, 2021.2012.2012.21267646. doi:10.1101/2021.12.12.21267646

UK Health Security Agency. (2021). SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing 32. Retrieved from https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1042046/Technical_Briefing_32.pdf

US CDC COVID-19 Response Team. (2021). SARS-CoV-2 B.1.1.529 (Omicron) Variant — United States, December 1–8, 2021. MMWR Morb Mortal Wkly Rep, 70, 1731-1734. doi: http://dx.doi.org/10.15585/mmwr.mm7050e1

Wilhelm, A., et al. (2021). Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies. medRxiv, 2021.2012.2007.21267432. doi:10.1101/2021.12.07.


Please Login or Join to leave comments.