IATA Medical Contact Group COVID-19 - Omicron and vaccine escape

Omicron

Numbers of confirmed Omicron cases continue to rise dramatically but it is clear that because of low sequencing rates in many countries, actual numbers will greatly exceed those reported.  We still await clarity on the apparently (but not yet established) milder spectrum of disease with Omicron, and whether that will be outweighed, in terms of health system impacts, by the greater transmissibility.  At this early stage UK reports only 16 hospitalisations and one death from Omicron (with some thousands of cases). https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1041210/20211215_OS_Daily_Omicron_Overview.pdf

Here’s an updated technical communication from WHO on Omicron summarising the current state of knowledge:
https://www.who.int/publications/m/item/enhancing-readiness-for-omicron-(b.1.1.529)-technical-brief-and-priority-actions-for-member-states

Despite their cautions, a reasonably consistent picture seems to be emerging as to vaccine protection against Omicron, looking at several pre-print studies:

A briefing from Discovery South Africa estimated the effectiveness of 2 doses of the Pfizer vaccine against severe disease from the Omicron variant to be about 70% (Source: Airfinity) and against total infection, only about 33%.  Of course, this is based on very early data.

Andrews et al (UK): https://www.medrxiv.org/content/10.1101/2021.12.14.21267615v1.full.pdf
“Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.”

Lu et al (Hong Kong): https://www.medrxiv.org/content/10.1101/2021.12.13.21267668v1.full.pdf
Only 20-24% of [Pfizer] isolates had neutralising antibodies against Omicron, and none of the Coronavac isolates did.  “Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.”

Garcia-Beltran (USA):  https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1.full.pdf
“…neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses…”

Also Basile et al (Australia):  https://www.biorxiv.org/content/10.1101/2021.12.12.472252v1
“… four weeks after a third dose, neutralizing antibody titres are boosted. Despite this increase, neutralising antibody titres are reduced 4-fold for Omicron”

Similarly Nemet et al (Israel): https://www.medrxiv.org/content/10.1101/2021.12.13.21267670v1.full.pdf
“… low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.”

A couple more pre-print papers on immune escape/vaccine protection are here:

Zhang et al (China): https://www.tandfonline.com/doi/full/10.1080/22221751.2021.2017757 pointing to significant waning, and
Gardner & Kilpatrick (USA):  https://www.medrxiv.org/content/10.1101/2021.12.10.21267594v2 “….Omicron increased the risk of hospitalization four to five-fold and increased the risk of symptomatic disease seven to ten-fold for mRNA vaccinees, with similar relative effects for recently vaccinated, or individuals with waned antibody titers.” 

So the key questions (increased transmissibility, increased vaccine escape and possible decreased severity of illness spectrum) are only beginning to begin to yield answers, and the combination of how they will interact is far from clear.  

Note that Australia is following the lead of UK in lifting its travel restrictions from Southern Africa that were triggered by Omicron.

Information on other than Omicron:

Regarding treatment, Pfizer’s antiviral Paxlovid was found to retain the efficacy seen in the interim analysis if used within 3 days of symptom onset and efficacy increased from 85% in the interim to 87% in the full analysis if treated within 5 days.  Note also:   It is expected that both antivirals Paxlovid and Merck’s molnupiravir will retain efficacy against Omicron, because of their mechanism of action (unlike REGEN-CoV and monoclonal antibody treatments).  

According to a pre-print from Goldberg et al in Israel on vaccine effects (https://www.medrxiv.org/content/10.1101/2021.12.04.21267114v1),
“Protection from reinfection decreases with time since previous infection, but is, nevertheless, higher than that conferred by vaccination with two doses at a similar time since the last immunity-conferring event. A single vaccine dose after infection helps to restore protection.”

The Delta variant wasn’t actually associated with more severe disease according to this US review from CDC – see Kuehn: https://jamanetwork.com/journals/jama/fullarticle/2787105

As far as CDC level changes go this week – Greenland, Italy and Mauritius all upgrade from level 3 to level 4, while Malaysia does the opposite. Downgraded from level 3 to 2 are:  DRC, Jamaica, Philippines, and St Maarten. Equatorial moves from level 2 to 1, and Tanzania moves to unknown.

Best wishes,
David Powell
IATA Medical Advisor