IATA Medical Contact Group - Key questions relating to Omicron

Transmissibility

The increased transmissibility is not in question. Omicron has been detected in over half of countries, and is in circulation in over 50 of them; it has become dominant in South Africa, US, UK, Denmark and Portugal. It can double in 48 hours, and it can be expected that widespread circulation will become established in most locations. A few States with such circulation have now relaxed border restrictions, recognising that these will confer no benefit in limiting spread.

The figure below shows dramatically how Omicron outcompeted Delta to become dominant in USA:



On transmission dynamics in SA - Yang and Shaman: https://doi.org/10.1101/2021.12.19.21268073
“Based on findings for Gauteng province, Omicron is estimated 100.3% (95% CI: 74.8 - 140.4%) more transmissible than the ancestral SARS-CoV-2 and 36.5% (95% CI: 20.9 - 60.1%) more transmissible than Delta; in addition, Omicron erodes 63.7% (95% CI: 52.9 - 73.9%) of the population immunity, accumulated from prior infections and vaccination, in Gauteng.”

Vaccine Performance

More studies showing reduced protection from Omicron amongst those with two doses of vaccine, but improvement with boosters – these studies looked at the Chinese vaccines sinopharm, coronavac and ZF2001 (the latter a protein sub-unit vaccine)
https://www.biorxiv.org/content/10.1101/2021.12.16.472391v1

And similarly with the Sinopharm vaccine - Yu et al:
https://www.medrxiv.org/content/10.1101/2021.12.17.21267961v2

And another study similar to others with mRNA vaccines, showing a degree of vaccine escape – Edara et al https://www.biorxiv.org/content/10.1101/2021.12.20.473557v1

Oxford found the AZ vaccine booster effective against Omicron: https://www.astrazeneca.com/media-centre/press-releases/2021/vaxzevria-significantly-boosted-antibody-levels-against-omicron.html “Neutralising antibody levels against Omicron following a third dose boost of Vaxzevria were broadly similar to levels achieved after two doses against the Delta variant”. https://www.biorxiv.org/content/10.1101/2021.12.03.471045v2.full.pdf

A WHO presentation from a week ago also provides good background on Omicron in terms of immune escape: PowerPoint-Präsentation (who.int) “In contrast to the currently circulating Delta variant, the neutralization efficiency of vaccine sera against Omicron is reduced (up to 37x) Despite the reduction, high antibody titers still allow neutralization of SARS-CoV-2 Omicron (~38-78% after 0.5m; ~25% after 3m). The higher the antibody titer (e.g. after booster vaccinations), the more likely SARS-CoV-2 Omicron might be neutralized. At low titers (2x vaccinated after 6m) there was no neutralization. Booster vaccination is therefore necessary and important…… T cell-mediated immunity could therefore represent an essential barrier to prevent severe COVID-19 upon Omicron infection.”

Severity

A new study from the University of Edinburgh in Scotland is encouraging in terms of the apparent reduced severity – and also in terms of protection from boosted vaccination. Sheikh et al: https://www.research.ed.ac.uk/en/publications/severity-of-omicron-variant-of-concern-and-vaccine-effectiveness- “These early national data suggest that Omicron is associated with a two-thirds reduction in the risk of COVID-19 hospitalisation when compared to Delta. Whilst offering the greatest protection against Delta, the third/booster dose of vaccination offers substantial additional protection against the risk of symptomatic COVID-19 for Omicron when compared to ≥25 weeks post second vaccine dose.” While it must be acknowledged that the pace of the outbreak may still severely challenge

Another study from Imperial College London also suggests reduced severity of Omicron, with around 20% reduction in hospital attendance and around 40% reduction in the likelihood of extended stay in hospital, compared with Delta infection. Ferguson et al: https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-50-severity-omicron/ The earlier Danish study had showed a less pronounced reduction.

The recent surge in Omicron cases in UK has not translated into the same number of hospitalisations as seen at this stage in previous waves. UK Omicron hospitalisations appear to be increasing at a significantly slower rate than during the Delta wave. During the Alpha wave hospitalisations were 1/17 of new cases. During the Delta wave the gap increased to a 62-fold difference. Currently, at the initial stages of the Omicron wave the new case numbers are 98x that of the 7-day lagged hospitalisations, suggesting the UK population is at 44% lower risk of hospitalisation in the current wave. (Sources: Our World in Data, Airfinity).

The South African trial showing increased breakthrough infection but apparently reduced severity – Goga et al: https://doi.org/10.1101/2021.12.21.21268171

Of course it must be recognised that with greatly increased transmissibility, there may still be a rapid surge in hospitalisations to challenge health system capacity, even with reduced severity on average, but this may be more short-lived and less overwhelming than was modelled in the worst-case scenarios.

Treatment

The antivirals, Pfizer’s PAXLOVID and Merck’s somewhat less effective molnupiravir, are expected to retain activity against Omicron because of their modes of action.

Amongst the various antibody treatments, many are not effective but sotrovimab has demonstrated retained efficacy (source: Airfinity).

Also, AstraZeneca has announced that studies show that its long acting antibody combination “EVUSHELD” which can be given prophylactically to high risk (eg immune suppressed) people, is effective against Omicron – see company release: https://www.astrazeneca.com/media-centre/press-releases/2021/evusheld-long-acting-antibody-combination-retains-neutralising-activity-against-omicron-variant-in-studies-from-oxford-and-washington-universities.html

Flight-associated transmission

Response from IATA to some rather dramatized recent headlines regarding Omicron, and flight-associated transmission, is here:
https://www.iata.org/en/pressroom/2021-releases/2021-12-22-01/

Other COVID Information

A thoughtful article by Heymann and Peeling from LSHTM on the role of testing, and the transition “from pandemic response to control” here: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02346-1/fulltext

And a RCT of early outpatient treatment with Remdesevir showed dramatic (2 cases vs 15 in control group) reduction in hospitalisation/death – Gottlieb et al: https://www.nejm.org/doi/full/10.1056/NEJMoa2116846

EU has introduced its nine-month cap on vaccination certificates – nine months no longer seems long as a period before booster administration, and Israel is now introducing a fourth (booster) dose for over-60’s, with Germany considering the same.

The Pfizer antiviral Paxlovid has received EUA in the US – but there are warnings of supply problems for many months to come.
Pfizer is also evaluating vaccination in the 6mth-5year age group.
A study showed the Moderna booster is very effective at improving antibody neutralisation.
Work is under way on an Omicron modification of the Oxford/AstraZeneca vaccine.
The European Medicines Authority and WHO have approved Novavax for emergency use.
(Sources: BlueDot, Airfinity).

CDC level changes - Upgraded to level 4 (Very High): Bonaire, Chad, Finland, Gibraltar, Lebanon, Monaco, San Marino, Spain.
Moving to level 3 (High): Peru (from level 2), Albania, St Vincent (from level 4).
Moving to level 2 (Moderate): Bahamas, Comoros, Grenada, Honduras, St Pierre & Miquelon
Moving to level 1 (from level 2): Fiji
Moving to unknown: French Guyana, Moldova, Sudan

Best wishes,
David Powell
IATA Medical Advisor