16 Dec 2021 Episode 203 Omicron

Episode 203:  Omicron

Ep 203-1: Aggarwal medRxiv 15 Dec 2021 confirms 16 times drop in neutralization capacity towards omicron of serum/plasma from both (twice) vaccinated and convalescent patients, but booster increases the calculated or estimated vaccine efficacy.

The only monoclonal Ab with sufficient remaining neutralizing capacity is Sotrovimab

Ep 203-2: Edelstein in medRxiv 15 Dec on booster and hybrid immunity in cohort of 985 HCW:

• A Pfizer booster increased immunity that had waned 6 months post-priming in all age groups and in  previously infected individuals.
• The proportion of reinfected individuals in this group (before booster) was comparable to the proportion of breakthrough infection in previously uninfected individuals

→ Individuals with hybrid immunity (infection + vaccination) may also require a booster

But also:

• Pre-infection IgG levels in infected participants were similar to levels measured at the same timepoint in HCWs who remained uninfected (p>0.3).
• IgG GMC in those boosted 6-7 months after dose 2 was lower compared with those boosted 8-9 months after (1999-vs 2736, p=0.02).

→  It is difficult to determine  protective IgG levels and the optimal timing in 3 dose regimens

Ep 203-3: Comments of Max Koslov in Nature on “hybrid immunity”

Ep 203-4:   Schubert in medRxiv 15 Dec: two observations

• Omicron receptor binding domain (RBD) showed the weakest binding to ACE2, as compared to other variants, arguing that improved ACE2 binding is not a likely driver of Omicron evolution.
• Antibodies from either vaccinated or convalescent sera were significantly binding less against Omicron RBD than against the original Wuhan strain and other variants, consistent with lower neut titers.

Ep 203-5:  Nick Andrews medRxiv 14 Dec: real world data on VE against omicron

Set-up: a test-negative case-control design to estimate vaccine effectiveness (VE) against

symptomatic disease caused by the Omicron and Delta variants in England.

VE was calculated after primary immunization with two Pfizer or Astra-Zeneca doses, and at 2+ weeks following a Pfizer booster.

Result: Boost restores VE against delta and partly against omicron, to very similar extent after Pfizer or AZ as primary 2 dose vaccination. 

Ep 203-6: Doria-Rose medRxiv 15 Dec 2021: Booster in full Moderna vaccination scheme also restores in vitro neutralization titers to omicron and reduces the difference with beta and Wuhan

→ Boost may substantially reduce the risk of breakthrough infections (but not shown in real world)

Ep 203-7: Insights from South-Africa, compiled by Patrick Smits:

• Vaccination remains important to reduce severe disease: double dose of Pfizer is 70 % effective to prevent hospitalization
• The protective effect of previous infection has eroded: more reinfections.
• Early data suggest less severe disease by omicron, but this is in a high seroprevalence population, hence may reflect the still partly protection by infection or vaccination and not necessarily intrinsic to omicron.
• Children show lower test positivity than adults and low hospital admissions in absolute numbers, but in relative terms: 20 % higher risk of hospitalization as compared to D614G  

Ep 203-8: Very recent data on hospitalization in England and Denmark (high proportion of omicron).

• England: highest number of newly hospitalized children (65) on 12 Dec since start epidemic.
• Denmark: Omicron results in exactly the same proportion of hospitalizations (0.8%) as compared to other variants at the same time (22 Nov-12 Dec).

Ep 203-9: Battacharyya Challenges in assessing omicron severity

Important discussion on whether to vaccinate children (5-11 years):

Arguments contra:

• Relatively few children suffer from severe disease
• Pfizer vaccine seems to have very limited effect on reducing transmission of omicron.

What are the options?

1. Is doing nothing an option? That means that we give omicron free rein in this age group anyway… and that schools may close in Jan and Feb, or that mouth masks have to be worn further! Moreover, we do not know what omicron can do in the medium term in kids?.

2. This morning on radio 1, the SA doctors advised Europe: booster asap and children's vaccination asap. After all, they see more omicron hospitalizations in young people than with delta.

3. Waiting until we have a multivalent vaccine to vaccinate children with… that means not starting before Q3-Q4 2022, as long as there will be a childhood vaccine against omicron.

4. Vaccinate faster during the Christmas holidays…. So that after basic vaccination they may contract omicron and thereby build up a strong immunity?

5. What we need to know is what a recent vaccination with current vaccines can do against omicron… and then in young kids with a very strong immune response? To date, everything seems to indicate that a primed immune system that receives a recent boost is resistant to omicron…

So childhood vaccination may constitute an induction of good basic immunity, in a safe way, after which exposure to omicron will not cause too many problems, and at the same time will form a wall against further circulation.

(These arguments con and pro were formulated by a pediatrician and a vaccinologist respectively)

In the meantime, the Belgian High Council has approved the vaccine for children 5-11 years old.

See https://www.vrt.be/vrtnws/nl/2021/12/16/vaccinatie-kinderen/?deliveryName=DM174102

(sorry only available in Dutch).  

SOME CONCLUSIONS

1. A booster with Pfizer after either Astra-Zeneca or Pfizer restores protection against symptomatic disease in the real world by Delta (> 90 %), by Omicron (> 70 %). 

2. It is likely from in vitro data, but not yet shown in real world, that Moderna has a similar effect.

3. It remains unclear whether the pathogenicity of Omicron is intrinsically different from the previous variants:

• There is some suggestion of lower hospitalization in the general population, butthis v can be due to higher “herd immunity” as compared to the previous waves
• On the other hand: both in South-Africa and in England, there is suggestive data of relatively hospitalization of children.

4. The protection of booster against infection is weak, hence reinforcement of non-pharmacological interventions is urgently indicated, also during the holiday season.

5. Vaccination of primary school children has been approved by the Belgian High Council.  Despite the lower efficacy against Omicron versus Delta, the risk/benefit of vaccination remains positive both for children (to keep them out of hospital) and for the larger community (as an additional wall against the fifth wave).

Best wishes,

Guido