31 Dec 2021 Episode 213: Omicron forecast, children and vaccination

Fri, 12/31/2021 - 19:05

Dear colleagues,

This is the last episode of 2021, offering a good reason to look foreward and, as is often the case, the UK data can help us a lot. Obviously, the omicron wave will hit us after new year, but how bad will it really be for our health system?

With regard to children, some retrospect from UK and some additional insight on why children’s immune response is more effective. Importantly, also reassuring safety data on over 8 million Pfizer vaccinated US children 5-11 yrs.

Finally, two more papers on boosting, largely confirmatory on immunogenicity.

Omicron forecast for England

Ep 213-1 : Gerli medRxiv 30 Dec 2021 models the Omicron in England for the next 2 months

As can be seen in the figure, the new infections will peak medio Jan between 170,000 to 220,000 daily (which is 3-4 X the Jan 2021 peak) and the new hospital admissions a week later between 3,500 and 5,000 (previous peak on 13 Jan 2021 was 4,224).

In fact, the actual data on https://coronavirus.data.gov.uk/ show that we are now already at 189,000 new positive tests and 1,152 new admissions on a daily basis.

It is particularly worrying that new hospital admissions in children have already reached a peak that is higher than in the winter of 2020-2021!

Ep 213-2: Keeling et al also in medRxiv of 30 Dec present a much more detailed and nuanced modeling, taking into account:

a large proportion of the adult population will be boosted by the end of January (hence about 80 % protected against hospital admission)
varying the severity of omicron between 10 and 100% of delta
varying the measures taken to limit the spread

If no additional measures are taken and
- severity 10 % of delta: hospital admissions peak will be at 1,500 per day (= 1/3 of 2021 peak);
- severity 50 % of delta: peak admissions at 13,600 per day ( = 3 X 2021 peak)
- severity is 100 % of delta: peak admission at 27,000 per day (= 6 X 2021 peak).

Obviously, the sooner additional NPI measures are taken, the more impact. However, to really lower the total number of admissions, NPI should have been taken in December. If they are only implemented as of 3 January 2022, there will be no impact.

See very nice Figures 6 (p 8); 8 (p 10) and 9 (p 12).

Clearly, this forecast should be a warning for countries like Belgium and Netherlands, which are a bit “behind” with omicron. We will soon know whether the much more pronounced restrictions in NL will mitigate the “omicron wave” more than in Belgium.

(I was in Antwerp yesterday: never seen so many cars with a Dutch tax plate in 40 years!)

Children

Epidemiological data UK

Ep 213-3: Ward in Nature Medicine 20 Dec 2021 provides an overview of all pediatric admissions to a pediatric intensive care unit (PICU) and of MISC or PIMS-TS (pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2) during the first year of the pandemic in England.

Out of 12 million youngsters (0-17 yrs):

Overall:

Hospital admissions for COVID: 5830
Transfer to PICU = 251
Deaths = 8

PIMS-TS:

Diagnoses: 690 (most in hospital)
PICU: 309
Deaths < 5
Tended to be older and non-White
Remarkably: most MISC-PIMS were previously healthy: ¾ no previous admission to hospital!

PICU admissions (= 251)

More in babies < 1 year and especially < 1 month
More in boys
91 % had underlying co-morbidity (cancer/hematological disease, cardiovascular, respiratory, neurological)

Ep 213-4: Reinfection rate in children Jan 2020-July 2021 in UK (Mensah medRxiv 11 Dec 2021-

Children had a lower risk of reinfection than adults 0.34 vs 0.73 %),

were not associated with more severe disease or fatal outcomes.
strongly related to exposure due to community infection rates,
especially during the Delta variant wave.

Situation may change with omicron!?

Immunology in children

Ep 213-5: Yoshida Nature 22 Dec 2021: Comparison of local and systemic responses in children and adults:

The airway epithelium has a higher steady-state expression of IFN response in children. Role of plasmacytoid and myeloid dendritic cells in the nasal mucosa as first responders to SARS-CoV-2 infection.
Systemic T cell compartment is characterized by a more naive state in children, favoring generation of new effective responses.

In contrast, adults display a highly cytotoxic immune compartment in blood, likely because of

failure to restrict viral spreading, which may lead to widespread immune-related organ damage.

Higher TCR (T cell receptor) repertoire diversity in children versus adults. The acquisition of memory T and B cells during child- and adulthood, combined with reduced thymic output, shifts the adaptive immune system into a more memory-based compartment
in aged individuals, which makes it less probable that a high-affinity immune receptor is directly available against SARS-CoV-2 antigens.
The novel IFN-stimulated cell states in multiple blood cell lineages that are highly abundant in early disease in adults presents an added inflammatory feature of the already cytotoxic
immune compartment in adult COVID-19 patients, and possibly amplifies
any pathological effects of the systemic immune response.

Remember Ep 211-6: Dowell in Nature Immunology shows that after SARS-CoV-2 infection children have high antibody levels against common beta CoV (HKU-1 and OC43), but not alpha CoV (=cross-reactivity).

Neutralization of SARS-CoV-2 is robust and declines much slower than in adults.

Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal CoV.

Ep 213-6: Hause MMWR 31 Dec 2021 on side effects of 8.2 million Pfizer in 5-11 years old children

4,249 passive reporting via Vaccine Adverse Events Reporting System (VAERS) of which
- 97.6 % “not serious” mostly related to dosing or product preparation
- 100 cases more serious
  - 29 fever
  - 21 vomiting
  - 15 increased troponin
  - 12 seizures
  - 11 myocarditis (all recovering)
  - 2 girls died of a complicated underlying disease (not related, but still under review)
42,504 children in a more active “v-safe” program uncovered more side effects:
1. 55 % local and 35 % systemic
2. Most common: injection site pain, fatigue, and headache.
3. Fever: more after dose 2 (13%) than dose 1 (8%).
4. Child unable to perform normal activity the day after dose 1 (5%) and dose (7%).
5. 1 % was seeking medical care and of those 14 (0.02%) went to hospital: appendicitis (two), vomiting and dehydration (one), respiratory infection (one), and retropharyngeal cellulitis (one).

All in all, very reassuring data, but parents … should be advised that local and systemic reactions are expected after vaccination … and are more common after the second dose.

Public Health

Ep 213-7: Paget: Schools: still a gaping hole in the (English) covid strategy (BMJ 23 Dec 2021).

The authors complain that the lessons from the Delta wave have not really been taken. There is need for more vaccination, more CO2 measurement, clean air, rapid testing and systematic mask wearing. Is continental Europe better prepared to receive the children back in school?

Booster

Ep 213-8: Zeng medRxiv 29 Dec 2021 COVID-19 mRNA Booster Vaccines Elicit Strong Protection Against SARS-CoV-2 Omicron Variant in Patients with Cancer.

A bit misleading: what the authors show is that a booster lifts the neutralizing Ab response above the background level in people with various cancers. There is no mentioning of immune suppressive therapy and no data on vaccine efficacy….

Ep 213-9: Sabrina Tan medRxiv 30 Dec 2021: Homologous and heterologous booster

Both heterologous Ad26.COV2.S (Janssen) boosting and homologous BNT162b2 (Pfizer) boosting increased Omicron-specific humoral and cellular immune responses in individuals who were vaccinated at least 6 months previously with BNT162b2.