23 Dec 2021 Episode 209 Omicron

Dear colleagues,

This will be the last episode before a Christmas break.  Unfortunately, I have a problem of access to my external disk and therefore, some of the papers I was preparing will not be included.  Hence a short episode with mainly epidemiological data from South-Africa, UK and the Netherlands and some more insight in resistance.

South-Africa

Ep 209-1:  Viana summarizes the early epidemic spread in Southern Africa.  Some interesting points:

• Molecular clock suggest a first emergence around 19 Oct 2021
• From Gauteng province spread to 7 out of 8 S-A provinces and two regions in Botswana before end of November
• Remarkably, omicron is NOT obviously a recombinant virus
• It spread in an environment where about 60 % of the population had acquired immunity by infection or vaccination → immune evasion is most important characteristic.
• Hopefully the T cell response to vaccination is less affected than Ab response.

Ep 209-2: Goga discusses the profile of Break Through Infections (after Janssens vaccine Ad26.COV2.S) during the beta, delta and omicron wave. 

• 1 914 BTI-related hospitalisations – 77 in the beta period of 90 days, 1429 in the delta period of 180 days and 408 in the Omicron (30 days) periods.
• The severity of hospitalisation (% in high or intensive care) was clearly highest in beta (23%) > delta (11%) > omicron (9%)
• However, the age distribution of BTI infections is also different, with half as much HCW of 55+ and higher proportion 18-30 yrs in omicron as compared to beta and delta waves
• From Table 2 and 3, I deduce the following age-adjusted risk of hospitalization:
  • For 18-30 yrs old:            beta = 3 %; delta = 2.9 % and omicron = 1.6 %
  • For 31-54 yrs old:            beta= 10.6 %; delta = 5.9 % and omicron = 2.3 %
  • For 55+:                              beta= 23.8 %; delta = 10.8 % and omicron = 3.3 %
• So yes, it looks like omicron BTI in South-African HCW is less severe than beta or delta

Ep 209-3: Pediatric wave during omicron: 462 out of 6287 cases hospitalized: 31 received oxygen, 7 ventilated and 4 died. Children 0-4 yrs  most affected.

These hospitalization levels amongst children are much higher than in the previous three COVID-19 waves and uncharacteristically ahead of adult COVID-19-related admissions, but the severity is not very different.  Is it due to lack (or lower) immunity in children, because less exposed to infection and not vaccinated?

Ep 209-4: Nice epidemiological description of the epidemic in South-Africa by Pearson

Ep 209-5: Wolter on disease severity, based on 161,000 COVID cases

• Very clear reduced risk of hospitalization among omicron -infected individuals (2 %) when compared to other VOC (13 %) in the same time period (Oct-Dec 2021).
• Hospitalization risk highest in children < 5 yrs and people over 60 andremarkably women > men (Table 1 p.16).  
• Once in hospital, the risk for severe disease was similar between omicron and othe VOC in this time period, but, remarkably, less than in the Delta period.

Scotland, England and Netherlands

Ep 209-6: Aziz Sheikh University of Edinburgh on 23,800 omicron cases

• 50% in 20-39 yrs group.
• 10 X higher reinfections as compared to other VOC (7.6 % vs 0.7 %)
• Only 15 hospitalization, this is 0.31 X of what could be expected
• Effectivity of booster to reduce symptomatic disease = 57 %

Ep 209-7: Technical Briefing Public Health England

• Over 56,000 infections documented
  • 132 hospitalizations: of whom 13% booster vacc; 20 % unvacc; 56 % 2 dose vacc
  • 14 died within 28 days after admission
• Severity is less than delta: only 38 % chance on admission and 62 % emergency room
• Vaccine efficacy against infection decreases 10-25 % by 10 weeks after booster
• Risk on reinfection: 9.5 % Omicron in previously infected
  • 290 between 60 to 90 after first infection
  • 69 after second infection

Ep 209-8: Egginck in Netherlands confirm a 5 fold decrease for omicron in protection by full vaccination  (2 X) or previous infection.

Additional papers

Ep 209-9:  Carreno confirming strongly reduced neut activity against omicron:

• Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529
• Neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at strongly reduced levels.
• Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated but was mostly retained in vaccinated individuals.

Ep 209-10: Schubert:

• Omicron receptor binding domain (RBD) showed a weaker binding to ACE2 compared to Beta and Delta,  → arguing that improved ACE2 binding is not a likely driver of Omicron evolution
• Reduced binding of the sera from patient, vaccinated and boost-vaccinated individuals

to the Omicron RBD→ more arguments for immune escape

Ep 209-11: Rocket:

Persistence of viable SARS-CoV-2 delta in patients treated with sotrovimab and the rapid development of spike gene mutations that confer high level resistance to sotrovimab in vitro

No significant difference in SARS-CoV-2 viral load was detected when comparing the viral loads pre- and post-sotrovimab (p=0.07508) or between cases with and without resistant mutations after sotrovimab treatment