Omicron Variant: Protection By COVID-19 Booster Shots Wanes In About Ten Weeks

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New emerging preliminary data from UK shows booster shot protection against symptomatic COVID-19 caused by the Omicron variant appears to fade in about 10 weeks

he data was shared by U.K health authorities just before Christmas and was published in the official U.K. Health Security Agency’s SARS-CoV-2 Technical Briefing. 

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1043807/technical-briefing-33.pdf

Comparative demographics

Omicron cases described below are those identified by sequencing or genotyping.

A summary of case data for Omicron is published in the COVID-19: Omicron daily overview.

Table 3 shows the demographic distribution of Omicron cases with specimen dates in December, as compared to Delta. Figure 8 demonstrates this further as rates over time. Omicron was initially at increased frequency in Black ethnic group, however since mid- December the rates within specific ethnic groups have converged, reflecting more community transmission.

Omicron is particularly concentrated in 20 to 29 and 30 to 39 year old groups. Differences in trends by deprivation may at least partially reflect the fact that London and the South East, regions with lower deprivation Lower layer Super Output Areas, also those with the highest Omicron rates.

Table 3. Comparison of Delta (VOC-21APR-02) and Omicron (VOC-21NOV-01) cases by sex, age group, ethnic group and Index of Multiple Deprivation (IMD) quintile from 1 December to 18 December 2021

CharacteristicDelta, N = 116,939Omicron, N = 53,842
Sex  
Female60,571 (52%)28,265 (52%)
Male56,368 (48%)25,577 (48%)
Age group  
0-919,514 (17%)1,418 (2.6%)
10-1923,516 (20%)6,334 (12%)
20-2911,457 (9.8%)17,552 (33%)
30-3919,295 (17%)12,411 (23%)
40-4921,795 (19%)8,097 (15%)
50-5913,327 (11%)5,292 (9.8%)
60-695,220 (4.5%)1,845 (3.4%)
70-791,682 (1.4%)640 (1.2%)
80+1,133 (1.0%)253 (0.5%)
Ethnic group  
White101,631 (87%)42,230 (78%)
Asian7,802 (6.7%)4,366 (8.1%)
Black2,806 (2.4%)4,584 (8.5%)
Mixed3,427 (2.9%)1,960 (3.6%)
Other1,273 (1.1%)702 (1.3%)
IMD quintile  
1 (most deprived)16,788 (14%)7,117 (13%)
222,217 (19%)10,767 (20%)
324,761 (21%)11,171 (21%)
425,024 (21%)11,453 (21%)
5 (least deprived)28,149 (24%)13,334 (25%)

Severity

Descriptive epidemiology of severe outcomes of Omicron in England

To monitor the severe outcomes of Omicron infections, Omicron cases are linked to NHS data on presentation to emergency care and to UKHSA data on deaths following confirmed COVID- 19 test results. Hospitalisation was defined as attendance to emergency care which resulted in admission or transfer, and the Omicron specimen date was between 14 days prior to attendance and 1 day after attendance.

Using data up until 20 December 2021, a total of 132 individuals with laboratory-confirmed (sequencing, genotyping or SGTF) Omicron have been admitted or transferred from emergency departments. Of these, 54 (40.9%) admissions were in London.

The age range of admitted individuals was 0 to 98, years (median: 45.5); 74 (56.1%) were aged 40 years or more; 25.8% were aged 70 years or more. 55% of Omicron hospitalisations occurred in people whose self-reported ethnicity was White (British) and 8% among Black (African) people.

A total of 14 people have been reported to have died within 28 days of an Omicron COVID-19 diagnosis. The median time from Omicron specimen date to death was 4 days (range 1 to 10). The age of those dying ranged from 52 to 96 years.

Severity

Descriptive epidemiology of severe outcomes of Omicron in England

To monitor the severe outcomes of Omicron infections, Omicron cases are linked to NHS data on presentation to emergency care and to UKHSA data on deaths following confirmed COVID- 19 test results. Hospitalisation was defined as attendance to emergency care which resulted in admission or transfer, and the Omicron specimen date was between 14 days prior to attendance and 1 day after attendance.

Using data up until 20 December 2021, a total of 132 individuals with laboratory-confirmed (sequencing, genotyping or SGTF) Omicron have been admitted or transferred from emergency departments. Of these, 54 (40.9%) admissions were in London.

The age range of admitted individuals was 0 to 98, years (median: 45.5); 74 (56.1%) were aged 40 years or more; 25.8% were aged 70 years or more. 55% of Omicron hospitalisations occurred in people whose self-reported ethnicity was White (British) and 8% among Black (African) people.

A total of 14 people have been reported to have died within 28 days of an Omicron COVID-19 diagnosis. The median time from Omicron specimen date to death was 4 days (range 1 to 10). The age of those dying ranged from 52 to 96 years.

Table 4. Number of Omicron cases admitted or transferred to hospital at the end of presentation to emergency care by vaccination status, England. Data to 20 December 2021

Vaccination statusCount (n)Percentage (%)
Unlinked*64.5
Not vaccinated2720.5
Received one dose (1 to 20 days before specimen date)10.8
Received one dose, ≥21 days before specimen date75.3
Second dose ≥14 days before specimen date7456.1
Third dose or Booster ≥14 days before specimen date1712.9

* Individuals whose NHS numbers were unavailable to link to the National Immunisation Management System.

When interpreting Table 4 it should be understood that in a population with high vaccine coverage, the majority of cases will occur in vaccinated individuals. In comparison to the vaccination uptake in England there are higher proportions of cases in unvaccinated individuals and lower proportions who have received their third dose or booster. Vaccine effectiveness cannot be inferred from this table and vaccine effectiveness is described in section 2.4 below.

Risk of hospitalisation in England

Based on a record linkage of sequenced or genotyped, probable and possible Omicron cases and Delta cases (COVID-19 cases with sequenced or genotyped variant or based on S-gene negativity/positivity), a preliminary analysis of 114,144 Omicron cases and 461,772 Delta cases occurring between 22 November and 19 December, was undertaken to assess the risk of hospital admission and emergency care attendance among cases. This analysis excludes known cases of reinfection (individuals with a positive PCR result more than 90 days before the current test).

Stratified Cox proportional hazard regression assessed that the risk of presentation to emergency care or hospital admission with Omicron was approximately three-fifths of that for Delta (Hazard Ratio 0.62, 95% CI: 0.55 to 0.69). The risk of hospital admission alone with Omicron was approximately two-fifths of that for Delta (Hazard Ratio 0.38, 95% CI: 0.30 to 0.50). These analyses stratified on week of specimen and area of residence and further adjusted for age, exact calendar date, sex, ethnicity, local area deprivation, international travel and vaccination status.

This effect is still present when stratified by vaccination status. However, this is preliminary analysis including only 431 attendances to the emergency department and 70 hospital admissions with Omicron. These analyses also are not adjusted for undiagnosed previous COVID-19 infection, or co-morbidities of these individuals. It is not an assessment of in hospital severity, which will take further time to access. Despite adjusting for calendar week, there may

still be reporting delays for hospital events. It is important to highlight that these lower risks do not necessarily imply reduced hospital burden over the epidemic wave given the higher growth rate and immune evasion observed with Omicron.

Using a very similar data set, Imperial College, provided estimates that Omicron cases had a 15 to 25% (Hazard ratio 0.8; 95% CI 0.75-85) reduced risk of emergency department attendance (hospitalisations in their data set) and 40 to 49% (HR 0.55, 95% CI 0.51-59) reduced risk of a hospitalisation with a stay of one or more nights. Importantly, this group attempt to impute the effect of prior infection, highlighting that while 17% of the population have tested positive for COVID-19, this is likely to capture only one-third of total infections that have occurred in England.

Including the likelihood of previous infection, in addition to vaccination in their model, they have estimated the intrinsic risk difference between Delta and Omicron as between 0 to 30% and the reduced risk of hospitalisation in those previously infected estimated as 55 to 70%. Scotland, using their national data, performed a cohort study, to determine the risk of COVID-19 hospitalisation. The calculated rate of S gene negative reinfection was approximately 10 times that of previously detected S gene positive. Only 6.6% of S gene negative cases were detected in the 60-plus age group and 49.2% were detected in 20 to 39%. Using their model there were less individuals admitted to hospital than expected with 3 estimates highlighted:

  • all cases: 36% of expected (95% CI 22-56%), based on 18 admissions for S negative
  • all cases, followed for 7 days: 33% of expected (95% CI 15-65%), based on 7 admissions for S negative followed for 7 days
  • all cases, aged 20 to 59 years: 34.4% of expected (95% CI 25-70%), based on 15 admissions for S negative

However, there are a number of important caveats to this data:

  • limited circulation of S negative among the over 60s and therefore this estimate will lean to an over optimistic conclusion for this group
  • it does not include those tested in the NHS hospital laboratories which may give an underestimate for admissions and biases towards individuals who test in the community compared to those that test in hospitals
  • an incomplete assessment of undiagnosed previous infection of COVID-19 and any impact of waning of vaccine effectiveness in the over 60s who received their vaccination more than 8 to 10 weeks ago

Vaccine effectiveness

A test-negative case control design was used to estimate vaccine effectiveness against symptomatic COVID-19 with the Omicron variant compared to the Delta variant. Here, vaccination rates in PCR-positive cases are compared to vaccination rates in those who test negative.

Individuals who reported symptoms and were tested in pillar 2 (community testing) between 27 November and 17 December 2021 were included in the analysis. Those who reported recent foreign travel were excluded from the analysis due to differences in exposure risk and possible misclassification of vaccination status in this group.

Cases were defined as the Omicron variant or Delta variant based on whole genome sequencing, genotyping or S-gene target status on PCR testing. The Omicron variant has been associated with a negative S-gene target result on PCR testing with the Taqpath assay whereas with the Delta variant the S-gene target is almost always positive. A priori, we considered that

S-gene target failure would be used to define the Omicron variant when Omicron accounts for at least 80% of S-gene target failure cases. This meant that S-gene target status could be used from 27 November onwards.

Vaccine effectiveness was estimated by period after dose 2 and dose 3. The final analysis included 147,597 Delta and 68,489 Omicron cases. Vaccine effectiveness against symptomatic disease by period after dose 2 and dose 3 is shown in Figure 7 for those who received a primary course of the AstraZeneca vaccine (Figure 10A), Pfizer (Figure 10B) or Moderna (Figure 10C). Booster estimates are separated for Pfizer and Moderna boosters. In all periods, effectiveness was lower for Omicron compared to Delta.

Among those who received an AstraZeneca primary course, vaccine effectiveness was around 60% 2 to 4 weeks after either a Pfizer or Moderna booster, then dropped to 35% with a Pfizer booster and 45% with a Moderna booster by 10 weeks after the booster.

Among those who received a Pfizer primary course, vaccine effectiveness was around 70% after a Pfizer booster, dropping to 45% after 10-plus weeks and stayed around 70 to 75% after a Moderna booster up to 9 weeks after booster.

Figure 10. Vaccine effectiveness against symptomatic diseases by period after dose 1 and dose 2 for Delta (black squares) and Omicron (grey circles) for (A) recipients of 2 doses of AstraZeneca (ChAdOx1) vaccine as the primary course and (B) recipients of 2 doses of Pfizer (BNT162b2) vaccine as the primary course (C) recipients of 2 doses of Moderna (mRNA-1273) vaccine* as the primary course

Supplementary data is not available for this figure.

* Numbers were too low to estimate booster vaccine effectiveness amongst recipients of a primary course of the Moderna vaccine.

These results should be interpreted with caution due to the low counts and the possible biases related to the populations with highest exposure to Omicron (including travellers and their close contacts) which cannot fully be accounted for.

With previous variants, vaccine effectiveness against severe disease, including hospitalisation and death, has been significantly higher than effectiveness against mild disease (that is, those detected through community testing and included here). Initially to estimate effectiveness against hospitalisation the risk of symptomatic cases going on to be hospitalised in vaccinated compared to unvaccinated as assessed in a survival model can be combined with symptomatic disease effectiveness in a 2-step approach.

Although this analysis has been trialled, the number of cases admitted to hospital following testing positive in the community is too small. It will be a few weeks before effectiveness against severe disease with Omicron can be estimated, however based on experience with previous variants, this is likely to be substantially higher than the estimates against symptomatic disease. After the emergence of Delta in the UK, early estimates of vaccine effectiveness against mild infection after 2 doses of vaccine were substantially attenuated in comparison to alpha. Analysis of protection against hospitalisation however, showed no diminution of protection when comparing the 2 variants.

Reinfections

Cases of reinfection (at any interval) extracted on 19 December 2021 were identified amongst confirmed and probable Omicron variant SARS-CoV-2 positive cases with a specimen date between 1 November and 18 December 2021. Of 116,683 individuals identified with an Omicron infection in this period, 11,103 individuals (9.5%) were linked to previous confirmed infection (by PCR or LFD testing) and had an interval from the previous test positive of >=90 days. These cases would therefore have been identified as a reinfection based on the diagnosis used in ongoing surveillance (an interval between 2 sequential positive SARS-CoV-2 test results of

>=90 days).

The case ages ranged from infants to people in their 90s (median 27 years) and the interval to reinfection from previous SARS-CoV-2 infection ranged from 90 to 650 days (median 343 days) with first episodes occurring both within periods of Alpha and Delta variant dominance and earlier. There were 69 individuals for whom the Omicron infection was their third episode of infection (>=90 days between each episode). There were 290 individuals with a possible reinfection between a 60 to 89 day interval after an earlier confirmed infection but in those with an interval of <90 days between episodes it can be difficult to distinguish reinfection from persistent detection of virus.

Reinfection rates are usually generated using the population of previous infections eligible to become a reinfection (that is with a previous positive test result >=90 earlier). Using this as a measure of current reinfection rates in the population there is now a marked increase in overall reinfection rates, this is disproportionate to the increase in first infections (Figure 11). Further information on overall reinfections is published in the UKHSA National flu and COVID-19 surveillance reports (week 51).

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