Rapid increase in Omicron infections in England during December 2021: REACT-1 study

1Since its identification in November 2021, the Omicron variant has spread rapidly across the world, driven by its ability to cause more breakthrough infections among vaccinated individuals than other variants, likely due to genetic mutations within its viral spike protein. Furthermore, vaccine-induced protection against the Delta variant (and its sub-lineages) was already found to be waning.

2The REal-time Assessment of Community Transmission-1 (REACT-1) study has been tracking the spread of the SARS-CoV-2 virus in England approximately monthly since May 2020 as England’s first wave of infections declined. REACT-1 charted the complete replacement of Alpha by Delta from round 12 (21 May to 7 June 2021) to round 13 (24 June to 12 July 2021). With round 16 (23 November to 14 December 2021) data we document Omicron’s early spread in England.

3The SARS-CoV-2 vaccination program in England evolved quickly. In September 2021 in addition to the vaccinations offered to those 16 years of age and over, children aged 12 to 15 years were offered one dose of vaccine. By 12 December 2021, the opportunity to schedule third (booster) doses had been extended to all adults (aged 18 years and over) with heightened efforts to deliver booster doses as quickly as possible. At the same time, the rollout of the vaccination program to children aged 12 to 17 years was accelerated with second doses becoming available to 12 to 15 year-olds as well as 16 and 17 year-olds.

4Here we document the early detection of Omicron in England using the community-based REACT-1 study to avoid the biases arising in case incidence data, including those due to test-seeking behavior and limited testing capacity. We compare SARS-CoV-2 swab positivity in round 16 to previous rounds.

5In round 16 (23 November to 14 December 2021), 803,864 randomly selected individuals aged 5 years and over in England were invited to participate. Of these, 129,534 (16.1%) registered and 97,089 (12.1%) provided a self-administered throat and nasal swab with a valid RT-PCR test result, including 661 samples (12 positives) obtained from 15 to 17 December 2021 (see supplementary materials and fig. S1). A total of 1,192 positive swabs were detected yielding an overall weighted prevalence of 1.41% (1.33%, 1.51%), the third highest observed since the start of data collection in REACT-1 (from 1 May 2020) (table S1).

6A P-spline model to all REACT-1 data revealed increasing weighted prevalence during round 16 starting around 1 December 2021 (Fig. 1A). We estimated a reproduction number R = 1.09 (1.04, 1.14) for the whole of round 16 based on an exponential model for the daily weighted prevalence, assuming a gamma-distributed generation time with mean 4.6 days and standard deviation of 3.1 days. Restricting to data from December, the estimate of R was 1.19 (1.10, 1.28) (Table 1). We also found an increase in weighted prevalence in those aged 18 to 54 years with R = 1.16 (1.10, 1.23) for the whole of round 16 and R = 1.29 (1.16, 1.42) for December only (Table 1), consistent with the P-spline model (Fig. 1B).

7We found strong evidence of increasing weighted prevalence in London which had the highest weighted prevalence nationally at 1.84% (1.59%, 2.12%) compared with 1.23% (1.03%, 1.47%) in round 15 (Fig. 2A and table S2). For London, we estimated an R of 1.29 (1.19, 1.40) for the whole of round 16 and 1.43 (1.24, 1.63) during December only (Table 1).

8Region-specific daily estimates of weighted prevalence confirmed a steep increase in London from 0.80% (0.36%, 1.75%) on 26 November to 6.06% (4.06%, 9.00%) on 14 December (Fig. 2B). A slower increase was observed in daily weighted prevalence in the South East, which reached 5.75% (2.60%, 12.22%) by 15 December 2021. At the Lower-Tier Local Authority (LTLA) level, eight of the ten highest smoothed estimates of prevalence over the whole of round 16 were in London (Lambeth, Kensington and Chelsea, Hammersmith and Fulham, Southwark, Islington, Westminster, Wandsworth, Camden) with estimates among these eight LTLAs ranging from 2.15% to 1.94% while the remaining two were in South West (Cornwall, Plymouth) with estimates of 1.94% and 1.81%, respectively (Fig. 2C).

9Of the 1,192 positive swabs collected during round 16, 770 lineages were determined via viral genome sequencing with at least 50% coverage (Fig. 3, A to D, and table S3), of which 56 (7.3%) were Omicron variant and all others were Delta or Delta sub-lineages. The first swab testing positive for Omicron in REACT-1 was obtained on 3 December 2021 in London (Fig. 3B and table S4). Subsequent (N = 19) cases from 7 to 12 December 2021 were detected mainly in London and southern parts of England (Fig. 3C), and from 13 to 17 December 2021, an additional 36 Omicron infections were detected, primarily in London (Fig. 3D).

10Daily estimates of the proportion of Omicron (vs. Delta and Delta sub-lineages) rapidly increased from 6 December onwards (Fig. 3E). Smoothed estimates indicated that the proportion of Omicron infections reached over 75% by 17 December 2021. We estimate a daily increase of 61.7% (46.2%, 82.7%) in the odds of Omicron infection (vs. Delta and Delta sub-lineages), conditional on swab positivity. Assuming constant dynamics of Omicron’s (and Delta’s) transmission, we estimate 8.7 (5.4, 15.5) days for Omicron to increase from 10% to 90% of all daily infections, approximately 3.5 times faster than the estimated 31.4 (22.0, 43.9) days taken for Delta to grow from 10% to 90% against Alpha.

11Based on the 56 Omicron variants detected out of 378 positives sequenced for swabs obtained from 1 to 17 December 2021, we estimate a prevalence of swab positivity for Omicron in England of 3,700 (700, 20,900) between 1 and 6 December, 142,200 (93,200, 210,000) between 7 and 12 December, and 664,800 (518,300, 803,600) between 13 and 14 December – assuming 100% sensitivity and with a weighted prevalence of 1.32%, 1.58%, and 2.14%, respectively.

12Of the 56 participants with Omicron infection confirmed by sequencing, 54 (96.4%) were adults aged 18 to 54 years, for whom we found a steep increase in prevalence during round 16. The two other participants with Omicron infection were aged 65 to 74 years and none were children. Most of the participants testing Omicron-positive lived in London (N = 30, 53.7%), where there was the fastest increase in prevalence nationally during round 16. We found a difference in mean cycle threshold (Ct) values for the N-gene with mean 27.51 for Omicron compared to 25.62 for Delta-positive swabs (p = 0.015), but no difference in mean Ct values for E-gene (table S5).

13The highest weighted prevalence in round 16 by age was observed among 5 to 11 year-olds who in December 2021 were not eligible for vaccination. Prevalence was 4.74% (4.15%, 5.40%) which was similar to that observed in round 15 at 4.76% (4.16%, 5.44%) (Fig. 1C and table S2). Out of the 97,089 individuals included in round 16, 84,185 (86.7%) gave consent for linkage to their vaccination data. Based on the linked data, in round 16 76.6% of participants aged 12 to 17 years had received one or two vaccine doses more than 14 days prior to swabbing (fig. S2). Between rounds 15 and 16 weighted prevalence fell in this group from 5.35% (4.78%, 5.99%) to 2.31% (1.91%, 2.80%).

14Again based on the linked vaccination data, in round 16, 91.2% of participants aged 65 to 74 years had received a booster vaccine dose more than 14 days prior to swabbing as had 96.8% of those aged 75 years and over (fig. S2). Reflecting the high uptake of the booster vaccine at these ages, we observed a fall in swab positivity by 40% in those aged 65 to 74 years from 0.84% (0.72%, 0.99%) in round 15 to 0.48% (0.39%, 0.59%) in round 16, and by two-thirds in those aged 75 years and over from 0.63% (0.48%, 0.82%) to 0.21% (0.13%, 0.32%) respectively (table S2).

15Weighted prevalence in round 16 was highest in larger households including 5 people at 2.73% (2.25%, 3.32%) and 6 or more people at 2.65% (2.00%, 3.50%) compared to 0.88% (0.72%, 1.09%) in single-person households; in households with one or more children at 2.43% (2.23%, 2.65%) compared to 0.85% (0.76%, 0.95%) in households without children; in those having been in contact with a confirmed COVID-19 case at 8.00% (7.25%, 8.82%) compared to 0.81% (0.73%, 0.89%) for those without such contact, and in those reporting classic COVID-19 symptoms in the month prior to swabbing at 6.96% (6.32%, 7.67%) compared to 0.62% (0.55%, 0.70%) in those without symptoms (table S6).

16In England, the first Omicron infection was recorded on 27 November 2021 [REF] and it quickly became the dominant variant, with 76% of samples processed via TaqPath laboratories having S Gene Target Failure (SGTF, an indicator of Omicron) as of 21 December 2021. Based on these data, estimates of the regional doubling time for Omicron in England during December 2021 ranged from 1.6 to 2.5 days; London had the highest regional proportion of SGTF at 90.2%, followed by the East of England at 80.0%. At the same time, the vaccine rollout in England was accelerating both among children at ages 12 years and over and in the booster program among adults.

17Against this backdrop we observed a mixed picture in round 16, characterised by i) falling prevalence of swab positivity in children aged 12 to 17 years where high levels of vaccination had been taking place, ii) high and constant prevalence in children aged 5 to 11 years who in December 2021 were ineligible for vaccination, iii) falling prevalence among older people (65 years and over) who had largely had booster vaccinations, and iv) since around 1 December 2021, rapidly rising prevalence nationally and especially in London and the South of England, coincident with the rapid rise of Omicron.

18In our data 56 Omicron infections were detected up to 17 December 2021, as the Omicron epidemic became firmly established in England. This coincided with a rapidly rising proportion of Omicron compared to Delta infections, which reflected both the rapid growth of Omicron and the replacement of Delta by Omicron. Household transmission from an Omicron index case is reportedly approximately three times higher than that of Delta, which may help explain its transmission advantage. In addition, Omicron may have greater escape from immunity conferred by vaccination than Delta, with an estimated 20 to 40 times higher antibody titer required for neutralisation. Nonetheless, in vitro studies indicate that individuals receiving a booster dose of mRNA vaccine have increased neutralisation of the Omicron variant.

19Our and the Coronavirus Infection Survey (CIS) data in England suggest that Omicron infections in the first half of December 2021 predominated among young adults in which hospitalization rates are much lower than in older people, potentially biasing comparisons of variant severity despite attempts to correct for this statistically. Although Omicron appears less severe than Delta, a reduced risk of hospitalization could be rapidly offset by the observed exponential growth, which could then spill over into more vulnerable populations.

20We estimate that the prevalence of swab positivity in England reached over 600,000 between 13 to 17 December. Estimates from the UK Health Security Agency indicate that there were 69,147 confirmed Omicron cases and 137,148 SGTF cases in the national testing data to 21 December 2021. However, these figures are likely underestimates, since they depend on people presenting for testing, and unlike community-based studies such as REACT-1 and CIS, they do not include asymptomatic cases. Community-based surveillance studies can be critical in providing situational awareness and estimates of infection prevalence that are not biased by access to testing. Monitoring of hospitalizations data is also important. For example, during the period 12-21 December 2021, COVID-19 hospitalizations rose over 50% in London, a pattern not observed in areas with lower prevalence of Omicron.

21Our findings in children aged 12 to 17 years amongst whom the vaccination program had been accelerated are encouraging. Since round 15 (19 October to 5 November 2021) we saw prevalence in this group fall by over a half, while it remained unchanged amongst children aged 5 to 11 years who had not been vaccinated. This strongly suggests that even a single dose of vaccine was effective against infection in children aged 12 to 17 years, although this was predominantly against Delta; indeed, we did not detect any Omicron infections through sequencing of positive swabs in children, despite them having the highest prevalence of infections overall. Our findings are similarly encouraging among older people (ages 65 years and over) among whom prevalence fell substantially, although, again, these results mostly applied to Delta infections.

22Our study has limitations. Our response rate was 12.1% (i.e., returned and valid tests compared with invitations), which, despite weighted correction of our prevalence estimates, could have introduced bias into our estimates. Although all PCR-positive samples were sent for sequencing, reliable sequence data (at least 50% genome coverage) were obtained on around 60% of samples. We estimated R based on a generation time distribution estimated for Delta. To the extent that generation time may be shorter for Omicron, we may have over-estimated R during the latter part of round 16; however, our estimates of doubling time and probability that R was greater than one were unaffected. With Omicron being first observed in our data half-way through round 16, we only had two weeks of data collection in which to monitor the spread of Omicron versus Delta. The small number of sequenced Omicron cases precluded us from estimating Omicron-specific vaccine effectiveness directly.

23We have documented the rapid rise of Omicron infections in England during December 2021. We found evidence for the effectiveness of vaccination in adolescents and of booster vaccinations in older adults, although this was predominantly against Delta. Thus, further data are needed to assess how well booster vaccines protect against Omicron. Moreover, given that vaccines may take up to two weeks to have their full protective effect, vaccination alone may well be insufficient to control the spread of Omicron, at least over the short term. Additional measures beyond vaccination have been needed to prevent health services in England and other countries from being overwhelmed.