Epidemiological analysis of the first 1000 cases of SARS‐CoV‐2 lineage BA.1 (B.1.1.529, Omicron) compared with co‐circulating Delta in Wales, UK

Abstract Background The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was first reported in Wales, UK, on 3 December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results By 14 December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20–39, and most cases were double vaccinated (65.9%) or boosted (15.7%). Age‐adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%). Conclusion Key findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared with co‐circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales.

We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales.  teams and for systematic surveillance by PHW. An admission was classified as an individual with a positive PCR result for COVID-19, sequenced as Omicron, who was admitted to hospital on or 1 day before the day of their first positive test or in the 28 days following a positive test. Likewise, admission to ICU status was based on an individual being identified in ICNET as having been admitted to ITU on or 1 day before the day of their first positive test or in the 28 days following a positive test.

Vital status was determined by linking to the Public Health Wales'
Rapid Mortality Surveillance data. This surveillance is based on clinician reported deaths in confirmed cases of COVID-19 from hospitals or care homes, where the clinician suspects COVID-19 is a causative or contributory factor in the death. We carried out confirmation of deaths against ICD10-coded death certificates from the Office of National Statistics (ONS) in order to identify additional deaths, which may have occurred outside these settings.
Descriptive analysis was undertaken in R Studio, and risk ratios (hospitalisation and symptom status adjusted for age), confidence intervals and P-values were calculated in STATA 14. Reported clinical symptoms differed between cases with confirmed Omicron and those reported by cases with confirmed Delta (Table 1) (Table 1). This is in line with recent work identifying that two vaccine doses only offer short-term protection against symptomatic Omicron infection. 9,10 It is important to note, however, that this finding is likely to be biased-the majority of the first 1000 cases of Omicron, being individuals aged 20-40 years, all would have been offered the second vaccination dose in Wales by this point in time.
Omicron cases were 2.8 times more likely to report overseas travel than Delta cases identified in the same period (95% CI: 2.1-3.8, P < 0.05). This is likely due to the targeted testing in arriving travellers as part of the initial Omicron response. However, though the response to the detection of Omicron in the United Kingdom included travel restrictions on a number of African countries, 11  individual with the earliest sample date in Wales had not travelled and had no identified links to international travel. In addition to this, of the first 1000 Omicron cases in Wales who did report overseas travel, individuals most commonly reported travel to the United Arab Emirates, Sri Lanka and Germany-none of which were on the United Kingdom's 'red list' 11  compared with co-circulating Delta cases (Table 1). This reduction in the proportion of cases reporting anosmia was also described in cases experiencing adjusted sense of smell or taste during an Omicron outbreak in Norway. 12 This evidence for a reduction in the prevalence of symptoms, particularly anosmia, may be a reason for why undetected Omicron may have been circulating in Wales.
As has been observed elsewhere, this analysis revealed that the risk of hospitalisation for the initial 1000 cases of Omicron, compared with Delta, was reduced. 9,[14][15][16]

| LIMITATIONS
It is likely that the underlying risks and exposures of Omicron cases were different to cases of Delta in the community occurring at the same time.
In addition to this, due to guidelines at the time, Omicron cases received more intensive contact tracing than Delta cases. We also thank and acknowledge the Public Health Wales Pathogen Genomics laboratory team for their considerable efforts in managing samples/logistics and carrying out the sequencing of the samples that were used in this study; without the efforts of the lab team, this work would not have been possible. We also thank and acknowledge the Public Health Wales Pathogen Genomics Bioinformatics team for their significant efforts, building underpinning pipelines and supporting the analysis and processing of data generated by sequencing, which enabled this work to be carried out.

CONFLICT OF INTEREST
None.

ETHICS STATEMENT
The study presented encompasses two elements. The first of these does not require specific ethical approval, as it focuses on public health/surveillance questions that make use of sequence data and other metadata that is already shared with the wider world as part of the activities of the COG-UK consortium (https://www.