Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021–September 2022

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections and detected Omicron subvariant emergence contemporaneous with national surveillance. SIREN methodology can be used for variant surveillance.

Since June 2020, the SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) study has conducted routine PCR testing in UK healthcare workers and sequenced PCR-positive samples. SIREN detected increases in infections and reinfections and detected Omicron subvariant emergence contemporaneous with national surveillance. SIREN methodology can be used for variant surveillance. 12 months, then had quarterly serologic testing. We confirmed vaccination status through linkage to personal identifiable information in national vaccination registries (1). This study was approved the Berkshire Research Ethics Committee (approval no. IRAS ID 284460, REC reference no. 20/SC/0230) on May 22, 2020; the vaccine amendment was approved on January 12, 2021 (study registration no. ISRCTN11041050).
SIREN samples were processed according to local protocols. Data from sites were supplied through the national laboratory reporting systems and obtained through linkage to personal identifiers. SARS-CoV-2 testing records for all participants, including symptomatic PCR testing outside SIREN's protocol, were stored in the SIREN database (1).
When RNA load was sufficient, local SIREN teams referred PCR-positive samples for sequencing (1). An additional self-swab kit for centralized PCR testing and sequencing at the national reference laboratory in London was initially mailed to participants who had a new infection and a history of SARS-CoV-2 primary infection or COVID-19 vaccination. Since spring 2021, participants with a positive PCR, irrespective of previous infection and vaccination status, were mailed an additional self-swab kit when available, which maximized the opportunity to improve sequencing yields.
We defined primary infection as a PCR-positive test from a participant without laboratory evidence of prior infection, such as a positive PCR test or antibody positivity before first vaccination (1). We defined reinfection as 2 PCR-positive tests separated by >90 days; or before a participant was vaccinated, a PCR-positive test >28 days after first SARS-CoV-2 IgG detection.
Infection rates during Omicron BA.1 and BA.2 subvariant dominance surpassed those observed in any previous wave ( Figure 1). This dominance was most apparent for reinfection rates, which exceeded primary infection rates for the first time in December 2021 and peaked at 94.2 reinfections/1,000 participants tested in January 2022 ( Figure 1). The study cohort was well characterized and highly vaccinated and had high rates of prior infections. Thus, SIREN data suggest infection-acquired and vaccine-acquired immunity were less protective against Omicron BA.1 subvariant infection.
Since May 2022, we have detected a sixth wave of SARS-CoV-2 infections in the SIREN cohort, and rates continue to increase across the United Kingdom. These findings coincide with emergence of newer Omicron BA.4 and BA.5 subvariants (8). In contrast to the first wave of Omicron BA.1 variant infections, rates of reinfections remain considerably lower than primary infections, likely because protection improved after BA.1 and BA.2 infections and vaccination.
During March 3, 2020-September 30, 2022, SIREN recorded 18,319 participant infection episodes, of which 5,261 (28.7%) had valid sequence and infection data available, comprising 4,085 primary infections and 1,1176 reinfections. Our sequence yield was comparable to other studies (8,9), but we continue to expand data linkage and sample flows to improve data completeness.
SIREN sequencing identified several SARS-CoV-2 variants (Figure 2 (8,10). We consider SIREN dates comparable with national surveillance data, which also contains sequence data from travelers and focused variant detection exercises.

Conclusions
Established early in the COVID-19 pandemic, SIREN has monitored infection trends and emerging variants for >2 years, directly informing the United Kingdom's national response (2)(3)(4), and contributing to Variant Technical Group briefings and government reports (8,11). After 4 successive variant waves with similar reinfection profiles, SIREN data showed that Omicron BA.1 and BA.2 subvariants emerged and caused a rapid rise in primary infection and reinfection rates among SIREN participants, regardless of vaccination status. Each subsequent Omicron subvariant was detected within a similar timeframe to national data (8), authenticating SIREN's use as a robust and representative surveillance tool.
The SIREN study population represents a highly exposed group who also have contact with vulnerable patients. In the absence of universal symptomatic PCR testing, SIREN provides a sustainable, focused, objective-driven sentinel surveillance platform and access to key epidemiologic variables, such as symptom severity. Although our cohort of predominantly healthy, working age, highly vaccinated adults are not representative of the general population, our study complements other national surveillance programs that target community and older populations (10,12). SIREN continues to improve its surveillance across a sentinel healthcare worker network in 135 national health organizations and support timely detection of infection trends and emerging variants, keeping pace with other surveillance tools. After a sixth wave of UK infections, concerns have grown around winter healthcare pressures combined with high rates of influenza observed in the Southern Hemisphere (13). Ongoing effective COVID-19 surveillance integrated with influenza and other respiratory pathogen surveillance is essential and achievable through SIREN's sentinel nature (7,14). SIREN will continue testing through March 31, 2023, and will continue to be a key asset in the UK surveillance strategy (7,14). The findings from SIREN can inform other countries' transitions from comprehensive surveillance to sentinel surveillance of key populations, such as healthcare workers.