Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England.

Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.

Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys.

Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage. Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022). Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4-67.2) were BA.1; N=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required. Funding: Department of Health and Social Care, England.

Interoperability of statistical models in pandemic preparedness: principles and reality.

We present interoperability as a guiding framework for statistical modelling to assist policy makers asking multiple questions using diverse datasets in the face of an evolving pandemic response. Interoperability provides an important set of principles for future pandemic preparedness, through the joint design and deployment of adaptable systems of statistical models for disease surveillance using probabilistic reasoning. We illustrate this through case studies for inferring and characterising spatial-temporal prevalence and reproduction numbers of SARS-CoV-2 infections in England.

Twin peaks: The Omicron SARS-CoV-2 BA.1 and BA.2 epidemics in England.

Rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to record-breaking incidence rates around the world. The Real-time Assessment of Community Transmission-1 (REACT-1) study has tracked SARS-CoV-2 infection in England using reverse transcription polymerase chain reaction (RT-PCR) results from self-administered throat and nose swabs from randomly selected participants aged 5 years and older approximately monthly from May 2020 to March 2022. Weighted prevalence in March 2022 was the highest recorded in REACT-1 at 6.37% (N = 109,181), with the Omicron BA.2 variant largely replacing the BA.1 variant. Prevalence was increasing overall, with the greatest increase in those aged 65 to 74 years and 75 years and older. This was associated with increased hospitalizations and deaths, but at much lower levels than in previous waves against a backdrop of high levels of vaccination.

Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study.

Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N = 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted OR of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community. Funding: Department of Health and Social Care, England.

Decision-making with uncertainty.

In emergency situations like the coronavirus pandemic, decisions must be made quickly, with only partial information. But good decisions are still possible using risk-benefit analysis. By Peter J. Diggle, Tim Gowers, Frank Kelly and Neil Lawrence.

Population antibody responses following COVID-19 vaccination in 212,102 individuals.

Population antibody surveillance helps track immune responses to COVID-19 vaccinations at scale, and identify host factors that may affect antibody production. We analyse data from 212,102 vaccinated individuals within the REACT-2 programme in England, which uses self-administered lateral flow antibody tests in sequential cross-sectional community samples; 71,923 (33.9%) received at least one dose of BNT162b2 vaccine and 139,067 (65.6%) received ChAdOx1. For both vaccines, antibody positivity peaks 4-5 weeks after first dose and then declines. At least 21 days after second dose of BNT162b2, close to 100% of respondents test positive, while for ChAdOx1, this is significantly reduced, particularly in the oldest age groups (72.7% [70.9-74.4] at ages 75 years and above). For both vaccines, antibody positivity decreases with age, and is higher in females and those with previous infection. Antibody positivity is lower in transplant recipients, obese individuals, smokers and those with specific comorbidities. These groups will benefit from additional vaccine doses.

Time varying association between deprivation, ethnicity and SARS-CoV-2 infections in England: A population-based ecological study.

BACKGROUND: Ethnically diverse and socio-economically deprived communities have been differentially affected by the COVID-19 pandemic in the UK. METHOD: Using a multilevel regression model we assessed the time-varying association between SARS-CoV-2 infections and areal level deprivation and ethnicity from 1st of June 2020 to the 19th of September 2021. We separately considered weekly test positivity rate and estimated debiased prevalence at the Lower Tier Local Authority (LTLA) level, adjusting for confounders and spatio-temporal correlation structure. FINDINGS: Comparing the least deprived and predominantly White areas with most deprived and predominantly non-White areas over the whole study period, the weekly positivity rate increases from 2·977% (95% CrI 2.913%-3.029%) to 3·347% (95% CrI 3.300%-3.402%). Similarly, prevalence increases from 0·369% (95% CrI 0.361%-0.375%) to 0·405% (95% CrI 0.399%-0.412%). Deprivation has a stronger effect until October 2020, while the effect of ethnicity becomes more pronounced at the peak of the second wave and then again in May-June 2021. In the second wave of the pandemic, LTLAs with large South Asian populations were the most affected, whereas areas with large Black populations did not show increased values for either outcome during the entire period under analysis. INTERPRETATION: Deprivation and proportion of non-White populations are both associated with an increased COVID-19 burden in terms of disease spread and monitoring, but the strength of association varies over the course of the pandemic and for different ethnic subgroups. The consistency of results across the two outcomes suggests that deprivation and ethnicity have a differential impact on disease exposure or susceptibility rather than testing access and habits. FUNDINGS: EPSRC, MRC, The Alan Turing Institute, NIH, UKHSA, DHSC.

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

The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.

SARS-CoV-2 infection and vaccine effectiveness in England (REACT-1): a series of cross-sectional random community surveys.

BACKGROUND: England has experienced a third wave of the COVID-19 epidemic since the end of May, 2021, coinciding with the rapid spread of the delta (B.1.617.2) variant, despite high levels of vaccination among adults. Vaccination rates (single dose) in England are lower among children aged 16-17 years and 12-15 years, whose vaccination in England commenced in August and September, 2021, respectively. We aimed to analyse the underlying dynamics driving patterns in SARS-CoV-2 prevalence during September, 2021, in England. METHODS: The REal-time Assessment of Community Transmission-1 (REACT-1) study, which commenced data collection in May, 2020, involves a series of random cross-sectional surveys in the general population of England aged 5 years and older. Using RT-PCR swab positivity data from 100 527 participants with valid throat and nose swabs in round 14 of REACT-1 (Sept 9-27, 2021), we estimated community-based prevalence of SARS-CoV-2 and vaccine effectiveness against infection by combining round 14 data with data from round 13 (June 24 to July 12, 2021; n=172 862). FINDINGS: During September, 2021, we estimated a mean RT-PCR positivity rate of 0·83% (95% CrI 0·76-0·89), with a reproduction number (R) overall of 1·03 (95% CrI 0·94-1·14). Among the 475 (62·2%) of 764 sequenced positive swabs, all were of the delta variant; 22 (4·63%; 95% CI 3·07-6·91) included the Tyr145His mutation in the spike protein associated with the AY.4 sublineage, and there was one Glu484Lys mutation. Age, region, key worker status, and household size jointly contributed to the risk of swab positivity. The highest weighted prevalence was observed among children aged 5-12 years, at 2·32% (95% CrI 1·96-2·73) and those aged 13-17 years, at 2·55% (2·11-3·08). The SARS-CoV-2 epidemic grew in those aged 5-11 years, with an R of 1·42 (95% CrI 1·18-1·68), but declined in those aged 18-54 years, with an R of 0·81 (0·68-0·97). At ages 18-64 years, the adjusted vaccine effectiveness against infection was 62·8% (95% CI 49·3-72·7) after two doses compared to unvaccinated people, for all vaccines combined, 44·8% (22·5-60·7) for the ChAdOx1 nCov-19 (Oxford-AstraZeneca) vaccine, and 71·3% (56·6-81·0) for the BNT162b2 (Pfizer-BioNTech) vaccine. In individuals aged 18 years and older, the weighted prevalence of swab positivity was 0·35% (95% CrI 0·31-0·40) if the second dose was administered up to 3 months before their swab but 0·55% (0·50-0·61) for those who received their second dose 3-6 months before their swab, compared to 1·76% (1·60-1·95) among unvaccinated individuals. INTERPRETATION: In September, 2021, at the start of the autumn school term in England, infections were increasing exponentially in children aged 5-17 years, at a time when vaccination rates were low in this age group. In adults, compared to those who received their second dose less than 3 months ago, the higher prevalence of swab positivity at 3-6 months following two doses of the COVID-19 vaccine suggests an increased risk of breakthrough infections during this period. The vaccination programme needs to reach children as well as unvaccinated and partially vaccinated adults to reduce SARS-CoV-2 transmission and associated disruptions to work and education. FUNDING: Department of Health and Social Care, England.

Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.

Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission­1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

Spatiotemporal analysis of the first wave of COVID-19 hospitalisations in Birmingham, UK.

OBJECTIVES: To evaluate the spatiotemporal distribution of the incidence of COVID-19 hospitalisations in Birmingham, UK during the first wave of the pandemic to support the design of public health disease control policies. DESIGN: A geospatial statistical model was estimated as part of a real-time disease surveillance system to predict local daily incidence of COVID-19. PARTICIPANTS: All hospitalisations for COVID-19 to University Hospitals Birmingham NHS Foundation Trust between 1 February 2020 and 30 September 2020. OUTCOME MEASURES: Predictions of the incidence and cumulative incidence of COVID-19 hospitalisations in local areas, its weekly change and identification of predictive covariates. RESULTS: Peak hospitalisations occurred in the first and second weeks of April 2020 with significant variation in incidence and incidence rate ratios across the city. Population age, ethnicity and socioeconomic deprivation were strong predictors of local incidence. Hospitalisations demonstrated strong day of the week effects with fewer hospitalisations (10%-20% less) at the weekend. There was low temporal correlation in unexplained variance. By day 50 at the end of the first lockdown period, the top 2.5% of small areas had experienced five times as many cases per 10 000 population as the bottom 2.5%. CONCLUSIONS: Local demographic factors were strong predictors of relative levels of incidence and can be used to target local areas for disease control measures. The real-time disease surveillance system provides a useful complement to other surveillance approaches by producing real-time, quantitative and probabilistic summaries of key outcomes at fine spatial resolution to inform disease control programmes.

Pan-African evolution of within- and between-country COVID-19 dynamics.

The coronavirus disease 2019 (COVID-19) pandemic is heterogeneous throughout Africa and threatening millions of lives. Surveillance and short-term modeling forecasts are critical to provide timely information for decisions on control strategies. We created a strategy that helps predict the country-level case occurrences based on cases within or external to a country throughout the entire African continent, parameterized by socioeconomic and geoeconomic variations and the lagged effects of social policy and meteorological history. We observed the effect of the Human Development Index, containment policies, testing capacity, specific humidity, temperature, and landlocked status of countries on the local within-country and external between-country transmission. One-week forecasts of case numbers from the model were driven by the quality of the reported data. Seeking equitable behavioral and social interventions, balanced with coordinated country-specific strategies in infection suppression, should be a continental priority to control the COVID-19 pandemic in Africa.

Resurgence of SARS-CoV-2: Detection by community viral surveillance.

Surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has mainly relied on case reporting, which is biased by health service performance, test availability, and test-seeking behaviors. We report a community-wide national representative surveillance program in England based on self-administered swab results from ~594,000 individuals tested for SARS-CoV-2, regardless of symptoms, between May and the beginning of September 2020. The epidemic declined between May and July 2020 but then increased gradually from mid-August, accelerating into early September 2020 at the start of the second wave. When compared with cases detected through routine surveillance, we report here a longer period of decline and a younger age distribution. Representative community sampling for SARS-CoV-2 can substantially improve situational awareness and feed into the public health response even at low prevalence.

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.