Optimal vaccine allocation for COVID-19 in the Netherlands: a data-driven prioritization

For the control of COVID-19, vaccination programmes provide a long-term solution. The amount of available vaccines is often limited, and thus it is crucial to determine the allocation strategy. While mathematical modelling approaches have been used to find an optimal distribution of vaccines, there is an excessively large number of possible schemes to be simulated. Here, we propose an algorithm to find a near-optimal allocation scheme given an intervention objective such as minimization of new infections, hospitalizations, or deaths, where multiple vaccines are available. The proposed principle for allocating vaccines is to target subgroups with the largest reduction in the outcome of interest, such as new infections, due to vaccination that fully immunizes a single individual. We express the expected impact of vaccinating each subgroup in terms of the observed incidence of infection and force of infection. The proposed approach is firstly evaluated with a simulated epidemic and then applied to the epidemiological data on COVID-19 in the Netherlands. Our results reveal how the optimal allocation depends on the objective of infection control. In the case of COVID-19, if we wish to minimize deaths, the optimal allocation strategy is not efficient for minimizing other outcomes, such as infections. In simulated epidemics, an allocation strategy optimized for an outcome outperforms other strategies such as the allocation from young to old, from old to young, and at random. Our simulations clarify that the current policy in the Netherlands (i.e., allocation from old to young) was concordant with the allocation scheme that minimizes deaths. The proposed method provides an optimal allocation scheme, given routine surveillance data that reflect ongoing transmissions. The principle of allocation is useful for providing plausible simulation scenarios for complex models, which give a more robust basis to determine intervention strategies. Author summaryVaccination is the key to controlling the ongoing COVID-19 pandemic. In the early stages of an epidemic, there is shortage of vaccine stocks. Here, we propose an algorithm that computes an optimal vaccine distribution among groups for each intervention objective (e.g., minimizing new infections, hospitalizations, or deaths). Unlike existing approaches that use detailed information on at-risk contacts between and among groups, the proposed algorithm requires only routine surveillance data on the number of cases. This method is applicable even when multiple vaccines are available. Simulation results show that the allocation scheme optimized by our algorithm performed the best compared with other strategies such as allocating vaccines at random and in the order of age. Our results also reveal that an allocation scheme optimized for one specific objective is not necessarily efficient for another, indicating the importance of the decision-making at the early phase of distributions.

Prior infections and effectiveness of SARS-CoV-2 vaccine in test-negative study: A systematic review and meta-analysis

BackgroundPrior infection with SARS-CoV-2 can provide protection against infection and severe COVID-19. In settings with high pre-existing immunity, vaccine effectiveness (VE) should decrease with higher levels of immunity among unvaccinated individuals. Here, we conducted a systematic review and meta-analysis to understand the influence of prior infection on VE. MethodsWe included test-negative design (TND) studies that examined VE against infection or severe disease (hospitalization, ICU admission, or death) for primary vaccination series. To determine the impact of prior infections on VE estimates, we compared studies that excluded or included people with prior COVID-19 infection. We also compared VE estimates by the cumulative incidence of cases before the start of and incidence rates during each study in the study locations, as further measures of prior infections in the community. FindingsWe identified 67 studies that met inclusion criteria. Pooled VE among studies that included people with prior COVID-19 infection was lower against infection (pooled VE: 77%; 95% confidence interval (CI): 72%, 81%) and severe disease (pooled VE: 86%; 95% CI: 83%, 89%), compared with studies that excluded people with prior COVID-19 infection (pooled VE against infection: 87%; 95% CI: 85%, 89%; pooled VE against severe disease: 93%; 95% CI: 91%, 95%). There was a negative correlation between the cumulative incidence of cases before the start of the study and VE estimates against infection (spearman correlation ({rho}) = -0.32; 95% CI: -0.45, -0.18) and severe disease ({rho} = -0.49; 95% CI: -0.64, -0.30). There was also a negative correlation between the incidence rates of cases during the study period and VE estimates against infection ({rho} = - 0.48; 95% CI: -0.59, -0.34) and severe disease ({rho} = -0.42; 95% CI: -0.58, -0.23). InterpretationBased on a review of published VE estimates we found clear empirical evidence that higher levels of pre-existing immunity in a population were associated with lower VE estimates. Excluding previously infected individuals from VE studies may result in higher VE estimates with limited generalisability to the wider population. Prior infections should be treated as confounder and effect modificatory when the policies were targeted to whole population or stratified by infection history, respectively.

Antibody prevalence for SARS-CoV-2 in England following first peak of the pandemic: REACT2 study in 100,000 adults

BackgroundEngland, UK has experienced a large outbreak of SARS-CoV-2 infection. As in USA and elsewhere, disadvantaged communities have been disproportionately affected. MethodsNational REal-time Assessment of Community Transmission-2 (REACT-2) prevalence study using a self-administered lateral flow immunoassay (LFIA) test for IgG among a random population sample of 100,000 adults over 18 years in England, 20 June to 13 July 2020. ResultsData were available for 109,076 participants, yielding 5,544 IgG positive results; adjusted (for test performance) and re-weighted (for sampling) prevalence was 6.0% (95% Cl: 5.8, 6.1). Highest prevalence was in London (13.0% [12.3, 13.6]), among people of Black or Asian (mainly South Asian) ethnicity (17.3% [15.8, 19.1] and 11.9% [11.0, 12.8] respectively) and those aged 18-24 years (7.9% [7.3, 8.5]). Adjusted odds ratio for care home workers with client-facing roles was 3.1 (2.5, 3.8) compared with non-essential workers. One third (32.2%, [31.0-33.4]) of antibody positive individuals reported no symptoms. Among symptomatic cases, most (78.8%) reported symptoms during the peak of the epidemic in England in March (31.3%) and April (47.5%) 2020. We estimate that 3.36 million (3.21, 3.51) people have been infected with SARS-CoV-2 in England to end June 2020, with an overall infection fatality ratio (IFR) of 0.90% (0.86, 0.94); age-specific IFR was similar among people of different ethnicities. ConclusionThe SARS-CoV-2 pandemic in England disproportionately affected ethnic minority groups and health and care home workers. The higher risk of infection in minority ethnic groups may explain their increased risk of hospitalisation and mortality from COVID-19.

Transient dynamics of SARS-CoV-2 as England exited national lockdown

Control of the COVID-19 pandemic requires a detailed understanding of prevalence of SARS-CoV-2 virus in the population. Case-based surveillance is necessarily biased towards symptomatic individuals and sensitive to varying patterns of reporting in space and time. The real-time assessment of community transmission antigen study (REACT-1) is designed to overcome these limitations by obtaining prevalence data based on a nose and throat swab RT-PCR test among a representative community-based sample in England, including asymptomatic individuals. Here, we describe results comparing rounds 1 and 2 carried out during May and mid June / early July 2020 respectively across 315 lower tier local authority areas. In round 1 we found 159 positive samples from 120,620 tested swabs while round 2 there were 123 positive samples from 159,199 tested swabs, indicating a downwards trend in prevalence from 0.13% (95% CI, 0.11%, 0.15%) to 0.077% (0.065%, 0.092%), a halving time of 38 (28, 58) days, and an R of 0.89 (0.86, 0.93). The proportion of swab-positive participants who were asymptomatic at the time of sampling increased from 69% (61%, 76%) in round 1 to 81% (73%, 87%) in round 2. Although health care and care home workers were infected far more frequently than other workers in round 1, the odds were markedly reduced in round 2. Age patterns of infection changed between rounds, with a reduction by a factor of five in prevalence in 18 to 24 year olds. Our data were suggestive of increased risk of infection in Black and Asian (mainly South Asian) ethnicities. Using regional and detailed case location data, we detected increased infection intensity in and near London. Under multiple sensitivity analyses, our results were robust to the possibility of false positives. At the end of the initial lockdown in England, we found continued decline in prevalence and a shift in the pattern of infection by age and occupation. Community-based sampling, including asymptomatic individuals, is necessary to fully understand the nature of ongoing transmission.

Community prevalence of SARS-CoV-2 virus in England during May 2020: REACT study

BackgroundEngland has experienced one of the highest rates of confirmed COVID-19 mortality in the world. SARS-CoV-2 virus has circulated in hospitals, care homes and the community since January 2020. Our current epidemiological knowledge is largely informed by clinical cases with far less understanding of community transmission. MethodsThe REal-time Assessment of Community Transmission (REACT) study is a nationally representative prevalence survey of SARS-CoV-2 virus swab-positivity in the community in England. We recruited participants regardless of symptom status. ResultsWe found 159 positives from 120,610 swabs giving an average prevalence of 0.13% (95% CI: 0.11%,0.15%) from 1st May to 1st June 2020. We showed decreasing prevalence with a halving time of 8.6 (6.2, 13.6) days, implying an overall reproduction number R of 0.57 (0.45, 0.72). Adults aged 18 to 24 yrs had the highest swab-positivity rates, while those >64 yrs had the lowest. Of the 126 participants who tested positive with known symptom status in the week prior to their swab, 39 reported symptoms while 87 did not, giving an estimate that 69% (61%,76%) of people were symptom-free for the 7 days prior testing positive in our community sample. Symptoms strongly associated with swab-positivity were: nausea and/or vomiting, diarrhoea, blocked nose, loss of smell, loss of taste, headache, chills and severe fatigue. Recent contact with a known COVID-19 case was associated with odds of 24 (16, 38) for swab-positivity. Compared with non-key workers, odds of swab-positivity were 7.7 (2.4, 25) among care home (long-term care facilities) workers and 5.2 (2.9, 9.3) among health care workers. However, some of the excess risk associated with key worker status was explained by recent contact with COVID-19 cases. We found no strong evidence for geographical variability in positive swab results. ConclusionOur results provide a reliable baseline against which the impact of subsequent relaxation of lockdown can be assessed to inform future public health efforts to control transmission.

Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021

BackgroundFollowing rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards. AimWe characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence. MethodsOn average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions. ResultsFollowing an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was masked by the effects of vaccination and the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups. ConclusionHigh-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was highly effective at reducing risk of infection with school holidays/closures playing a significant part.

The impact of vaccinating adolescents and children on COVID-19 disease outcomes

IntroductionDespite the high COVID-19 vaccination coverage among adults, there is concern over a peak in SARS-CoV-2 infections in the coming months. To help ensure that healthcare systems are not overwhelmed in the event of a new wave of SARS-CoV-2 infections, many countries have extended vaccination to adolescents (those aged 12-17 years) and may consider further extending to children aged 5-11 years. However, there is considerable debate about whether or not to vaccinate healthy adolescents and children against SARS-CoV-2 because, while vaccination of children and adolescents may limit transmission from these groups to other, more vulnerable groups, adolescents and children themselves have limited risk of severe disease if infected and may experience adverse events from vaccination. To quantify the benefits of extending COVID-19 vaccination beyond adults we compare daily cases, hospital admissions, and intensive care (IC) admissions for vaccination in adults only, those 12 years and above, and those 5 years and above. Methods and FindingsWe developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model to simulate disease outcomes (e.g., cases, hospital admissions, IC admissions) under different vaccination scenarios. The model is partitioned into 10-year age bands (0-9, 10-19, ..., 70-79, 80+) and accounts for differences in susceptibility and infectiousness by age group, seasonality in transmission rate, modes of vaccine protection (e.g., infection, transmission), and vaccine characteristics (e.g., vaccine effectiveness). Model parameters are estimated by fitting the model piecewise to daily cases from the Dutch notification database Osiris from 01 January 2020 to 22 June 2021. Forward simulations are performed from 22 June 2021 to 31 March 2022. We performed sensitivity analyses in which vaccine-induced immunity waned. We found that upon relaxation of all non-pharmaceutical control measures a large wave occurred regardless of vaccination strategy. We found overall reductions of 5.7% (4.4%, 6.9%) of cases, 2.0% (0.7%, 3.2%) of hospital admissions, and 1.7% (0.6%, 2.8%) of IC admissions when those 12 years and above were vaccinated compared to vaccinating only adults. When those 5 years and above were vaccinated we observed reductions of 8.7% (7.5%, 9.9%) of cases, 3.2% (2.0%, 4.5%) of hospital admissions, and 2.4% (1.2%, 3.5%) of IC admissions compared to vaccination in adults only. Benefits of extending vaccination were larger within the age groups included in the vaccination program extension than in other age groups. The benefits of vaccinating adolescents and children were smaller if vaccine protection against infection, hospitalization, and transmission (once infected) wanes. DiscussionOur results highlight the benefits of extending COVID-19 vaccination programs beyond adults to reduce infections and severe outcomes in adolescents and children and in the wider population. A reduction of infections in school-aged children/adolescents may have the added benefit of reducing the need for school closures during a new wave. Additional control measures may be required in future to prevent a large wave despite vaccination program extensions. While the results presented here are based on population characteristics and the COVID-19 vaccination program in The Netherlands, they may provide valuable insights for other countries who are considering COVID-19 vaccination program extensions.

REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021

BackgroundDespite high levels of vaccination in the adult population, cases of COVID-19 have risen exponentially in England since the start of May 2021 driven by the Delta variant. However, with far fewer hospitalisations and deaths per case during the recent growth in cases compared with 2020, it is intended that all remaining social distancing legislation in England will be removed from 19 July 2021. MethodsWe report interim results from round 13 of the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a cross-sectional sample of the population of England was asked to provide a throat and nose swab for RT-PCR and to answer a questionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July 2021. ResultsIn round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalence of 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12 at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalence with an average doubling time of 15 (13, 17) days between round 12 and round 13. However, during the recent period of round 13 interim only, we observed a shorter doubling time of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There were substantial increases in all age groups under the age of 75 years, and especially at younger ages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to 24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with the largest increase in London where prevalence increased more than eight-fold from 0.13% (0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall, prevalence was over 3 times higher in the unvaccinated compared with those reporting two doses of vaccine in both round 12 and round 13 interim, although there was a similar proportional increase in prevalence in vaccinated and unvaccinated individuals between the two rounds. DiscussionWe are entering a critical period with a number of important competing processes: continued vaccination rollout to the whole adult population in England, increased natural immunity through infection, reduced social mixing of children during school holidays, increased proportion of mixing occurring outdoors during summer, the intended full opening of hospitality and entertainment and cessation of mandated social distancing and mask wearing. Surveillance programmes are essential during this next phase of the epidemic to provide clear evidence to the government and the public on the levels and trends in prevalence of infections and their relationship to vaccine coverage, hospitalisations, deaths and Long COVID.

REACT-1 round 10 report: Level prevalence of SARS-CoV-2 swab-positivity in England during third national lockdown in March 2021

BackgroundIn England, hospitalisations and deaths due to SARS-CoV-2 have been falling consistently since January 2021 during the third national lockdown of the COVID-19 pandemic. The first significant relaxation of that lockdown occurred on 8 March when schools reopened. MethodsThe REal-time Assessment of Community Transmission-1 (REACT-1) study augments routine surveillance data for England by measuring swab-positivity for SARS-CoV-2 in the community. The current round, round 10, collected swabs from 11 to 30 March 2021 and is compared here to round 9, in which swabs were collected from 4 to 23 February 2021. ResultsDuring round 10, we estimated an R number of 1.00 (95% confidence interval 0.81, 1.21). Between rounds 9 and 10 we estimated national prevalence has dropped by [~]60% from 0.49% (0.44%, 0.55%) in February to 0.20% (0.17%, 0.23%) in March. There were substantial falls in weighted regional prevalence: in South East from 0.36% (0.29%, 0.44%) in round 9 to 0.07% (0.04%, 0.12%) in round 10; London from 0.60% (0.48%, 0.76%) to 0.16% (0.10%, 0.26%); East of England from 0.47% (0.36%, 0.60%) to 0.15% (0.10%, 0.24%); East Midlands from 0.59% (0.45%, 0.77%) to 0.19% (0.13%, 0.28%); and North West from 0.69% (0.54%, 0.88%) to 0.31% (0.21%, 0.45%). Areas of apparent higher prevalence remain in parts of the North West, and Yorkshire and The Humber. The highest prevalence in March was found among school-aged children 5 to 12 years at 0.41% (0.27%, 0.62%), compared with the lowest in those aged 65 to 74 and 75 and over at 0.09% (0.05%, 0.16%). The close approximation between prevalence of infections and deaths (suitably lagged) is diverging, suggesting that infections may have resulted in fewer hospitalisations and deaths since the start of widespread vaccination. ConclusionWe report a sharp decline in prevalence of infections between February and March 2021. We did not observe an increase in the prevalence of SARS-CoV-2 following the reopening of schools in England, although the decline of prevalence appears to have stopped. Future rounds of REACT-1 will be able to measure the rate of growth or decline from this current plateau and hence help assess the effectiveness of the vaccination roll-out on transmission of the virus as well as the potential size of any third wave during the ensuing months.

REACT-1 round 9 final report: Continued but slowing decline of prevalence of SARS-CoV-2 during national lockdown in England in February 2021

BackgroundEngland will start to exit its third national lockdown in response to the COVID-19 pandemic on 8th March 2021, with safe effective vaccines being rolled out rapidly against a background of emerging transmissible and immunologically novel variants of SARS-CoV-2. A subsequent increase in community prevalence of infection could delay further relaxation of lockdown if vaccine uptake and efficacy are not sufficiently high to prevent increased pressure on healthcare services. MethodsThe PCR self-swab arm of the REal-time Assessment of Community Transmission Study (REACT-1) estimates community prevalence of SARS-CoV-2 infection in England based on random cross-sections of the population ages five and over. Here, we present results from the complete round 9 of REACT-1 comprising round 9a in which swabs were collected from 4th to 12th February 2021 and round 9b from 13th to 23rd February 2021. We also compare the results of REACT-1 round 9 to round 8, in which swabs were collected mainly from 6th January to 22nd January 2021. ResultsOut of 165,456 results for round 9 overall, 689 were positive. Overall weighted prevalence of infection in the community in England was 0.49% (0.44%, 0.55%), representing a fall of over two thirds from round 8. However the rate of decline of the epidemic has slowed from 15 (13, 17) days, estimated for the period from the end of round 8 to the start of round 9, to 31 days estimated using data from round 9 alone (lower confidence limit 17 days). When comparing round 9a to 9b there were apparent falls in four regions, no apparent change in one region and apparent rises in four regions, including London where there was a suggestion of sub-regional heterogeneity in growth and decline. Smoothed prevalence maps suggest large contiguous areas of growth and decline that do not align with administrative regions. Prevalence fell by 50% or more across all age groups in round 9 compared to round 8, with prevalence (round 9) ranging from 0.21% in those aged 65 and over to 0.71% in those aged 13 to 17 years. Round 9 prevalence was highest among Pakistani participants at 2.1% compared to white participants at 0.45% and Black participants at 0.83%. There were higher adjusted odds of infection for healthcare and care home workers, for those working in public transport and those working in education, school, nursery or childcare and lower adjusted odds for those not required to work outside the home. ConclusionsCommunity prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.

REACT-1 round 9 interim report: downward trend of SARS-CoV-2 in England inFebruary 2021 but still at high prevalence

Background and MethodsEngland entered its third national lockdown of the COVID-19 pandemic on 6th January 2021 with the aim of reducing the daily number of deaths and pressure on healthcare services. The real-time assessment of community transmission study (REACT-1) obtains throat and nose swabs from randomly selected people in England in order to describe patterns of SARS-CoV-2 prevalence. Here, we report data from round 9a of REACT-1 for swabs collected between 4th and 13th February 2021. ResultsOut of 85,473 tested-swabs, 378 were positive. Overall weighted prevalence of infection in the community in England was 0.51%, a fall of more than two thirds since our last report (round 8) in January 2021 when 1.57% of people tested positive. We estimate a halving time of 14.6 days and a reproduction number R of 0.72, based on the difference in prevalence between the end of round 8 and the beginning of round 9. Although prevalence fell in all nine regions of England over the same period, there was greater uncertainty in the trend for North West, North East, and Yorkshire and The Humber. Prevalence fell substantially across all age groups with highest prevalence among 18- to 24-year olds at 0.89% (0.47%, 1.67%) and those aged 5 to12 years at 0.86% (0.60%, 1.24%). Large household size, living in a deprived neighbourhood, and Asian ethnicity were all associated with increased prevalence. Healthcare and care home workers were more likely to test positive compared to other workers. ConclusionsThere is a strong decline in prevalence of SARS-CoV-2 in England among the general population five to six weeks into lockdown, but prevalence remains high: at levels similar to those observed in late September 2020. Also, the number of COVID-19 cases in hospitals is higher than at the peak of the first wave in April 2020. The effects of easing of social distancing when we transition out of lockdown need to be closely monitored to avoid a resurgence in infections and renewed pressure on health services.

REACT-1 round 8 final report: high average prevalence with regional heterogeneity of trends in SARS-CoV-2 infection in the community in England during January 2021

In early January 2021, England entered its third national lockdown of the COVID-19 pandemic to reduce numbers of deaths and pressure on healthcare services, while rapidly rolling out vaccination to healthcare workers and those most at risk of severe disease and death. REACT-1 is a survey of SARS-CoV-2 prevalence in the community in England, based on repeated cross-sectional samples of the population. Between 6th and 22nd January 2021, out of 167,642 results, 2,282 were positive giving a weighted national prevalence of infection of 1.57% (95% CI, 1.49%, 1.66%). The R number nationally over this period was estimated at 0.98 (0.92, 1.04). Prevalence remained high throughout, but with suggestion of a decline at the end of the study period. The average national trend masked regional heterogeneity, with robustly decreasing prevalence in one region (South West) and increasing prevalence in another (East Midlands). Overall prevalence at regional level was highest in London at 2.83% (2.53%, 3.16%). Although prevalence nationally was highest in the low-risk 18 to 24 year old group at 2.44% (1.96%, 3.03%), it was also high in those over 65 years who are most at risk, at 0.93% (0.82%, 1.05%). Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with higher levels of infections compared to smaller households, less deprived neighbourhoods and other ethnicities. Healthcare and care home workers, and other key workers, were more likely to test positive compared to other workers. If sustained lower prevalence is not achieved rapidly in England, pressure on healthcare services and numbers of COVID-19 deaths will remain unacceptably high.

REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England

BackgroundHigh prevalence of SARS-CoV-2 virus in many northern hemisphere populations is causing extreme pressure on healthcare services and leading to high numbers of fatalities. Even though safe and effective vaccines are being deployed in many populations, the majority of those most at-risk of severe COVID-19 will not be protected until late spring, even in countries already at a more advanced stage of vaccine deployment. MethodsThe REal-time Assessment of Community Transmission study-1 (REACT-1) obtains throat and nose swabs from between 120,000 and 180,000 people in the community in England at approximately monthly intervals. Round 8a of REACT-1 mainly covers a period from 6th January 2021 to 15th January 2021. Swabs are tested for SARS-CoV-2 virus and patterns of swab-positivity are described over time, space and with respect to individual characteristics. We compare swab-positivity prevalence from REACT-1 with mobility data based on the GPS locations of individuals using the Facebook mobile phone app. We also compare results from round 8a with those from round 7 in which swabs were collected from 13th November to 24th November (round 7a) and 25th November to 3rd December 2020 (round 7b). ResultsIn round 8a, we found 1,962 positives from 142,909 swabs giving a weighted prevalence of 1.58% (95% CI, 1.49%, 1.68%). Using a constant growth model, we found no strong evidence for either growth or decay averaged across the period; rather, based on data from a limited number of days, prevalence may have started to rise at the end of round 8a. Facebook mobility data showed a marked decrease in activity at the end of December 2020, followed by a rise at the start of the working year in January 2021. Between round 7b and round 8a, prevalence increased in all adult age groups, more than doubling to 0.94% (0.83%, 1.07%) in those aged 65 and over. Large household size, living in a deprived neighbourhood, and Black and Asian ethnicity were all associated with increased prevalence. Both healthcare and care home workers, and other key workers, had increased odds of swab-positivity compared to other workers. ConclusionDuring the initial 10 days of the third COVID-19 lockdown in England in January 2021, prevalence of SARS-CoV-2 was very high with no evidence of decline. Until prevalence in the community is reduced substantially, health services will remain under extreme pressure and the cumulative number of lives lost during this pandemic will continue to increase rapidly.

REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England

BackgroundEngland exited a four-week second national lockdown on 2nd December 2020 initiated in response to the COVID-19 pandemic. Prior results showed that prevalence dropped during the first half of lockdown, with greater reductions in higher-prevalence northern regions. MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England, designed to monitor the spread of the epidemic and thus increase situational awareness. Round 7 of REACT-1 commenced swab-collection on 13th November 2020. A prior interim report included data from 13th to 24th November 2020 for 105,122 participants. Here, we report data for the entire round with swab results obtained up to 3rd December 2020. ResultsBetween 13th November and 3rd December (round 7) there were 1,299 positive swabs out of 168,181 giving a weighted prevalence of 0.94% (95% CI 0.87%, 1.01%) or 94 per 10,000 people infected in the community in England. This compares with a prevalence of 1.30% (1.21%, 1.39%) from 16th October to 2nd November 2020 (round 6), a decline of 28%. Prevalence during the latter half of round 7 was 0.91% (95% CI, 0.81%, 1.03%) compared with 0.96% (0.87%, 1.05%) in the first half. The national R number in round 7 was estimated at 0.96 (0.88, 1.03) with a decline in prevalence observed during the first half of this period no longer apparent during the second half at the end of lockdown. During round 7 there was a marked fall in prevalence in West Midlands, a levelling off in some regions and a rise in London. R numbers at regional level ranged from 0.60 (0.41, 0.80) in West Midlands up to 1.27 (1.04, 1.54) in London, where prevalence was highest in the east and south-east of the city. Nationally, between 13th November and 3rd December, the highest prevalence was in school-aged children especially at ages 13-17 years at 2.04% (1.69%, 2.46%), or approximately 1 in 50. ConclusionBetween the previous round and round 7 (during lockdown), there was a fall in prevalence of SARS-CoV-2 swab-positivity nationally, but it did not fall uniformly over time or by geography. Continued vigilance is required to reduce rates of infection until effective immunity at the population level can be achieved through the vaccination programme.

REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020

BackgroundEngland is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020. MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020. ResultsOverall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2%), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South. ConclusionThe impact of the second national lockdown in England is not yet known. We provide here a detailed description of swab-positivity patterns at national, regional and local scales for the period immediately preceding lockdown, against which future trends in prevalence can be evaluated.

High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report

BackgroundREACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive. MethodsREACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive. ResultsOverall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%). ConclusionThe co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.

Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults

BackgroundThe prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity. MethodsPrevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed. ResultsThere were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, -23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: -14.9% [-21.6, -8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: -39.0% [-50.8, -27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]). The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (-64.0% [-75.6, -52.3]), compared to -22.3% ([-27.0, -17.7]) in those with SARS-CoV-2 infection confirmed on PCR. DiscussionThese findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of reinfection as detectable antibodies decline in the population.

High and increasing prevalence of SARS-CoV-2 swab positivity in England during end September beginning October 2020: REACT-1 round 5 updated report

BackgroundREACT-1 is quantifying prevalence of SARS-CoV-2 infection among random samples of the population in England based on PCR testing of self-administered nose and throat swabs. Here we report results from the fifth round of observations for swabs collected from the 18th September to 5th October 2020. This report updates and should be read alongside our round 5 interim report. MethodsRepresentative samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 175,000 people at each round. Prevalence of PCR-confirmed SARS-CoV-2 infection, estimation of reproduction number (R) and time trends between and within rounds using exponential growth or decay models. Results175,000 volunteers tested across England between 18th September and 5th October. Findings show a national prevalence of 0.60% (95% confidence interval 0.55%, 0.71%) and doubling of the virus every 29 (17, 84) days in England corresponding to an estimated national R of 1.16 (1.05, 1.27). These results correspond to 1 in 170 people currently swab-positive for the virus and approximately 45,000 new infections each day. At regional level, the highest prevalence is in the North West, Yorkshire and The Humber and the North East with strongest regional growth in North West, Yorkshire and The Humber and West Midlands. ConclusionRapid growth has led to high prevalence of SARS-CoV-2 virus in England, with highest rates in the North of England. Prevalence has increased in all age groups, including those at highest risk. Improved compliance with existing policy and, as necessary, additional interventions are required to control the spread of SARS-CoV-2 in the community and limit the numbers of hospital admissions and deaths from COVID-19.

High prevalence of SARS-CoV-2 swab positivity in England during September 2020: interim report of round 5 of REACT-1 study

BackgroundREACT-1 is a community survey of PCR confirmed swab-positivity for SARS-CoV-2 among random samples of the population in England. This interim report includes data from the fifth round of data collection currently underway for swabs sampled from the 18th to 26th September 2020. MethodsRepeated cross-sectional surveys of random samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 160,000 people in each round of data collection. Collection of self-administered nose and throat swab for PCR and questionnaire data. Prevalence of swab-positivity by round and by demographic variables including age, sex, region, ethnicity. Estimation of reproduction number (R) between and within rounds, and time trends using exponential growth or decay model. Assessment of geographical clustering based on boundary-free spatial model. ResultsOver the 9 days for which data are available, we find 363 positives from 84,610 samples giving a weighted prevalence to date of 0.55% (0.47%, 0.64%) in round 5. This implies that 411,000 (351,000, 478,000) people in England are virus-positive under the assumption that the swab assay is 75% sensitive. Using data from the most recent two rounds, we estimate a doubling time of 10.6 (9.4, 12.0) days covering the period 20th August to 26th September, corresponding to a reproduction number R of 1.47 (1.40, 1.53). Using data only from round 5 we estimate a reproduction number of 1.06 (0.74, 1.46) with probability of 63% that R is greater than 1. Between rounds 4 and 5 there was a marked increase in unweighted prevalence at all ages. In the most recent data, prevalence was highest in the 18 to 24 yrs age group at 0.96% (0.68%, 1.36%). At 65+ yrs prevalence increased [~]7-fold between rounds 4 and 5 from 0.04% (0.03%, 0.07%) to 0.29% (0.23%, 0.37%). Prevalence increased in all regions between rounds 4 and 5, giving the highest unweighted prevalence in round 5 in the North West at 0.86% (0.69%, 1.06%). In London, prevalence increased [~]5-fold from 0.10% (0.06%, 0.17%) to 0.49% (0.36%, 0.68%). Regional R values ranged from 1.32 (1.16,1.50) in Yorkshire and the Humber to 1.63 (1.42, 1.88) in the East Midlands over the same period. In the most recent data, there was extensive clustering in the North West, Midlands and in and around London with pockets of clustering in other regions including the South West, North East and East of England. Odds of swab-positivity were [~]2-fold higher in people of Asian and Black ethnicity compared with white participants. ConclusionRapid growth has led to high prevalence of SARS-CoV-2 virus in England among all regions and age groups, including those age groups at highest risk. Although there is evidence of a recent deceleration in the epidemic, current levels of prevalence will inevitably result in additional hospitalisations and mortality in coming weeks. A re-doubling of public health efforts is needed to return to a declining phase of the epidemic.

Resurgence of SARS-CoV-2 in England: detection by community antigen surveillance

Background Based on cases and deaths, transmission of SARS-CoV-2 in England peaked in late March and early April 2020 and then declined until the end of June. Since the start of July, cases have increased, while deaths have continued to decrease. Methods We report results from 594,000 swabs tested for SARS-CoV-2 virus obtained from a representative sample of people in England over four rounds collected regardless of symptoms, starting in May 2020 and finishing at the beginning of September 2020. Swabs for the most recent two rounds were taken between 24th July and 11th August and for round 4 between 22nd August and 7th September. We estimate weighted overall prevalence, doubling times between and within rounds and associated reproduction numbers. We obtained unweighted prevalence estimates by sub-groups: age, sex, region, ethnicity, key worker status, household size, for which we also estimated odds of infection. We identified clusters of swab-positive participants who were closer, on average, to other swab-positive participants than would be expected. Findings Over all four rounds of the study, we found that 72% (67%, 76%) of swab-positive individuals were asymptomatic at the time of swab and in the week prior. The epidemic declined between rounds 1 and 2, and rounds 2 and 3. However, the epidemic was increasing between rounds 3 and 4, with a doubling time of 17 (13, 23) days corresponding to an R value of 1.3 (1.2, 1.4). When analysing round 3 alone, we found that the epidemic had started to grow again with 93% probability. Using only the most recent round 4 data, we estimated a doubling time of 7.7 (5.5, 12.7) days, corresponding to an R value of 1.7 (1.4, 2.0). Cycle threshold values were lower (viral loads were higher) for rounds 1 and 4 than they were for rounds 2 and 3. In round 4, we observed the highest prevalence in participants aged 18 to 24 years at 0.25% (0.16%, 0.41%), increasing from 0.08% (0.04%, 0.18%) in round 3. We observed the lowest prevalence in those aged 65 and older at 0.04% (0.02%, 0.06%) which was stable compared with round 3. Participants of Asian ethnicity had elevated odds of infection. We identified clusters in and around London, transient clusters in the Midlands, and an expanding area of clustering in the North West and more recently in Yorkshire and the Humber. Interpretation Although low levels of transmission persisted in England through to mid-summer 2020, the prevalence of SARS-CoV-2 is now increasing. We found evidence of accelerating transmission at the end of August and beginning of September. Representative community antigen sampling can increase situational awareness and help improve public health decision making even at low prevalence.