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Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy and will be a high priority for public health for the foreseeable future. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained using a variety of methods all of which are known to contain biases. As a case study, using an approach which is largely free of biases, we here describe lineage dynamics and phylogenetic relationships of the Alpha and Beta variant in England during the first 3 months of 2021 using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the Alpha variant (first identified in Kent) becoming predominant, driven by a reproduction number 0.3 higher than for the prior wild-type. During January, positive samples were more likely to be Alpha in those aged 18 to 54 years old. Although individuals infected with the Alpha variant were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild-type, they were more likely to be antibody-positive 6 weeks after infection. Further, viral load was higher in those infected with the Alpha variant as measured by cycle threshold (Ct) values. The presence of infections with non-imported Beta variant (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing. These results highlight how sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance during periods of lineage diversity.

Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

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=1,047, 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.

Background The third wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron variant. However, rates of hospitalisations and deaths were substantially lower than in the first and second waves 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 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 1,195 positive samples with sublineages determined, only one (0.1% [0.0–0.5]) corresponded to AY.39 Delta sublineage and the remainder were Omicron: N=390, 32.7% (30.0–35.4) were BA.1; N=473, 39.6% (36.8–42.5) were BA.1.1; and N=331, 27.7% (25.2–30.4) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1 or BA.1.1) of 0.40 (0.36–0.43). 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.

Background: Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highest ever recorded case incidence levels in many countries around the world. Methods: The REal-time Assessment of Community Transmission-1 (REACT-1) study has been characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results from self-administered throat and nose swabs from randomly-selected participants in England at ages 5 years and over, approximately monthly since May 2020. Round 17 data were collected between 5 and 20 January 2022 and provide data on the temporal, socio-demographic and geographical spread of the virus, viral loads and viral genome sequence data for positive swabs. Results: From 102,174 valid tests in round 17, weighted prevalence of swab positivity was 4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than in December 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages were determined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages) cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022, and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1 and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03, 0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92). Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years and older had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a high level of infection among a highly vulnerable group. Among the 3,613 swab-positive individuals reporting whether or not they had had previous infection, 2,334 (64.6%) reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to 30 days before their swab date. Risks of infection were increased among essential/key workers (other than healthcare or care home workers) with mutually adjusted Odds Ratio (OR) of 1.15 (95% CI, 1.05, 1.26), people living in large compared to single-person households (6+ household size OR 1.73; 95% CI, 1.44, 2.08), those living in urban vs rural areas (OR 1.24, 95% CI, 1.13, 1.35) and those living in the most vs least deprived areas (OR 1.34, 95% CI, 1.20, 1.49). Conclusions: We observed unprecedented levels of infection with SARS-CoV-2 in England in January 2022, an almost complete replacement of Delta by Omicron, and evidence for a growth advantage for BA.2 compared to BA.1. The increase in the prevalence of infection with Omicron among children (aged 5 to 17 years) during January 2022 could pose a risk to adults, despite the current trend for prevalence in adults to decline. (Funded by the Department of Health and Social Care in England.)

Background: The highest-ever recorded numbers of daily severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in England has been observed during December 2021 and have coincided with a rapid rise in the highly transmissible Omicron variant despite high levels of vaccination in the population. Although additional COVID-19 measures have been introduced in England and internationally to contain the epidemic, there remains uncertainty about the spread and severity of Omicron infections among the general population. Methods: The REal-time Assessment of Community Transmission–1 (REACT-1) study has been monitoring the prevalence of SARS-CoV-2 infection in England since May 2020. REACT-1 obtains self-administered throat and nose swabs from a random sample of the population of England at ages 5 years and over. Swabs are tested for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) and samples testing positive are sent for viral genome sequencing. To date 16 rounds have been completed, each including ~100,000 or more participants with data collected over a period of 2 to 3 weeks per month. Socio-demographic, lifestyle and clinical information (including previous history of COVID-19 and symptoms prior to swabbing) is collected by online or telephone questionnaire. Here we report results from round 14 (9-27 September 2021), round 15 (19 October - 05 November 2021) and round 16 (23 November - 14 December 2021) for a total of 297,728 participants with a valid RT-PCR test result, of whom 259,225 (87.1%) consented for linkage to their NHS records including detailed information on vaccination (vaccination status, date). We used these data to estimate community prevalence and trends by age and region, to evaluate vaccine effectiveness against infection in children ages 12 to 17 years, and effect of a third (booster) dose in adults, and to monitor the emergence of the Omicron variant in England. Results: We observed a high overall prevalence of 1.41% (1.33%, 1.51%) in the community during round 16. We found strong evidence of an increase in prevalence during round 16 with an estimated reproduction number R of 1.13 (1.06, 1.09) for the whole of round 16 and 1.27 (1.14, 1.40) when restricting to observations from 1 December onwards. The reproduction number in those aged 18-54 years was estimated at 1.23 (1.14, 1.33) for the whole of round 16 and 1.41 (1.23, 1.61) from 1 December. Our data also provide strong evidence of a steep increase in prevalence in London with an estimated R of 1.62 (1.34, 1.93) from 1 December onwards and a daily prevalence reaching 6.07% (4.06%, 9.00%) on 14 December 2021. As of 1 to 11 December 2021, of the 275 lineages determined, 11 (4.0%) corresponded to the Omicron variant. The first Omicron infection was detected in London on 3 December, and subsequent infections mostly appeared in the South of England. The 11 Omicron cases were all aged 18 to 54 years, double-vaccinated (reflecting the large numbers of people who have received two doses of vaccine in this age group) but not boosted, 9 were men, 5 lived in London and 7 were symptomatic (5 with classic COVID-19 symptoms: loss or change of sense of smell or taste, fever, persistent cough), 2 were asymptomatic, and symptoms were unknown for 2 cases. The proportion of Omicron (vs Delta or Delta sub-lineages) was found to increase rapidly with a daily increase of 66.0% (32.7%, 127.3%) in the odds of Omicron (vs. Delta) infection, conditional on swab positivity. Highest prevalence of swab positivity by age was observed in (unvaccinated) children aged 5 to 11 years (4.74% [4.15%, 5.40%]) similar to the prevalence observed at these ages in round 15. In contrast, prevalence in children aged 12 to 17 years more than halved from 5.35% (4.78%, 5.99%) in round 15 to 2.31% (1.91%, 2.80%) in round 16. As of 14 December 2021, 76.6% children at ages 12 to 17 years had received at least one vaccine dose; we estimated that vaccine effectiveness against infection was 57.9% (44.1%, 68.3%) in this age group. In addition, the prevalence of swab positivity in adults aged 65 years and over fell by over 40% from 0.84% (0.72%, 0.99%) in round 15 to 0.48% (0.39%,0.59%) in round 16 and for those aged 75 years and over it fell by two-thirds from 0.63% (0.48%,0.82%) to 0.21% (0.13%,0.32%). At these ages a high proportion of participants (>90%) had received a third vaccine dose; we estimated that adults having received a third vaccine dose had a three- to four-fold lower risk of testing positive compared to those who had received two doses. Conclusion: A large fall in swab positivity from round 15 to round 16 among 12 to 17 year olds, most of whom have been vaccinated, contrasts with the continuing high prevalence among 5 to 11 year olds who have largely not been vaccinated. Likewise there were large falls in swab positivity among people aged 65 years and over, the vast majority of whom have had a third (booster) vaccine dose; these results reinforce the importance of the vaccine and booster campaign. However, the rapidly increasing prevalence of SARS-CoV-2 infections in England during December 2021, coincident with the rapid rise of Omicron infections, may lead to renewed pressure on health services. Additional measures beyond vaccination may be needed to control the current wave of infections and prevent health services (in England and other countries) from being overwhelmed.

Background: It has been nearly a year since the first vaccinations against SARS-CoV-2 were delivered in England. The third wave of COVID-19 in England began in May 2021 as the Delta variant began to outcompete and largely replace other strains. The REal-time Assessment of Community Transmission-1 (REACT-1) series of community surveys for SARS-CoV-2 infection has provided insights into transmission dynamics since May 2020. Round 15 of the REACT-1 study was carried out from 19 October to 5 November 2021. Methods: We estimated prevalence of SARS-CoV2 infection and used multiple logistic regression to analyse associations between SARS-CoV-2 infection in England and demographic and other risk factors, based on RT-PCR results from self-administered throat and nose swabs in over 100,000 participants. We estimated (single-dose) vaccine effectiveness among children aged 12 to 17 years, and among adults compared swab-positivity in people who had received a third (booster) dose with those who had received two vaccine doses. We used splines to analyse time trends in swab-positivity. Results: During mid-October to early-November 2021, weighted prevalence was 1.57% (1.48%, 1.66%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). Weighted prevalence increased between rounds 14 and 15 across most age groups (including older ages, 65 years and over) and regions, with average reproduction number across rounds of R=1.09 (1.08, 1.11). During round 15, there was a fall in prevalence from a maximum around 20-21 October, with an R of 0.76 (0.70, 0.83), reflecting falls in prevalence at ages 17 years and below and 18 to 54 years. School-aged children had the highest weighted prevalence of infection: 4.95% (4.39%, 5.58%) in those aged 5 to 12 years and 5.21% (4.61%, 5.87%) in those aged 13 to 17 years. In multiple logistic regression, age, sex, key worker status and presence of one or more children in the home were associated with swab positivity. There was evidence of heterogeneity between rounds in swab positivity rates among vaccinated individuals at ages 18 to 64 years, and differences in key demographic and other variables between vaccinated and unvaccinated adults at these ages. Vaccine effectiveness against infection in children was estimated to be 56.2% (41.3%, 67.4%) in rounds 13, 14 and 15 combined, adjusted for demographic factors, with a similar estimate obtained for round 15 only. Among adults we found that those who received a third dose of vaccine were less likely to test positive compared to those who received only two vaccine doses, with adjusted odds ratio (OR) =0.38 (0.26, 0.55). Discussion: Swab-positivity was very high at the start of round 15, reaching a maximum around 20 to 21 October 2021, and then falling through late October with an uncertain trend in the last few days of data collection. The observational nature of survey data and the relatively small proportion of unvaccinated adults call into question the comparability of vaccinated and unvaccinated groups at this relatively late stage in the vaccination programme. However, third vaccine doses for eligible adults and the vaccination of children aged 12 years and over are associated with lower infection risk and, thus, remain a high priority (with possible extension to children aged 5-12 years). These should help reduce SARS-CoV-2 transmission during the winter period when healthcare demands typically rise.

Background: The third wave of COVID-19 in England coincided with the rapid spread of the Delta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from the national testing programme (Pillar 2) in England may be affected by changes in testing behaviour and other biases. Community surveys may provide important contextual information to inform policy and the public health response. Methods: We estimated patterns of community prevalence of SARS-CoV-2 infection in England using RT-PCR swab-positivity, demographic and other risk factor data from round 15 (interim) of the REal-time Assessment of Community Transmission-1 (REACT-1) study (round 15a, carried out from 19 to 29 October 2021). We compared these findings with those from round 14 (9 to 27 September 2021). Results: During mid- to late-October 2021 (round 15a) weighted prevalence was 1.72% (1.61%, 1.84%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). The overall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) with increases in prevalence over this period (September to October) across age groups and regions except Yorkshire and The Humber. However, within round 15a (mid- to late-October) there was evidence of a fall in prevalence with R of 0.76 (0.65, 0.88). The highest weighted prevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and 13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-fold increase in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) to round 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional level also found in South West in round 15a. Age, sex, key worker status, and presence of children in the home jointly contributed to the risk of swab-positivity. Among the 126 sequenced positive swabs obtained up until 23 October, all were Delta variant; 13 (10.3%) were identified as the AY.4.2 sub-lineage. Discussion: We observed the highest overall prevalence of swab-positivity seen in the REACT-1 study in England to date in round 15a (October 2021), with a two-fold rise in swab-positivity from round 14 (September 2021). Despite evidence of a fall in prevalence from mid- to late-October 2021, prevalence remains high, particularly in school-aged children, with evidence also of higher prevalence in households with one or more children. Thus, vaccination of children aged 12 and over remains a high priority (with possible extension to children aged 5-12) to help reduce within-household transmission and disruptions to education, as well as among adults, to lessen the risk of serious disease among those infected.

Background: England experienced a third wave of the COVID-19 epidemic from end May 2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible for vaccination against COVID-19 has been extended to include all 12-15-year-olds, and a booster programme has been initiated among adults aged 50 years and over, health care and care home workers, and immunocompromised people. Meanwhile, schoolchildren have returned to school often with few COVID-19-related precautions in place. Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study, throat and nose swabs were sent to non-overlapping random samples of the population aged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round 14 (between 9 and 27 September 2021). We combined results for round 14 with round 13 (between 24 June and 12 July 2021) and estimated vaccine effectiveness and prevalence of swab-positivity among double-vaccinated individuals. Unlike all previous rounds, in round 14, we switched from dry swabs transported by courier on a cold chain to wet swabs using saline. Also, at random, 50% of swabs (not chilled until they reached the depot) were transported by courier and 50% were sent through the priority COVID-19 postal service. Results: We observed stable or rising prevalence (with an R of 1.03 (0.94, 1.14) overall) during round 14 with a weighted prevalence of 0.83% (0.76%, 0.89%). The highest weighted prevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17 years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Delta variant or sub-lineages of Delta with one instance of the E484K escape mutation detected. The epidemic was growing in those aged 17 years and under with an R of 1.18 (1.03, 1.34), but decreasing in those aged 18 to 54 years with an R of 0.81 (0.68, 0.97). For all participants and all vaccines combined, vaccine effectiveness against infection (rounds 13 and 14 combined) was estimated to be 62.8% (49.3%, 72.7%) after two doses compared to unvaccinated people when adjusted for round, age, sex, index of multiple deprivation, region and ethnicity; the adjusted estimate was 44.8% (22.5%, 60.7%) for AstraZeneca and 71.3% (56.6%, 81.0%) for Pfizer-BioNTech, and for all vaccines combined it was 66.4% (49.6%, 77.6%) against symptomatic infection (one or more of 26 surveyed symptoms in month prior). Across rounds 13 and 14, weighted prevalence of swab-positivity was 0.55% (0.50%, 0.61%) for those who received their second dose 3-6 months before their swab compared to 0.35% (0.31%, 0.40%) for those whose second dose was within 3 months of their swab. However, the prevalence was lower in those with one or two doses of vaccine than in unvaccinated individuals at 1.76% (1.60%, 1.95%). In round 14, age group, region, key worker status, and household size jointly contributed to the risk of higher prevalence of swab-positivity. Discussion: In September 2021 infections were increasing exponentially in the 5-to-17-year age group coinciding with the start of the autumn school term in England. Relatively few schoolchildren aged 5 to 17 years have been vaccinated in the UK though single doses are now being offered to those aged 12 years and over. In adults, the higher prevalence of swab-positivity following two doses of vaccine within 3 to 6 months supports the use of a booster vaccine. It is important that the vaccination programme maintains high coverage and reaches children and unvaccinated or partially vaccinated adults to reduce transmission and associated disruptions to work and education.

Background Community surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administered throat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community. Methods During round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines. Results We estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportion of positive individuals detected on first swab, was found to be higher 𝑃 for those with an 0 initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in social distancing measures. Discussion Home self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has high overall sensitivity. However, participants' time-since-infection, symptom status and viral lineage affect the probability of detection and the duration of positivity. These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data, and provide a reliable means to obtain community infection estimates to inform policy response.

Background The prevalence of SARS-CoV-2 infection continues to drive rates of illness and hospitalisations despite high levels of vaccination, with the proportion of cases caused by the Delta lineage increasing in many populations. As vaccination programs roll out globally and social distancing is relaxed, future SARS-CoV-2 trends are uncertain. Methods We analysed prevalence trends and their drivers using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June 2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment of Community Transmission-1 (REACT-1) study, with swabs sent to non-overlapping random samples of the population ages 5 years and over in England. Results We observed sustained exponential growth with an average doubling time in round 13 of 25 days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15% (0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth across and within rounds appears to have been driven by complete replacement of Alpha variant by Delta, and by the high prevalence in younger less-vaccinated age groups, with a nine-fold increase between rounds 12 and 13 among those aged 13 to 17 years. Prevalence among those who reported being unvaccinated was three-fold higher than those who reported being fully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinated individuals, reflecting imperfect vaccine effectiveness against infection despite high overall levels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccine effectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18 to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cycle threshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness against symptomatic infection of 59% (23%, 78%), with any one of three common COVID-19 symptoms reported in the month prior to swabbing. Sex (round 13 only), ethnicity, household size and local levels of deprivation jointly contributed to the risk of higher prevalence of swab-positivity. Discussion From end May to beginning July 2021 in England, where there has been a highly successful vaccination campaign with high vaccine uptake, infections were increasing exponentially driven by the Delta variant and high infection prevalence among younger, unvaccinated individuals despite double vaccination continuing to effectively reduce transmission. Although slower growth or declining prevalence may be observed during the summer in the northern hemisphere, increased mixing during the autumn in the presence of the Delta variant may lead to renewed growth, even at high levels of vaccination.

Background Despite 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. Methods We 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. Results In 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. Discussion We 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.

Background England entered a third national lockdown from 6 January 2021 due to the COVID-19 pandemic. Despite a successful vaccine rollout during the first half of 2021, cases and hospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta (B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19 restrictions in England has been delayed from 21 June to 19 July 2021. Methods The REal-time Assessment of Community Transmision-1 (REACT-1) study measures the prevalence of swab-positivity among random samples of the population of England. Round 12 of REACT-1 obtained self-administered swab collections from participants from 20 May 2021 to 7 June 2021; results are compared with those for round 11, in which swabs were collected from 15 April to 3 May 2021. Results Between rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to 0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doubling time of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence was found in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in the South West. In the North West, the locations of positive samples suggested a cluster in Greater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection rates and hospitalisations and deaths started to weaken, although in late April 2021, infection rates and hospital admissions started to reconverge. When split by age, the weakened link between infection rates and hospitalisations at ages 65 years and above was maintained, while the trends converged below the age of 65 years. The majority of the infections in the younger group occurred in the unvaccinated population or those without a stated vaccine history. We observed the rapid replacement of the Alpha (B.1.1.7) variant of SARS-CoV-2 with the Delta variant during the period covered by rounds 11 and 12 of the study. Discussion The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.

Background National epidemic dynamics of SARS-CoV-2 infections are being driven by: the degree of recent indoor mixing (both social and workplace), vaccine coverage, intrinsic properties of the circulating lineages, and prior history of infection (via natural immunity). In England, infections, hospitalisations and deaths fell during the first two steps of the “roadmap” for exiting the third national lockdown. The third step of the roadmap in England takes place on 17 May 2021. Methods We report the most recent findings on community infections from the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a swab is obtained from a representative cross-sectional sample of the population in England and tested using PCR. Round 11 of REACT-1 commenced self-administered swab-collection on 15 April 2021 and completed collections on 3 May 2021. We compare the results of REACT-1 round 11 to round 10, in which swabs were collected from 11 to 30 March 2021. Results Between rounds 10 and 11, prevalence of swab-positivity dropped by 50% in England from 0.20% (0.17%, 0.23%) to 0.10% (0.08%, 0.13%), with a corresponding R estimate of 0.90 (0.87, 0.94). Rates of swab-positivity fell in the 55 to 64 year old group from 0.17% (0.12%, 0.25%) in round 10 to 0.06% (0.04%, 0.11%) in round 11. Prevalence in round 11 was higher in the 25 to 34 year old group at 0.21% (0.12%, 0.38%) than in the 55 to 64 year olds and also higher in participants of Asian ethnicity at 0.31% (0.16%, 0.60%) compared with white participants at 0.09% (0.07%, 0.11%). Based on sequence data for positive samples for which a lineage could be identified, we estimate that 92.3% (75.9%, 97.9%, n=24) of infections were from the B.1.1.7 lineage compared to 7.7% (2.1%, 24.1%, n=2) from the B.1.617.2 lineage. Both samples from the B.1.617.2 lineage were detected in London from participants not reporting travel in the previous two weeks. Also, allowing for suitable lag periods, the prior close alignment between prevalence of infections and hospitalisations and deaths nationally has diverged. Discussion We observed marked reductions in prevalence from March to April and early May 2021 in England reflecting the success of the vaccination programme and despite easing of restrictions during lockdown. However, there is potential upwards pressure on prevalence from the further easing of lockdown regulations and presence of the B.1.617.2 lineage. If prevalence rises in the coming weeks, policy-makers will need to assess the possible impact on hospitalisations and deaths. In addition, consideration should be given to other health and economic impacts if increased levels of community transmission occur.

Background In 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. Methods The 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. Results During 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. Conclusion We 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.

Background England 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. Methods The 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. Results Out 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 one third 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. Conclusions Community 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.

Background and Methods: England 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. Results: Out 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. Conclusions: There 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.

Background: The REal-time Assessment of Community Transmission-1 (REACT-1) study has provided unbiased estimates of swab-positivity in England approximately monthly since May 2020 using RT-PCR testing of self-administered throat and nose swabs. However, estimating infection incidence requires an understanding of the persistence of RT-PCR swab-positivity in the community. Methods: During round 8 of REACT-1 from 6 January to 22 January 2021, we collected up to two additional swabs from 896 initially RT-PCR positive individuals approximately 6 and 9 days after their initial swab. Results: Test sensitivity and duration of positivity were estimated using an exponential decay model, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. A P-spline model was used to estimate infection incidence for the entire duration of the REACT-1 study. REACT-1 test sensitivity was estimated at 0.79 (0.77, 0.81) with median duration of positivity at 9.7 (8.9, 10.6) days. We found greater duration of positivity in those exhibiting symptoms, with low N-gene Ct values, or infected with the Alpha variant. Test sensitivity was found to be higher for those who were pre-symptomatic or with low N-gene Ct values. Compared to swab-positivity, our estimates of infection incidence included sharper features with evident transient increases around the time of changes in social distancing measures. Conclusions: These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data and provide a reliable means to obtain community infection estimates to inform policy response.

There is a trade-off between the education sector and other economic sectors in the control of SARS-Cov-2 transmission. Here we integrate a dynamic model of SARS-CoV-2 transmission with a 63-sector economic model reflecting sectoral heterogeneity in transmission and economic interdependence between sectors. We identify COVID-19 control strategies which optimize economic production while keeping schools and universities operational and constraining infections such that emergency hospital capacity is not exceeded. The model estimates an economic gain of between £163bn and £205bn for the United Kingdom compared to a blanket lockdown of non-essential activity over six months, depending on hospital capacity. Sectors identified as potential priorities for closure are contact-intensive and/or less economically productive.

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for

Following ini􀀂al declines, in mid 2020, a resurgence in transmission of novel coronavirus disease (COVID-19) has occurred in the United States and parts of Europe. Despite the wide implementa􀀂on of non-pharmaceu􀀂cal inter-ven􀀂ons, it is s􀀂ll not known how they are impacted by changing contact pa􀀁erns, age and other demographics. As COVID-19 disease control becomes more localised, understanding the age demographics driving transmission and how these impact the loosening of interven􀀂ons such as school reopening is crucial. Considering dynamics for the United States, we analyse aggregated, age-specific mobility trends from more than 10 million individuals and link these mechanis􀀂cally to age-specific COVID-19 mortality data. In contrast to previous approaches, we link mobility to mortality via age specific contact pa􀀁erns and use this rich rela􀀂onship to reconstruct accurate trans-mission dynamics. Contrary to anecdotal evidence, we find li􀀁le support for age-shi􀀃s in contact and transmission dynamics over 􀀂me. We es􀀂mate that, un􀀂l August, 63.4% [60.9%-65.5%] of SARS-CoV-2 infec􀀂ons in the United States originated from adults aged 20-49, while 1.2% [0.8%-1.8%] originated from children aged 0-9. In areas with con􀀂nued, community-wide transmission, our transmission model predicts that re-opening kindergartens and el-ementary schools could facilitate spread and lead to considerable excess COVID-19 a􀀁ributable deaths over a 90-day period. These findings indicate that targe􀀂ng interven􀀂ons to adults aged 20-49 are an important con-sidera􀀂on in hal􀀂ng resurgent epidemics, and preven􀀂ng COVID-19-a􀀁ributable deaths when kindergartens and elementary schools reopen.

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported substantially lower mortality rates than in Europe and the Americas. One hypothesis is that these countries have been ‘spared’, but another is that deaths have been under-ascertained (deaths that have been unreported due to any number of reasons, for instance due to limited testing capacity). However, the scale of under-ascertainment is difficult to assess with currently available data. In this analysis, we estimate the potential under-ascertainment of COVID-19 mortality in Damascus, Syria, where all-cause mortality data has been reported between 25th July and 1st August. We fit a mathematical model of COVID-19 transmission to reported COVID-19 deaths in Damascus since the beginning of the pandemic and compare the model-predicted deaths to reported excess deaths. Exploring a range of different assumptions about under-ascertainment, we estimate that only 1.25% of deaths (sensitivity range 1% - 3%) due to COVID-19 are reported in Damascus. Accounting for under-ascertainment also corroborates local reports of exceeded hospital bed capacity. To validate the epidemic dynamics inferred, we leverage community-uploaded obituary certificates as an alternative data source, which confirms extensive mortality under-ascertainment in Damascus between July and August. This level of under-ascertainment suggests that Damascus is at a much later stage in its epidemic than suggested by surveillance reports, which have repo. We estimate that 4,340 (95% CI: 3,250 - 5,540) deaths due to COVID-19 in Damascus may have been missed as of 2nd September 2020. Given that Damascus is likely to have the most robust surveillance in Syria, these findings suggest that other regions of the country could have experienced similar or worse mortality rates due to COVID-19.

Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings. Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic. Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC

COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely high health system demand; for TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic. In high burden settings, the impact of each type of disruption could be significant and lead to a loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.

The world faces a severe and acute public health emergency due to the ongoing COVID-19 global pandemic. How individual countries respond in the coming weeks will be critical in influencing the trajectory of national epidemics. Here we combine data on age-specific contact patterns and COVID-19 severity to project the health impact of the pandemic in 202 countries. We compare predicted mortality impacts in the absence of interventions or spontaneous social distancing with what might be achieved with policies aimed at mitigating or suppressing transmission. Our estimates of mortality and healthcare demand are based on data from China and high-income countries; differences in underlying health conditions and healthcare system capacity will likely result in different patterns in low income settings. We estimate that in the absence of interventions, COVID-19 would have resulted in 7.0 billion infections and 40 million deaths globally this year. Mitigation strategies focussing on shielding the elderly (60% reduction in social contacts) and slowing but not interrupting transmission (40% reduction in social contacts for wider population) could reduce this burden by half, saving 20 million lives, but we predict that even in this scenario, health systems in all countries will be quickly overwhelmed. This effect is likely to be most severe in lower income settings where capacity is lowest: our mitigated scenarios lead to peak demand for critical care beds in a typical low-income setting outstripping supply by a factor of 25, in contrast to a typical high-income setting where this factor is 7. As a result, we anticipate that the true burden in low income settings pursuing mitigation strategies could be substantially higher than reflected in these estimates. Our analysis therefore suggests that healthcare demand can only be kept within manageable levels through the rapid adoption of public health measures (including testing and isolation of cases and wider social distancing measures) to suppress transmission, similar to those being adopted in many countries at the current time. If a suppression strategy is implemented early (at 0.2 deaths per 100,000 population per week) and sustained, then 38.7 million lives could be saved whilst if it is initiated when death numbers are higher (1.6 deaths per 100,000 population per week) then 30.7 million lives could be saved. Delays in implementing strategies to suppress transmission will lead to worse outcomes and fewer lives saved. We do not consider the wider social and economic costs of suppression, which will be high and may be disproportionately so in lower income settings. Moreover, suppression strategies will need to be maintained in some manner until vaccines or effective treatments become available to avoid the risk of later epidemics. Our analysis highlights the challenging decisions faced by all governments in the coming weeks and months, but demonstrates the extent to which rapid, decisive and collective action now could save millions of lives.