Publications
70 results found
Flaxman S, Kasonka L, Cluver L, et al., 2023, List child dependents on death certificates., Science, Vol: 380
Lison A, Banholzer N, Sharma M, et al., 2023, Effectiveness assessment of non-pharmaceutical interventions: lessons learned from the COVID-19 pandemic, The Lancet Public Health, Vol: 8, Pages: e311-e317, ISSN: 2468-2667
Numerous studies have assessed the effectiveness of non-pharmaceutical interventions (NPIs), such as school closures and stay-at-home orders, during the COVID-19 pandemic. Such assessments can inform public health policy and contribute to evidence-based choices of NPIs during subsequentwaves or future epidemics. However, methodological issues and a lack of common standards have limited the practical value of the existing evidence. Based on our work and literature review, we discuss lessons learned from the COVID-19 pandemic and make recommendations for standardizing and improving assessment, data collection, and modeling. These recommendations can contribute to more reliable and policy-relevant assessments of NPI effectiveness during future epidemics.
Unwin H, Sherrard-Smith E, Churcher T, et al., 2023, Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria, Nature Communications, Vol: 14, Pages: 1-12, ISSN: 2041-1723
Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance.
Flaxman S, Whittaker C, Semenova E, et al., 2023, Assessment of COVID-19 as the underlying cause of death among children and young people aged 0 to 19 years in the US., Jama Network Open, Vol: 6, Pages: 1-9, ISSN: 2574-3805
IMPORTANCE: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. OBJECTIVE: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. DESIGN, SETTING, AND PARTICIPANTS: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. MAIN OUTCOMES AND MEASURES: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). RESULTS: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US
Unwin H, Cori A, Imai N, et al., 2022, Using next generation matrices to estimate the proportion of infections that are not detected in an outbreak, Epidemics: the journal of infectious disease dynamics, Vol: 41, ISSN: 1755-4365
Contact tracing, where exposed individuals are followed up to break ongoing transmission chains, is a key pillar of outbreak response for infectious disease outbreaks. Unfortunately, these systems are not fully effective, and infections can still go undetected as people may not remember all their contacts or contacts may not be traced successfully. A large proportion of undetected infections suggests poor contact tracing and surveillance systems, which could be a potential area of improvement for a disease response. In this paper, we present a method for estimating the proportion of infections that are not detected during an outbreak. Our method uses next generation matrices that are parameterized by linked contact tracing data and case line-lists. We validate the method using simulated data from an individual-based model and then investigate two case studies: the proportion of undetected infections in the SARS-CoV-2 outbreak in New Zealand during 2020 and the Ebola epidemic in Guinea during 2014. We estimate that only 5.26% of SARS-CoV-2 infections were not detected in New Zealand during 2020 (95% credible interval: 0.243 – 16.0%) if 80% of contacts were under active surveillance but depending on assumptions about the ratio of contacts not under active surveillance versus contacts under active surveillance 39.0% or 37.7% of Ebola infections were not detected in Guinea (95% credible intervals: 1.69 – 87.0% or 1.70 – 80.9%).
Hillis S, N'konzi J-P, Msemburi W, et al., 2022, Orphanhood and caregiver loss among children based on new global excess COVID-19 death estimates, JAMA Pediatrics, Vol: 176, Pages: 1145-1148, ISSN: 1072-4710
The availability of new excess mortality data enables us to update global minimum estimates of COVID-19 orphanhood and caregiver death among children.1-4 Consequences for children can be devastating, including institutionalization, abuse, traumatic grief, mental health problems, adolescent pregnancy, poor educational outcomes, and chronic and infectious diseases.4,5 Global totals and country comparisons were previously hampered by inconsistencies in COVID-19 testing and incomplete death reporting. The new orphanhood estimates derived here based on excess deaths provide a comprehensive measure of COVID-19’s long-term impact on orphanhood and caregiver loss.
Flaxman S, Whittaker C, Semenova E, et al., 2022, Covid-19 is a leading cause of death in children and young people ages 0-19 years in the United States
<jats:title>Abstract</jats:title><jats:p>Covid-19 has caused more than 1 million deaths in the US, including at least 1,204 deaths among children and young people (CYP) aged 0-19 years, with 796 occurring in the one year period April 1, 2021 - March 31, 2022. Deaths among US CYP are rare in general, and so we argue here that the mortality burden of Covid-19 in CYP is best understood in the context of all other causes of CYP death. Using publicly available data from CDC WONDER on NCHS’s 113 Selected Causes of Death, and comparing to mortality in 2019, the immediate pre-pandemic period, we find that Covid-19 mortality is among the 10 leading causes of death in CYP aged 0-19 years in the US, ranking 8th among all causes of deaths, 5th in disease-related causes of deaths (excluding accidents, assault and suicide), and 1st in deaths caused by infectious or respiratory diseases. Covid-19 deaths constitute 2.3% of the 10 leading causes of death in this age group. Covid-19 caused substantially more deaths in CYP than major vaccine-preventable diseases did historically in the period before vaccines became available. Various factors including underreporting and Covid-19’s role as a contributing cause of death from other diseases mean that our estimates may understate the true mortality burden of Covid-19. Our findings underscore the public health relevance of Covid-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, pharmaceutical and non-pharmaceutical interventions will continue to play an important role in limiting transmission of the virus in CYP and mitigating severe disease.</jats:p>
Imai N, Gaythorpe K, Bhatia S, et al., 2022, COVID-19 in Japan, January – March 2020: insights from the first three months of the epidemic, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
Background:Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. Methods:We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. Results:The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period (16 – 23 March 2020), Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age with individuals more likely to infect, and be infected by, contacts in a similar age group to them. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.Conclusions:Information collected in the early phases of an out
Okell L, Brazeau NF, Verity R, et al., 2022, Estimating the COVID-19 infection fatality ratio accounting for seroreversion using statistical modelling, Communications Medicine, Vol: 2, Pages: 1-13, ISSN: 2730-664X
Background: The infection fatality ratio (IFR) is a key statistic for estimating the burden of coronavirus disease 2019 (COVID-19) and has been continuously debated throughout the COVID-19 pandemic. The age-specific IFR can be quantified using antibody surveys to estimate total infections, but requires consideration of delay-distributions from time from infection to seroconversion, time to death, and time to seroreversion (i.e. antibody waning) alongside serologic test sensitivity and specificity. Previous IFR estimates have not fully propagated uncertainty or accounted for these potential biases, particularly seroreversion. Methods: We built a Bayesian statistical model that incorporates these factors and applied this model to simulated data and 10 serologic studies from different countries. Results: We demonstrate that seroreversion becomes a crucial factor as time accrues but is less important during first-wave, short-term dynamics. We additionally show that disaggregating surveys by regions with higher versus lower disease burden can inform serologic test specificity estimates. The overall IFR in each setting was estimated at 0.49 -2.53%.Conclusion: We developed a robust statistical framework to account for full uncertainties in the parameters determining IFR. We provide code for others to apply these methods to further datasets and future epidemics.
Hillis S, Ntwali Nkonzi J-P, Msemburi W, et al., 2022, 10.4 Million Children Affected by COVID-19-associated Orphanhood and Caregiver Death: An Imperative for Action
<jats:title>Abstract</jats:title><jats:p>The new WHO estimates for COVID-19 excess deaths allow us to generate supdated and more accurate models of COVID-19 associated orphanhood and caregiver loss. Using methodology established in prior studies, we combine age-specific fertility and excess death estimates from January 2020 to May 2022. We find 10.4 million children have lost a parent or caregiver due to COVID-associated excess deaths, and 7.5 million children have experienced COVID-associated orphanhood. Without supportive intervention, caregiver loss can bring severe risks of poverty, school dropout, sexual exploitation, and mental health distress. It is essential that evidence-based care for these children is integrated into all national response plans as a caring action to protect children from immediate and long-term harms of COVID-19.</jats:p>
Unwin HJT, Hillis S, Cluver L, et al., 2022, Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study, The Lancet Child & Adolescent Health, Vol: 6, Pages: 249-259, ISSN: 2352-4642
BACKGROUND: In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, we aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). METHODS: We used updated excess mortality and fertility data to model increases in minimum estimates of COVID-19-associated orphanhood and caregiver deaths from our original study period of March 1, 2020-April 30, 2021, to include the new period of May 1-Oct 31, 2021, for 21 countries. Orphanhood was defined as the death of one or both parents; primary caregiver loss included parental death or the death of one or both custodial grandparents; and secondary caregiver loss included co-residing grandparents or kin. We used logistic regression and further incorporated a fixed effect for western European countries into our previous model to avoid over-predicting caregiver loss in that region. For the entire 20-month period, we grouped children by age (0-4 years, 5-9 years, and 10-17 years) and maternal or paternal orphanhood, using fertility contributions, and we modelled global and regional extrapolations of numbers of orphans. 95% credible intervals (CrIs) are given for all estimates. FINDINGS: The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7-90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100-2 987 000) to 5 200 300 (3 619 400-5 731 400). Between March 1, 2020, and Oct 31, 2021, 491 300 (95% CrI 485 100-497 900) children
Imai N, Gaythorpe KAM, Bhatia S, et al., 2022, COVID-19 in Japan: insights from the first three months of the epidemic, Publisher: Cold Spring Harbor Laboratory
BackgroundUnderstanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. MethodsWe conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. ResultsThe corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period, Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.ConclusionsInformation collected in the early phases of an outbreak are important in characterising any novel pathogen. Timely recognition of key symptoms and high-risk settings for transmi
Pan Y, Zhang L, Unwin H, et al., 2022, Discovering spatial-temporal patterns via complex networks in investigating COVID-19 pandemic in the United States, Sustainable Cities and Society, Vol: 77, Pages: 1-19, ISSN: 2210-6707
A novel approach combining time series analysis and complex network theory is proposed to deeply explore characteristics of the COVID-19 pandemic in some parts of the United States (US). It merges as a new way to provide a systematic view and complementary information of COVID-19 progression in the US, enabling evidence-based responses towards pandemic intervention and prevention. To begin with, the Principal Component Analysis (PCA) varimax is adopted to fuse observed time-series data about the pandemic evolution in each state across the US. Then, relationships between the pandemic progress of two individual states are measured by different synchrony metrics, which can then be mapped into networks under unique topological characteristics. Lastly, the hidden knowledge in the established networks can be revealed from different perspectives by network structure measurement, community detection, and online random forest, which helps to inform data-driven decisions for battling the pandemic. It has been found that states gathered in the same community by diffusion entropy reducer (DER) are prone to be geographically close and share a similar pattern and tendency of COVID-19 evolution. Social factors regarding the political party, Gross Domestic Product (GDP), and population density are possible to be significantly associated with the two detected communities within a constructed network. Moreover, the cluster-specific predictor based on online random forest and sliding window is proven useful in dynamically capturing and predicting the epidemiological trends for each community, which can reach the highest R square of 0.887.
Unwin HJT, Smith ES, Churcher TS, et al., 2022, Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria
<jats:title>Abstract</jats:title><jats:p>Long lasting insecticide treated mosquito nets (LLINs) provide both direct and indirect protection against bites from mosquitoes potentially transmitting malaria. Direct personal protection is provided to net users given both the net’s physical barrier and its insecticidal action. Indirect mass protection for the community is afforded through reduced infectious bites per person annually (entomological inoculation rate, EIR). Quantifying these protective effects can help strategize options for net interventions, particularly as insecticide-resistant mosquitoes spread.</jats:p><jats:p>These types of protection are inherently linked, rendering it impossible to empirically quantify the contribution of each to the overall ‘community effect’, instead we investigate this with a modelling framework and compare model predictions to trends with Demographic Health Survey (DHS) data.</jats:p><jats:p>Our modelling exercise predicts that in a situation with an EIR of 100, the reduction in EIR from an untreated net used by 80% of the population is 52% [95% CI: 12% - 84%] for users and 21% [95% CI: 0% - 57%] for non-users. Due to the impact of the insecticide, the reduction in EIR for LLINs is 89% [95% CI: 67% - 98%] for users and 74% [95% CI: 48% - 92%] for non-users, but this protection reduces as insecticide resistance in mosquitoes increases. Modelled trends in the difference in protection between users and non-users across endemicity and net usage levels are consistent with DHS data (2000-2018).</jats:p><jats:p>This study supports the concept of a community effect from LLINs, highlights the value of blocking and killing mosquitoes for community protection. Achieving high LLIN usage is always preferential, but there remains protection to non-users as the number of people using nets increases.</jats:p>
Hillis S, Blenkinsop A, Villaveces A, et al., 2021, COVID-19-associated orphanhood and caregiver death in the United States, Pediatrics, Vol: 148, Pages: 1-13, ISSN: 0031-4005
Background: Most COVID-19 deaths occur among adults, not children, and attention has focused on mitigating COVID-19 burden among adults. However, a tragic consequence of adult deaths is that high numbers of children might lose their parents and caregivers to COVID-19-associated deaths.Methods: We quantified COVID-19-associated caregiver loss and orphanhood in the US and for each state using fertility and excess and COVID-19 mortality data. We assessed burden and rates of COVID-19-associated orphanhood and deaths of custodial and co-residing grandparents, overall and by race/ethnicity. We further examined variations in COVID-19-associated orphanhood by race/ethnicity for each state. Results: We found that from April 1, 2020 through June 30, 2021, over 140,000 children in the US experienced the death of a parent or grandparent caregiver. The risk of such loss was 1.1 to 4.5 times higher among children of racial and ethnic minorities, compared to Non-Hispanic White children. The highest burden of COVID-19-associated death of parents and caregivers occurred in Southern border states for Hispanic children, Southeastern states for Black children, and in states with tribal areas for American Indian/Alaska Native populations.Conclusions: We found substantial disparities in distributions of COVID-19-associated death of parents and caregivers across racial and ethnic groups. Children losing caregivers to COVID-19 need care and safe, stable, and nurturing families with economic support, quality childcare and evidence-based parenting support programs. There is an urgent need to mount an evidence-based comprehensive response focused on those children at greatest risk, in the states most affected.
Unwin H, Mwandigha L, Winskill P, et al., 2021, Analysis of the potential for a malaria vaccine to reduce gaps in malaria intervention coverage, Malaria Journal, Vol: 20, Pages: 1-11, ISSN: 1475-2875
BackgroundThe RTS,S/AS01 malaria vaccine is currently being evaluated in a cluster-randomized pilot implementation programme in three African countries. This study seeks to identify whether vaccination could reach additional children who are at risk from malaria but do not currently have access to, or use, core malaria interventions.MethodsUsing data from household surveys, the overlap between malaria intervention coverage and childhood vaccination (diphtheria-tetanus-pertussis dose 3, DTP3) uptake in 20 African countries with at least one first administrative level unit with Plasmodium falciparum parasite prevalence greater than 10% was calculated. Multilevel logistic regression was used to explore patterns of overlap by demographic and socioeconomic variables. The public health impact of delivering RTS,S/AS01 to those children who do not use an insecticide-treated net (ITN), but who received the DTP3 vaccine, was also estimated.ResultsUptake of DTP3 was higher than malaria intervention coverage in most countries. Overall, 34% of children did not use ITNs and received DTP3, while 35% of children used ITNs and received DTP3, although this breakdown varied by country. It was estimated that there are 33 million children in these 20 countries who do not use an ITN. Of these, 23 million (70%) received the DTP3 vaccine. Vaccinating those 23 million children who receive DTP3 but do not use an ITN could avert up to an estimated 9.7 million (range 8.5–10.8 million) clinical malaria cases each year, assuming all children who receive DTP3 are administered all four RTS,S doses. An additional 10.8 million (9.5–12.0 million) cases could be averted by vaccinating those 24 million children who receive the DTP3 vaccine and use an ITN. Children who had access to or used an ITN were 9–13% more likely to reside in rural areas compared to those who had neither intervention regardless of vaccination status. Mothers’ education status was a strong predictor of inte
Bhatia S, Parag K, Wardle J, et al., 2021, Global predictions of short- to medium-term COVID-19 transmission trends : a retrospective assessment
<jats:title>Abstract</jats:title> <jats:p>From 8th March to 29th November 2020, we produced weekly estimates of SARS-CoV-2 transmissibility and forecasts of deaths due to COVID-19 for 81 countries with evidence of sustained transmission. We also developed a novel heuristic to combine weekly estimates of transmissibility to produce forecasts over a 4-week horizon. We evaluated the robustness of the forecasts using relative error, coverage probability, and comparisons with null models. During the 39-week period covered by this study, both the short- and medium-term forecasts captured well the epidemic trajectory across different waves of COVID-19 infections with small relative errors over the forecast horizon. The model was well calibrated with 56.3\% and 45.6\% of the observations lying in the 50\% Credible Interval in 1-week and 4-week ahead forecasts respectively. We could accurately characterise the overall phase of the epidemic up to 4-weeks ahead in 84.9\% of country-days. The medium-term forecasts can be used in conjunction with the short-term forecasts of COVID-19 mortality as a useful planning tool as countries continue to relax public health measures.</jats:p>
Dorigatti I, Lavezzo E, Manuto L, et al., 2021, SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo' (vol 12, 4383, 2021), Nature Communications, Vol: 12, Pages: 1-1, ISSN: 2041-1723
Mishra S, Scott JA, Laydon DJ, et al., 2021, Comparing the responses of the UK, Sweden and Denmark to COVID-19 using counterfactual modelling, SCIENTIFIC REPORTS, Vol: 11, Pages: 1-9, ISSN: 2045-2322
The UK and Sweden have among the worst per-capita COVID-19 mortality in Europe. Sweden stands out for its greater reliance on voluntary, rather than mandatory, control measures. We explore how the timing and effectiveness of control measures in the UK, Sweden and Denmark shaped COVID-19 mortality in each country, using a counterfactual assessment: what would the impact have been, had each country adopted the others’ policies? Using a Bayesian semi-mechanistic model without prior assumptions on the mechanism or effectiveness of interventions, we estimate the time-varying reproduction number for the UK, Sweden and Denmark from daily mortality data. We use two approaches to evaluate counterfactuals which transpose the transmission profile from one country onto another, in each country’s first wave from 13th March (when stringent interventions began) until 1st July 2020. UK mortality would have approximately doubled had Swedish policy been adopted, while Swedish mortality would have more than halved had Sweden adopted UK or Danish strategies. Danish policies were most effective, although differences between the UK and Denmark were significant for one counterfactual approach only. Our analysis shows that small changes in the timing or effectiveness of interventions have disproportionately large effects on total mortality within a rapidly growing epidemic.
Olney A, Smith J, Sen S, et al., 2021, Estimating the effect of social distancing Interventions on COVID-19 in the United States, American Journal of Epidemiology, Vol: 190, Pages: 1504-1509, ISSN: 0002-9262
Since its global emergence in 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused multiple epidemics in the United States. When medical treatments for the virus were still emerging and a vaccine was not yet available, state and local governments sought to limit its spread by enacting various social-distancing interventions, such as school closures and lockdowns; however, the effectiveness of these interventions was unknown. We applied an established, semimechanistic Bayesian hierarchical model of these interventions to the spread of SARS-CoV-2 from Europe to the United States, using case fatalities from February 29, 2020, up to April 25, 2020, when some states began reversing their interventions. We estimated the effects of interventions across all states, contrasted the estimated reproduction numbers before and after lockdown for each state, and contrasted the predicted number of future fatalities with the actual number of fatalities as a check of the model’s validity. Overall, school closures and lockdowns were the only interventions modeled that had a reliable impact on the time-varying reproduction number, and lockdown appears to have played a key role in reducing that number to below 1.0. We conclude that reversal of lockdown without implementation of additional, equally effective interventions will enable continued, sustained transmission of SARS-CoV-2 in the United States.
Hillis S, Unwin H, Chen Y, et al., 2021, Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study, The Lancet, Vol: 398, Pages: 391-402, ISSN: 0140-6736
Background: The COVID-19 pandemic response has focused on prevention, detection, and response. Beyond morbidity and mortality, pandemics carry secondary impacts, such as children orphaned or bereft of their caregivers. Such children often face adverse consequences, including poverty, abuse, and institutionalization. We provide estimates for the magnitude of this problem resulting from COVID-19 and describe the need for resource allocation.Methods: We use mortality and fertility data to model minimum estimates and rates of COVID-19-associated orphanhood (death of 1 or both parents) and deaths of custodial and co-residing grandparents for 21 countries. We use these estimates to model global extrapolations for the number of children experiencing COVID-19-associated deaths of parents and grandparents ages 60-84.Results: Globally, from March 1, 2020-March 31, 2021, we estimate 974,000 children experienced death of primary caregivers, including parents or custodial grandparents; >1.3 million experienced death of primary caregivers and co-residing grandparents (or kin). Countries with rates of primary caregiver deaths >1/1000 children included Peru, South Africa, Mexico, Colombia, Brazil, I.R. Iran, U.S.A., and Russia (range, 1.0-8.5/1000). Numbers of children orphaned exceeded numbers of deaths among those aged 15 – 44; 2 – 5 times more children had deceased fathers than deceased mothers. Conclusions: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families nurture children bereft of caregivers and help ensure institutionalization is avoided. These data demonstrate the need for an additional pillar of our response: prevent, detect, respond, and care for children.
Mishra S, Mindermann S, Sharma M, et al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England, EClinicalMedicine, Vol: 39, Pages: 1-8, ISSN: 2589-5370
BackgroundSince its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital.MethodsWe examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021.FindingsAcross data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May.InterpretationThe outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control effortsFundingNational Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy
Dorigatti I, Lavezzo E, Manuto L, et al., 2021, SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’, Nature Communications, Vol: 12, Pages: 1-11, ISSN: 2041-1723
In February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8%-4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7%-100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95%CI:11.0%-28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95%CrI:17.2%-36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.
Routledge I, Unwin HJT, Bhatt S, 2021, Inference of malaria reproduction numbers in three elimination settings by combining temporal data and distance metrics, Scientific Reports, Vol: 11, ISSN: 2045-2322
Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers. We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time. Model comparison suggested that including spatial information improved models as measured by second order AIC (ΔAICc), compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (> 200 km) was possible. Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacenc
Gaythorpe K, Bhatia S, Mangal T, et al., 2021, Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility, Scientific Reports, Vol: 11, Pages: 1-14, ISSN: 2045-2322
Background: SARS-CoV-2 infections have been reported in all age groups including infants, children, and adolescents. However, the role of children in the COVID-19 pandemic is still uncertain. This systematic review of early studies synthesises evidence on the susceptibility of children to SARS-CoV-2 infection, the severity and clinical outcomes in children with SARS-CoV-2 infection, and the transmissibility of SARS-CoV-2 by children in the early phases of the COVID-19 pandemic. Methods and findings: A systematic literature review was conducted in PubMed. Reviewers extracted data from relevant, peer-reviewed studies published up to July 4th 2020 during the first wave of the SARS-CoV-2 outbreak using a standardised form and assessed quality using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. For studies included in the meta-analysis, we used a random effects model to calculate pooled estimates of the proportion of children considered asymptomatic or in a severe or critical state. We identified 2,775 potential studies of which 128 studies met our inclusion criteria; data were extracted from 99, which were then quality assessed. Finally, 29 studies were considered for the meta-analysis that included information of symptoms and/or severity, these were further assessed based on patient recruitment. Our pooled estimate of the proportion of test positive children who were asymptomatic was 21.1% (95% CI: 14.0 - 28.1%), based on 13 included studies, and the proportion of children with severe or critical symptoms was 3.8% (95% CI: 1.5 - 6.0%), based on 14 included studies. We did not identify any studies designed to assess transmissibility in children and found that susceptibility to infection in children was highly variable across studies.Conclusions: Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varied widely between studies. However, it is evident that most children e
Smith TP, Flaxman S, Gallinat AS, et al., 2021, Temperature and population density influence SARS-CoV-2 transmission in the absence of nonpharmaceutical interventions, Proceedings of the National Academy of Sciences of USA, Vol: 118, Pages: 1-8, ISSN: 0027-8424
As COVID-19 continues to spread across the world, it is increasingly important to understand the factors that influence its transmission. Seasonal variation driven by responses to changing environment has been shown to affect the transmission intensity of several coronaviruses. However, the impact of the environment on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains largely unknown, and thus seasonal variation remains a source of uncertainty in forecasts of SARS-CoV-2 transmission. Here we address this issue by assessing the association of temperature, humidity, ultraviolet radiation, and population density with estimates of transmission rate (R). Using data from the United States, we explore correlates of transmission across US states using comparative regression and integrative epidemiological modeling. We find that policy intervention (“lockdown”) and reductions in individuals’ mobility are the major predictors of SARS-CoV-2 transmission rates, but, in their absence, lower temperatures and higher population densities are correlated with increased SARS-CoV-2 transmission. Our results show that summer weather cannot be considered a substitute for mitigation policies, but that lower autumn and winter temperatures may lead to an increase in transmission intensity in the absence of policy interventions or behavioral changes. We outline how this information may improve the forecasting of COVID-19, reveal its future seasonal dynamics, and inform intervention policies.
Mishra S, Mindermann S, Sharma M, et al., 2021, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Publisher: Imperial College London, 44
Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when, whether, and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. This is particularly true for England, which has high coverage from vaccines that are likely more protective against B.1.1.7 than some other VOCs. We examine trends in B.1.1.7’s prevalence in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. Our results suggest shifts in the composition of SARS-CoV-2 lineages driving transmission in England between March and April 2021. Local transmission of non-B.1.1.7 VOCs may be increasing; this warrants urgent further investigation.
Mishra S, Mindermann S, Sharma M, et al., 2021, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Report 44: Recent trends in SARS-CoV-2 variants of concern in England, Publisher: Imperial College London, 44
Since its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when, whether, and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital. This is particularly true for England, which has high coverage from vaccines that are likely more protective against B.1.1.7 than some other VOCs. We examine trends in B.1.1.7’s prevalence in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. Our results suggest shifts in the composition of SARS-CoV-2 lineages driving transmission in England between March and April 2021. Local transmission of non-B.1.1.7 VOCs may be increasing; this warrants urgent further investigation.
Dorigatti I, Lavezzo E, Manuto L, et al., 2021, SARS-CoV-2 antibody dynamics, within-household transmission and the impact of contact tracing from community-wide serological testing in the Italian Municipality of Vo’, Publisher: Elsevier BV
Background: In February and Mach 2020, two mass swab testing campaigns conducted in Vo’, Italy demonstrated the extent of asymptomatic SARS-CoV-2 infection and the feasibility of epidemic suppression.Methods: We tested 86% of the Vo’ population (2,602 subjects) in May with three immuno-assays detecting antibodies against the spike (S) and nucleocapsid (N) antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November.Findings: Combining the results obtained with the three assays, we estimate a seroprevalence of 3.5% (95% Credible Interval (CrI) 2.8%-4.3%) in May. In November, all assays showed a reduction in antibody titres, though 98.8% (95% Confidence Interval (CI) 93.7%-100.0%) of sera still reacted against at least one antigen. Conversely, 18.6% (95% CI 11.0%-28.5%) showed a marked increase of antibody or viral neutralisation reactivity between May and November, linked to documented or likely re-exposures. We found significant differences in the magnitude and persistence of the antibody response by age group but not by symptom occurrence, hospitalisation, or sex. Analysis of the serostatus of 1,118 households indicated a 27.3% (95% CrI 19.2%-34.6%) probability of SARS-CoV-2 transmission among household members and that 81.8% (95% CrI 55.9%-95.2%) of transmission could be attributed to 20% of infections. Contact tracing correctly identified 44% of the infected subjects and had limited impact on the epidemic.Interpretation: We find evidence of antibody persistence up to nine months post infection. Different assays provided significantly different seroprevalence estimates, making it challenging to compare seroprevalence estimates globally. Due to the high population susceptibility and the limited impact of contact tracing, rigorous testing and improvements in contact tracing are essential to control SARS-CoV-2.Funding: Veneto Region, Med
Watson O, Alhaffar M, Mehchy Z, et al., 2021, Leveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723
The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% – 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 – 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% – 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.
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