Imperial College London

ProfessorSamirBhatt

Faculty of MedicineSchool of Public Health

Professor of Statistics and Public Health
 
 
 
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Contact

 

+44 (0)20 7594 5029s.bhatt

 
 
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Location

 

G32ASt Mary's Research BuildingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

167 results found

Mlcochova P, Kemp S, Dhar MS, Papa G, Meng B, Ferreira IATM, Datir R, Collier DA, Albecka A, Singh S, Pandey R, Brown J, Zhou J, Goonawardane N, Mishra S, Whittaker C, Mellan T, Marwal R, Datta M, Sengupta S, Ponnusamy K, Radhakrishnan VS, Abdullahi A, Charles O, Chattopadhyay P, Devi P, Caputo D, Peacock T, Wattal DC, Goel N, Satwik A, Vaishya R, Agarwal M, Indian SARS-CoV-2 Genomics Consortium INSACOG, Genotype to Phenotype Japan G2P-Japan Consortium, CITIID-NIHR BioResource COVID-19 Collaboration, Mavousian A, Lee JH, Bassi J, Silacci-Fegni C, Saliba C, Pinto D, Irie T, Yoshida I, Hamilton WL, Sato K, Bhatt S, Flaxman S, James LC, Corti D, Piccoli L, Barclay WS, Rakshit P, Agrawal A, Gupta RKet al., 2021, SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion., Nature

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7, associated with B.1.617.2 spike in a predominantly cleaved state compared to B.1.1.7. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralising antibody as compared to WT spike. Additionally we observed that B.1.617.2 had higher replication and spike mediated entry as compared to B.1.617.1, potentially explaining B.1.617.2 dominance. In an analysis of over 130 SARS-CoV-2 infected healthcare workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx-1 vaccine effectiveness against B.1.617.2 relative to non- B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan TA, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason GP, Ratmann O, Semenova E, Leech G, Sandkühler JF, Rogers-Smith C, Vollmer M, Unwin HJT, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson NM, Bhatt S, Brauner JM, Flaxman S, COVID-19 Genomics UK COG-UK Consortiumet al., 2021, Changing composition of SARS-CoV-2 lineages and rise of Delta variant in England., EClinicalMedicine, Vol: 39

Background: Since 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. Methods: We 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. Findings: Across 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. Interpretation: The 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 efforts. Funding: National Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open

Journal article

Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJet al., 2021, The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study., BMC Medicine, Vol: 19, Pages: 1-12, ISSN: 1741-7015

BACKGROUND: The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain. METHODS: A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease). RESULTS: One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)]. CONCLUSION: Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU

Journal article

Brito AF, Semenova E, Dudas G, Hassler GW, Kalinich CC, Kraemer MUG, Hill SC, Danish Covid-19 Genome Consortium, Sabino EC, Pybus OG, Dye C, Bhatt S, Flaxamn S, Suchard MA, Grubaugh ND, Baele G, Faria NRet al., 2021, Global disparities in SARS-CoV-2 genomic surveillance., medRxiv

The COVID-19 pandemic has revealed the importance of virus genome sequencing to guide public health interventions to control virus transmission and understand SARS-CoV-2 evolution. As of July 20th, 2021, >2 million SARS-CoV-2 genomes have been submitted to GISAID, 94% from high income and 6% from low and middle income countries. Here, we analyse the spatial and temporal heterogeneity in SARS-CoV-2 global genomic surveillance efforts. We report a comprehensive analysis of virus lineage diversity and genomic surveillance strategies adopted globally, and investigate their impact on the detection of known SARS-CoV-2 virus lineages and variants of concern. Our study provides a perspective on the global disparities surrounding SARS-CoV-2 genomic surveillance, their causes and consequences, and possible solutions to maximize the impact of pathogen genome sequencing for efforts on public health. One-Sentence Summary: The causes, consequences and possible solutions for disparities in genomic surveillance observed in the COVID-19 pandemic.

Journal article

Bhatt S, 2021, Understanding the effectiveness of government interventions against the resurgence of COVID-19 in Europe, Nature Communications, ISSN: 2041-1723

As European governments face resurging waves of COVID-19, non-pharmaceutical interventions (NPIs) continue to be the primary tool for infection control. However, updated estimates of their relative effectiveness have been absent for Europe’s second wave, largely due to a lack of collated data that considers the increased subnational variation and diversity of NPIs. We collect the largest dataset of NPI implementation dates in Europe, spanning 114 subnational areas in 7 countries, with a systematic categorisation of interventions tailored to the second wave. Using a hierarchical Bayesian transmission model, we estimate the effectiveness of 17 NPIs from local case and death data. We manually validate the data, address limitations in modelling from previous studies, and extensively test the robustness of our estimates. The combined effect of all NPIs was smaller relative to estimates from the first half of 2020, indicating the strong influence of safety measures and individual protective behaviours--such as distancing--that persisted after the first wave. Closing specific businesses was highly effective. Gathering restrictions were highly effective but only for the strictest limits. We find smaller effects for closing educational institutions compared to the first wave, suggesting that safer operation of schools was possible with a set of stringent safety measures including testing and tracing, preventing mixing, and smaller classes. These results underscore that effectiveness estimates from the early stage of an epidemic are measured relative to pre-pandemic behaviour. Updated estimates are required to inform policy in an ongoing pandemic.

Journal article

Ratmann O, Bhatt S, Flaxman S, 2021, Implications of a highly transmissible variant of SARS-CoV-2 for children, Archives of Disease in Childhood, Vol: 106, Pages: 1-1, ISSN: 0003-9888

Journal article

Mishra S, Scott JA, Laydon DJ, Flaxman S, Gandy A, Mellan TA, Unwin HJT, Vollmer M, Coupland H, Ratmann O, Monod M, Zhu HH, Cori A, Gaythorpe KAM, Whittles LK, Whittaker C, Donnelly CA, Ferguson NM, Bhatt Set 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.

Journal article

Hillis S, Unwin H, Chen Y, Cluver L, Sherr L, Goldman P, Ratmann O, Donnelly C, Bhatt S, Villaveces A, Butchart A, Bachman G, Rawlings L, Green P, Nelson C, Flaxman Set 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.

Journal article

Meyerowitz-Katz G, Bhatt S, Ratmann O, Brauner JM, Flaxman S, Mishra S, Sharma M, Mindermann S, Bradley V, Vollmer M, Merone L, Yamey Get al., 2021, Is the cure really worse than the disease? The health impacts of lockdowns during COVID-19, BMJ Global Health, Vol: 6, Pages: 1-6, ISSN: 2059-7908

Journal article

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

Journal article

Krawczyk K, Chelkowski T, Laydon DJ, Mishra S, Xifara D, Gibert B, Flaxman S, Mellan T, Schwämmle V, Röttger R, Hadsund JT, Bhatt Set al., 2021, Correction: Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource., J Med Internet Res, Vol: 23

[This corrects the article DOI: 10.2196/28253.].

Journal article

Bertozzi-Villa A, Bever CA, Koenker H, Weiss DJ, Vargas-Ruiz C, Nandi AK, Gibson HS, Harris J, Battle KE, Rumisha SF, Keddie S, Amratia P, Arambepola R, Cameron E, Chestnutt EG, Collins EL, Millar J, Mishra S, Rozier J, Symons T, Twohig KA, Hollingsworth TD, Gething PW, Bhatt Set al., 2021, Maps and metrics of insecticide-treated net access, use, and nets-per-capita in Africa from 2000-2020, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723

Journal article

Krawczyk K, Chelkowski T, Laydon DJ, Mishra S, Xifara D, Flaxman S, Mellan T, Schwammle V, Rottger R, Hadsund JT, Bhatt Set al., 2021, Quantifying Online News Media Coverage of the COVID-19 Pandemic: Text Mining Study and Resource, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 23, ISSN: 1438-8871

Journal article

Faria NR, Mellan TA, Whittaker C, Claro IM, Candido DDS, Mishra S, Crispim MAE, Sales FC, Hawryluk I, McCrone JT, Hulswit RJG, Franco LAM, Ramundo MS, de Jesus JG, Andrade PS, Coletti TM, Ferreira GM, Silva CAM, Manuli ER, Pereira RHM, Peixoto PS, Kraemer MU, Gaburo N, Camilo CDC, Hoeltgebaum H, Souza WM, Rocha EC, de Souza LM, de Pinho MC, Araujo LJT, Malta FS, de Lima AB, Silva JDP, Zauli DAG, Ferreira ACDS, Schnekenberg RP, Laydon DJ, Walker PGT, Schlueter HM, dos Santos ALP, Vidal MS, Del Caro VS, Filho RMF, dos Santos HM, Aguiar RS, Proenca-Modena JLP, Nelson B, Hay JA, Monod M, Miscouridou X, Coupland H, Sonabend R, Vollmer M, Gandy A, Prete CA, Nascimento VH, Suchard MA, Bowden TA, Pond SLK, Wu C-H, Ratmann O, Ferguson NM, Dye C, Loman NJ, Lemey P, Rambaut A, Fraiji NA, Carvalho MDPSS, Pybus OG, Flaxman S, Bhatt S, Sabino ECet al., 2021, Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil, SCIENCE, Vol: 372, Pages: 815-+, ISSN: 0036-8075

Journal article

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan T, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason G, Ratmann O, Leech G, Fabienne Sandkühler J, Rogers-Smith C, Vollmer M, Unwin H, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson N, Bhatt S, Brauner J, Flaxman Set 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.

Report

Mishra S, Mindermann S, Sharma M, Whittaker C, Mellan T, Wilton T, Klapsa D, Mate R, Fritzsche M, Zambon M, Ahuja J, Howes A, Miscouridou X, Nason G, Ratmann O, Leech G, Fabienne Sandkühler J, Rogers-Smith C, Vollmer M, Unwin H, Gal Y, Chand M, Gandy A, Martin J, Volz E, Ferguson N, Bhatt S, Brauner J, Flaxman Set 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.

Report

Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, O'Toole Á, Amato R, Ragonnet-Cronin M, Harrison I, Jackson B, Ariani CV, Boyd O, Loman NJ, McCrone JT, Gonçalves S, Jorgensen D, Myers R, Hill V, Jackson DK, Gaythorpe K, Groves N, Sillitoe J, Kwiatkowski DP, COVID-19 Genomics UK COG-UK consortium, Flaxman S, Ratmann O, Bhatt S, Hopkins S, Gandy A, Rambaut A, Ferguson NMet al., 2021, Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England, Nature, Vol: 593, Pages: 266-269, ISSN: 0028-0836

The SARS-CoV-2 lineage B.1.1.7, designated a Variant of Concern 202012/01 (VOC) by Public Health England1, originated in the UK in late Summer to early Autumn 20202. Whole genome SARS-CoV-2 sequence data collected from community-based diagnostic testing shows an unprecedentedly rapid expansion of the B.1.1.7 lineage during Autumn 2020, suggesting a selective advantage. We find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Time-varying reproduction numbers for the VOC and cocirculating lineages were estimated using SGTF and genomic data. The best supported models did not indicate a substantial difference in VOC transmissibility among different age groups. There is a consensus among all analyses that the VOC has a substantial transmission advantage with a 50% to 100% higher reproduction number.

Journal article

Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati Met al., 2021, Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas, Remote Sensing of Environment: an interdisciplinary journal, Vol: 257, ISSN: 0034-4257

Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3 m × 3 m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.

Journal article

Laydon D, Mishra S, Hinsley W, Samartsidis P, Flaxman S, Gandy A, Ferguson N, Bhatt Set al., 2021, Modelling the impact of the Tier system on SARS-CoV-2 transmission in the UK between the first and second national lockdowns, BMJ Open, Vol: 11, ISSN: 2044-6055

Objective To measure the effects of the tier system on the COVID-19 pandemic in the UK between the first and second national lockdowns, before the emergence of the B.1.1.7 variant of concern.Design This is a modelling study combining estimates of real-time reproduction number Rt (derived from UK case, death and serological survey data) with publicly available data on regional non-pharmaceutical interventions. We fit a Bayesian hierarchical model with latent factors using these quantities to account for broader national trends in addition to subnational effects from tiers.Setting The UK at lower tier local authority (LTLA) level. 310 LTLAs were included in the analysis.Primary and secondary outcome measures Reduction in real-time reproduction number Rt.Results Nationally, transmission increased between July and late September, regional differences notwithstanding. Immediately prior to the introduction of the tier system, Rt averaged 1.3 (0.9–1.6) across LTLAs, but declined to an average of 1.1 (0.86–1.42) 2 weeks later. Decline in transmission was not solely attributable to tiers. Tier 1 had negligible effects. Tiers 2 and 3, respectively, reduced transmission by 6% (5%–7%) and 23% (21%–25%). 288 LTLAs (93%) would have begun to suppress their epidemics if every LTLA had gone into tier 3 by the second national lockdown, whereas only 90 (29%) did so in reality.Conclusions The relatively small effect sizes found in this analysis demonstrate that interventions at least as stringent as tier 3 are required to suppress transmission, especially considering more transmissible variants, at least until effective vaccination is widespread or much greater population immunity has amassed.

Journal article

Watson O, Alhaffar M, Mehchy Z, Whittaker C, Akil Z, Brazeau N, Cuomo-Dannenburg G, Hamlet A, Thompson H, Baguelin M, Fitzjohn R, Knock E, Lees J, Whittles L, Mellan T, Winskill P, COVID-19 Response Team IC, Howard N, Clapham H, Checchi F, Ferguson N, Ghani A, Walker P, Beals Eet 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.

Journal article

Unwin HJT, Routledge I, Flaxman S, Rizoiu M-A, Lai S, Cohen J, Weiss DJ, Mishra S, Bhatt Set al., 2021, Using Hawkes Processes to model imported and local malaria cases in near-elimination settings, PLOS COMPUTATIONAL BIOLOGY, Vol: 17, ISSN: 1553-734X

Journal article

Nouvellet P, Bhatia S, Cori A, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, Eales O, van Elsland S, NASCIMENTO F, Fitzjohn R, Gaythorpe K, Geidelberg L, green W, Hamlet A, Hauck K, Hinsley W, Imai N, Jeffrey, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Nedjati Gilani G, Parag K, Pons Salort M, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Watson O, Whittaker C, Whittles L, Xi X, Ferguson N, Donnelly Cet al., 2021, Reduction in mobility and COVID-19 transmission, Nature Communications, Vol: 12, ISSN: 2041-1723

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts.Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world.Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation.In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

Journal article

Vollmer MAC, Glampson B, Mellan TA, Mishra S, Mercuri L, Costello C, Klaber R, Cooke G, Flaxman S, Bhatt Set al., 2021, A unified machine learning approach to time series forecasting applied to demand at emergency departments, BMC Emergency Medicine, Vol: 21, Pages: 1-14, ISSN: 1471-227X

There were 25.6 million attendances at Emergency Departments (EDs) in Englandin 2019 corresponding to an increase of 12 million attendances over the pastten years. The steadily rising demand at EDs creates a constant challenge toprovide adequate quality of care while maintaining standards and productivity.Managing hospital demand effectively requires an adequate knowledge of thefuture rate of admission. Using 8 years of electronic admissions data from twomajor acute care hospitals in London, we develop a novel ensemble methodologythat combines the outcomes of the best performing time series and machinelearning approaches in order to make highly accurate forecasts of demand, 1, 3and 7 days in the future. Both hospitals face an average daily demand of 208and 106 attendances respectively and experience considerable volatility aroundthis mean. However, our approach is able to predict attendances at theseemergency departments one day in advance up to a mean absolute error of +/- 14and +/- 10 patients corresponding to a mean absolute percentage error of 6.8%and 8.6% respectively. Our analysis compares machine learning algorithms tomore traditional linear models. We find that linear models often outperformmachine learning methods and that the quality of our predictions for any of theforecasting horizons of 1, 3 or 7 days are comparable as measured in MAE. Inaddition to comparing and combining state-of-the-art forecasting methods topredict hospital demand, we consider two different hyperparameter tuningmethods, enabling a faster deployment of our models without compromisingperformance. We believe our framework can readily be used to forecast a widerange of policy relevant indicators.

Journal article

Weiss DJ, Bertozzi-Villa A, Rumisha SF, Amratia P, Arambepola R, Battle KE, Cameron E, Chestnutt E, Gibson HS, Harris J, Keddie S, Millar JJ, Rozier J, Symons TL, Vargas-Ruiz C, Hay SI, Smith DL, Alonso PL, Noor AM, Bhatt S, Gething PWet al., 2021, Indirect effects of the COVID-19 pandemic on malaria intervention coverage, morbidity, and mortality in Africa: a geospatial modelling analysis, LANCET INFECTIOUS DISEASES, Vol: 21, Pages: 59-69, ISSN: 1473-3099

Journal article

Fu H, Wang H, Xi X, Boonyasiri A, Wang Y, Hinsley W, Fraser KJ, McCabe R, Olivera Mesa D, Skarp J, Ledda A, Dewé T, Dighe A, Winskill P, van Elsland SL, Ainslie KEC, Baguelin M, Bhatt S, Boyd O, Brazeau NF, Cattarino L, Charles G, Coupland H, Cucunubá ZM, Cuomo-Dannenburg G, Donnelly CA, Dorigatti I, Eales OD, Fitzjohn RG, Flaxman S, Gaythorpe KAM, Ghani AC, Green WD, Hamlet A, Hauck K, Haw DJ, Jeffrey B, Laydon DJ, Lees JA, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag KV, Ragonnet-Cronin M, Riley S, Schmit N, Thompson HA, Unwin HJT, Verity R, Vollmer MAC, Volz E, Walker PGT, Walters CE, Waston OJ, Whittaker C, Whittles LK, Imai N, Bhatia S, Ferguson NMet al., 2021, A database for the epidemic trends and control measures during the first wave of COVID-19 in mainland China, International Journal of Infectious Diseases, Vol: 102, Pages: 463-471, ISSN: 1201-9712

Objectives: This data collation effort aims to provide a comprehensive database to describe the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19)across main provinces in China. Methods: From mid-January to March 2020, we extracted publicly available data on the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted a descriptive analysis of the epidemics in the six most-affected provinces. Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends were different across provinces. Compared to Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as local transmission of COVID-19 declined, switching the focus of measures to testing and quarantine of inbound travellers could help to sustain the control of the epidemic. Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database with these indicators and information on control measures provides useful source for exploring further research and policy planning for response to the COVID-19 epidemic.

Journal article

Flaxman S, Mishra S, Scott J, Ferguson N, Gandy A, Bhatt Set al., 2020, The effect of interventions on COVID-19 Reply, NATURE, Vol: 588, Pages: E29-E32, ISSN: 0028-0836

Journal article

Unwin H, Mishra S, Bradley V, Gandy A, Mellan T, Coupland H, Ish-Horowicz J, Vollmer M, Whittaker C, Filippi S, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Ainslie K, Baguelin M, Boonyasiri A, Brazeau N, Cattarino L, Cucunuba Z, Cuomo-Dannenburg G, Dorigatti I, Eales O, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Siveroni I, Thompson H, Walker P, Walters C, Watson O, Whittles L, Ghani A, Ferguson N, Riley S, Donnelly C, Bhatt S, Flaxman Set al., 2020, State-level tracking of COVID-19 in the United States, Nature Communications, Vol: 11, Pages: 1-9, ISSN: 2041-1723

As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly model the US epidemic at the state-level, using publicly available deathdata within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We use changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on therate of transmission of SARS-CoV-2. We estimate thatRtwas only below one in 23 states on 1st June. We also estimate that 3.7% [3.4%-4.0%] of the total population of the US had been infected, with wide variation between states, and approximately 0.01% of the population was infectious. We demonstrate good 3 week model forecasts of deaths with low error and good coverage of our credible intervals.

Journal article

Epstein A, Namuganga JF, Kamya EV, Nankabirwa J, Bhatt S, Rodriguez-Barraquer I, Staedke SG, Kamya MR, Dorsey G, Greenhouse Bet al., 2020, Estimating malaria incidence from routine health facility-based surveillance data in Uganda, MALARIA JOURNAL, Vol: 19

Journal article

Grassly NC, Pons-Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Teamet al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099

BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines

Journal article

Thompson H, Imai N, Dighe A, Ainslie K, Baguelin M, Bhatia S, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Cooper L, Coupland H, Cucunuba Z, Cuomo-Dannenburg G, Djaafara B, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Hallett T, Hamlet A, Haw D, Hayes S, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Mousa A, Nedjati-Gilani G, Nouvellet P, Okell L, Parag K, Ragonnet-Cronin M, Riley S, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Donnelly C, Ferguson Net al., 2020, SARS-CoV-2 infection prevalence on repatriation flights from Wuhan City, China, Journal of Travel Medicine, Vol: 27, Pages: 1-3, ISSN: 1195-1982

We estimated SARS-CoV-2 infection prevalence in cohorts of repatriated citizens from Wuhan to be 0.44% (95% CI: 0.19%–1.03%). Although not representative of the wider population we believe these estimates are helpful in providing a conservative estimate of infection prevalence in Wuhan City, China, in the absence of large-scale population testing early in the epidemic.

Journal article

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