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  • Journal article
    Webster HH, Nyberg T, Sinnathamby MA, Aziz NA, Ferguson N, Seghezzo G, Blomquist PB, Bridgen J, Chand M, Groves N, Myers R, Hope R, Ashano E, Lopez-Bernal J, De Angelis D, Dabrera G, Presanis AM, Thelwall Set al., 2022,

    Hospitalisation and mortality risk of SARS-COV-2 variant omicron sub-lineage BA.2 compared to BA.1 in England

    , NATURE COMMUNICATIONS, Vol: 13
  • Journal article
    Houston H, Hakki S, Pillay TD, Madon K, Derqui-Fernandez N, Koycheva A, Singanayagam A, Fenn J, Kundu R, Conibear E, Varro R, Cutajar J, Quinn V, Wang L, Narean JS, Tolosa-Wright MR, Barnett J, Kon OM, Tedder R, Taylor G, Zambon M, Ferguson N, Dunning J, Deeks JJ, Lalvani Aet al., 2022,

    Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts

    , EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
  • Journal article
    Laydon DJ, Cauchemez S, Hinsley WR, Bhatt S, Ferguson NMet al., 2022,

    Prophylactic and reactive vaccination strategies for healthcare workers against MERS-CoV

    <jats:title>Abstract</jats:title><jats:p>Several vaccines candidates are in development against Middle East respiratory syndrome–related coronavirus (MERS-CoV), which remains a major public health concern. Using individual-level data on the 2013-2014 Kingdom of Saudi Arabia epidemic, we employ counterfactual analysis on inferred transmission trees (“who-infected-whom”) to assess potential vaccine impact. We investigate the conditions under which prophylactic “proactive” campaigns would outperform “reactive” campaigns (i.e. vaccinating either before or in response to the next outbreak), focussing on healthcare workers. Spatial scale is crucial: if vaccinating healthcare workers in response to outbreaks at their hospital only, proactive campaigns perform better, unless efficacy has waned significantly. However, campaigns that react at regional or national level consistently outperform proactive campaigns. Measures targeting the animal reservoir reduce transmission linearly, albeit with wide uncertainty. Substantial reduction of MERS-CoV morbidity and mortality is possible when vaccinating healthcare workers, underlining the need for at-risk countries to stockpile vaccines when available.</jats:p>
  • Journal article
    Nyberg T, Ferguson NM, Nash SG, Webster HH, Flaxman S, Andrews N, Hinsley W, Bernal JL, Kall M, Bhatt S, Blomquist P, Zaidi A, Volz E, Aziz NA, Harman K, Funk S, Abbott S, Hope R, Charlett A, Chand M, Ghani AC, Seaman SR, Dabrera G, De Angelis D, Presanis AM, Thelwall Set al., 2022,

    Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study

    , LANCET, Vol: 399, Pages: 1303-1312, ISSN: 0140-6736
  • Journal article
    Killingley B, Mann AJ, Kalinova M, Boyers A, Goonawardane N, Zhou J, Lindsell K, Hare SS, Brown J, Frise R, Smith E, Hopkins C, Noulin N, Londt B, Wilkinson T, Harden S, McShane H, Baillet M, Gilbert A, Jacobs M, Charman C, Mande P, Nguyen-Van-Tam JS, Semple MG, Read RC, Ferguson NM, Openshaw PJ, Rapeport G, Barclay WS, Catchpole AP, Chiu Cet al., 2022,

    Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults

    , Nature Medicine, Pages: 1-27, ISSN: 1078-8956

    Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18–29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study’s primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2–4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative cor
  • Journal article
    Green WD, Ferguson NM, Cori A, 2022,

    Inferring the reproduction number using the renewal equation in heterogeneous epidemics

    , JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 19, ISSN: 1742-5689
  • Journal article
    Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, Gower C, Kall M, Groves N, O'connell A-M, Simons D, Blomquist PB, Zaidi A, Nash S, Aziz NIBA, Thelwall S, Dabrera G, Myers R, Amirthalingam G, Gharbia S, Barrett JC, Elson R, Ladhani SN, Ferguson N, Zambon M, Campbell CNJ, Brown K, Hopkins S, Chand M, Ramsay M, Bernal JLet al., 2022,

    Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant

    , NEW ENGLAND JOURNAL OF MEDICINE, Vol: 386, Pages: 1532-1546, ISSN: 0028-4793
  • Working paper
    Imai N, Gaythorpe KAM, Bhatia S, Mangal TD, Cuomo-Dannenburg G, Unwin HJT, Jauneikaite E, Ferguson NMet 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 &lt;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
  • Journal article
    Singanayagam A, Hakki S, Dunning J, Madon KJ, Crone MA, Koycheva A, Derqui-Fernandez N, Barnett JL, Whitfield MG, Varro R, Charlett A, Kundu R, Fenn J, Cutajar J, Quinn V, Conibear E, Barclay W, Freemont PS, Taylor GP, Ahmad S, Zambon M, Ferguson NM, Lalvani A, Badhan A, Dustan S, Tejpal C, Ketkar AV, Narean JS, Hammett S, McDermott E, Pillay T, Houston H, Luca C, Samuel J, Bremang S, Evetts S, Poh J, Anderson C, Jackson D, Miah S, Ellis J, Lackenby Aet al., 2022,

    Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study

    , The Lancet Infectious Diseases, Vol: 22, Pages: 183-195, ISSN: 1473-3099

    BackgroundThe SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community.MethodsBetween Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases’ vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status.FindingsThe SAR in household contacts exposed to the delta variant was 25% (95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74–120]) than for unin
  • Journal article
    Hogan AB, Wu SL, Doohan P, Watson OJ, Winskill P, Charles G, Barnsley G, Riley EM, Khoury DS, Ferguson NM, Ghani ACet al., 2022,

    The value of vaccine booster doses to mitigate the global impact of the Omicron SARS-CoV-2 variant

    <jats:title>Abstract</jats:title><jats:p>Vaccines have played a central role in mitigating severe disease and death from COVID-19 in the past 12 months. However, efficacy wanes over time and this loss of protection is being compounded by the emergence of the Omicron variant. By fitting an immunological model to population-level vaccine effectiveness data, we estimate that neutralizing antibody titres for Omicron are reduced by 3.9-fold (95% CrI 2.9–5.5) compared to the Delta variant. Under this model, we predict that 90 days after boosting with the Pfizer-BioNTech vaccine, efficacy against severe disease (admission to hospital) declines to 95.9% (95% CrI 95.4%–96.3%) against the Delta variant and 78.8% (95% CrI 75.0%–85.1%) against the Omicron variant. Integrating this immunological model within a model of SARS-CoV-2 transmission, we demonstrate that the size of the Omicron wave will depend on the degree of past exposure to infection across the population, with relatively small Omicron waves in countries that previously experienced a large Delta wave. We show that booster doses can have a major impact in mitigating the epidemic peak, although in many settings it remains possible that healthcare capacity could still be challenged. This is particularly the case in “zero-COVID” countries where there is little prior infection-induced immunity and therefore epidemic peaks will be higher. Where dose supply is limited, targeting boosters to the highest risk groups to ensure continued high protection in the face of waning immunity is of greater benefit than giving these doses as primary vaccination to younger age-groups. In many settings it is likely that health systems will be stretched, and it may therefore be necessary to maintain and/or reintroduce some level of NPIs to mitigate the worst impacts of the Omicron variant as it replaces the Delta variant.</jats:p>

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