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BackgroundLike many other countries worldwide, the UK experienced a national outbreak of monkeypox disease in May 2022, with case numbers rising rapidly, mainly among gay, bisexual and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara–Bavaria Nordic (MVA-BN), an attenuated smallpox vaccine, was offered to high-risk GBMSM. We assessed the effectiveness of a single MVA-BN dose against monkeypox disease in high-risk GBMSM.MethodsMonkeypox cases in England were sent questionnaires collecting information on demographics, vaccination history and symptoms. Returned questionnaires with a rash onset date (or alternative proxy) between July 04 and October 09, 2022 were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method where vaccine coverage among cases is compared to coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of high-risk GBMSM. Sensitivity analysis included +/-20% differences in estimated high-risk GBMSM population size.FindingsVaccine uptake among eligible GBMSM increased steadily from July 2022, reaching 47% by October 09, 2022. Of the 363 confirmed cases, 8 occurred ≥14 days after vaccination, 32 within 0-13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness ≥14 days after a single dose was 78% (95% CI: 54%-89%), with a range of ±7% in sensitivity analyses. Vaccine effectiveness within 0–13-days after vaccination was -4% (95% CI: -50% to 29%).InterpretationA single MVA-BN dose was highly protective against monkeypox disease among high-risk GBMSM.FundingNoneResearch in contextEvidence before this studyWe searched PubMed using the terms ‘monkeypox’, ‘MVA’ and ‘vaccine’, with no time limit, and used the snowball process to identify additional relevant publications. We also searched websites of regulatory authorities (FDA, EMA) for any data used during the regulatory approval processes. We also scoped pre-print databases vaccine effectiveness studies during the current outbreak. Only publications related to the Modified Vaccinia Ankara – Bavaria Nordic (MVA-BN) vaccine were included. In the UK, MVA-BN was offered to high-risk GBMSM to control a national outbreak which began in May 2022. MVA-BN is now licensed against smallpox in the US, Europe and the UK, there are, however, limited data on vaccine effectiveness against monkeypox. Preclinical studies indicated two vaccine doses were immunogenic and generated antibody levels considered protective against smallpox. Vaccine-induced antibodies are also cross-protective against monkeypox virus in vitro and in animal models. A recent, as yet unpublished, Israeli study estimated 79% vaccine effectiveness after one dose in high-risk GBMSM, while a US study reported unvaccinated individuals to be 14 times more likely to develop monkeypox disease than vaccinated persons.Added value of this studyFew countries have recommended or introduced large-scale vaccination against the current global outbreak of monkeypox disease among GBMSM in non-endemic countries. The offer of MVA-BN to high-risk GBMSM through sexual health clinics in England provided a unique opportunity to rapidly assess vaccine effectiveness after a single dose using the case-coverage method, which involves comparing vaccine coverage in cases to vaccine coverage in the eligible population. Our vaccine effectiveness estimate of 78% at least 14 days after one MVA-BN dose is consistent with Israeli estimates and provided additional evidence of a lack of protection during the first 13 days after vaccination.Implications of all the available evidenceA single dose of MVA-BN is highly protective against monkeypox disease and provides a useful tool for outbreak control when rapid protection may be needed. Given the lack of effectiveness in the first 13 days after the first dose and a median incubation period of 8-9 days after exposure to the virus, vaccination is likely to be most effective when offered as pre-exposure rather than prophylaxis. Because of the high vaccine effectiveness after one MVA-BN dose, in outbreaks where number of at-risk individuals exceed vaccine supply of two-doses, there may be benefit in prioritising delivery of first doses at the expense of delaying the second dose.

Since May 2022, monkeypox virus (MPXV) has spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. We find that MPXV cases peaked in mid-July, declining due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. We predict cases will remain low from October 2022 to March 2023 (20-65 cases a week), and a rebound in cases due to behaviour reversion prevented by high-risk group-targeted vaccination.

In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus.We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing.Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%).DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections.UK Government Department of Health and Social Care.

ObjectiveIn September 2020, records of 15,861 SARS-CoV-2 cases failed to upload from the Second Generation Laboratory Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, resulting in a delay in the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on health outcomes: transmission events, hospitalisations, and mortality. Previously, a modelling study had suggested a substantial impact.DesignObservational studySettingEngland.PopulationIndividuals testing positive for SARS-CoV-2 and their reported contacts.Main outcome measuresSecondary attack rates (SARs), hospitalisations, and deaths amongst primary and secondary contacts were calculated, compared to all other concurrent, unaffected cases. SGSS records affected by the event were matched to CTAS records and successive contacts and cases were identified.ResultsThe initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared to the control group (3 days). This was associated with lower completion of contact tracing of primary cases in the delay group: 80% (95%CI: 79-81%) in the delay group and 83% (95%CI: 83-84%) in the control group. There was some evidence to suggest an increase in transmission to non-household contacts amongst those affected by the delay. The SAR for non-household contacts was higher amongst secondary contacts in the delay group than the control group (delay group: 7.9%, 95%CI:6.4% to 9.2%; control group: 5.9%, 95%CI: 5.3% to 6.6%). There was no evidence of a difference between the delay and control groups in the odds of hospitalisation (crude odds ratio: 1.1 (95%CI: 0.9 to 1.2) or death (crude odds ratio: 0.7 (0.1 to 4.0)) amongst secondary contacts.ConclusionsThe delay in contact tracing had a limited impact on population health outcomes.Strengths and limitations of the studyShows empirical data on the health impact of an event leading to a delay in contact tracing so can test hypotheses generated by models of the potential impact of a delay in contact tracingEstimates the extent of further transmission and odds of increased mortality or hospitalisation in up to the third generation of cases affected by the eventThe event acts as a natural experiment to describe the possible impact of contact tracing, comparing a group affected by chance by delayed contact tracing to a control group who experienced no delayContact tracing was not completed for all individuals, so the study might not capture all affected contacts or transmissions

SummaryBackgroundThe SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources.MethodsOmicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission.FindingsAnalysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16).InterpretationOur study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.FundingStudy funded by the UK Health Security Agency.

A subset of events within the UK Government Events Research Programme (ERP), developed to examine the risk of transmission of COVID-19 from attendance at events, was examined to explore the public health impact of holding mass sporting events. We used contact tracing data routinely collected through telephone interviews and online questionnaires, to describe the potential public health impact of the large sporting and cultural events on potential transmission and incidence of COVID-19. Data from the EURO 2020 matches hosted at Wembley identified very high numbers of individuals who tested positive for COVID-19 and were traced through NHS Test & Trace. This included both individuals who were potentially infectious (3036) and those who acquired their infection during the time of the Final (6376). This is in contrast with the All England Lawn Tennis Championships at Wimbledon, where there were similar number of spectators and venue capacity but there were lower total numbers of potentially infectious cases (299) and potentially acquired cases (582). While the infections associated with the EURO 2020 event may be attributed to a set of socio-cultural circumstances which are unlikely to be replicated for the forthcoming sporting season, other aspects may be important to consider including mitigations for spectators to consider such as face coverings when travelling to and from events, minimising crowding in poorly ventilated indoor spaces such as bars and pubs where people may congregate to watch events, and reducing the risk of aerosol exposure through requesting that individuals avoid shouting and chanting in large groups in enclosed spaces.

Symptoms are currently used as testing indicators for SARS-CoV-2 in England. In this study, we analysed national contact tracing data for England (NHS Test and Trace) for the period 1 December to 28 December 2021 to explore symptom differences between the variants, Delta and Omicron. We found that at least one of the symptoms currently used as indicators (fever, cough and loss of smell and taste) were reported in 61.5% of Omicron cases and 72.2% in Delta cases, suggesting that these symptoms are less predictive of Omicron infections. Nearly 40% of Omicron infections did not report any of the three key indicative symptoms, reinforcing the importance of the entire spectrum of symptoms for targeted testing. After adjusting for potential confounding factors, fever and cough were more commonly associated with Omicron infections compared to Delta, showing the importance of considering age and vaccination status when assessing symptom profiles. Sore throat was also more commonly reported in Omicron infections, and loss of smell and taste more commonly reported in Delta infections. Our study shows the value of continued monitoring of symptoms associated with SARS-CoV-2, as changes may influence the effectiveness of testing policy and case ascertainment approaches.

BackgroundTesting asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals. This study investigated the feasibility and acceptability of implementing a ‘test to enable approach’ as part of England’s tracing strategy.MethodsContacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post exposure. Asymptomatic participants with a negative LFD result were given 24 hours of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period.ResultsOf 1,760 contacts, 882 consented to daily testing, with 812 within 48 hours of exposure sent testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. 82.8% of PCR positive samples and 99.6% of PCR negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) were comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%).ConclusionThis study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.

A new one-dimensional aluminum phosphate has been synthesized under solvothermal conditions at 180°C in the presence of 4,4′-dipyridine and the structure solved using room-temperature single-crystal X-ray diffraction data. ([C10N2H9]+[H2AlP2O8]−, Mr=376.13, triclinic, space groupP-1,a=4.9169(9) A,b=10.696(3) A, γ=14.660(8) A, α=107.84(3)°, β=95.68(3)°, γ=99.91(2)°,V=713.8(1) A3,Z=2, 1626 observed data measured with (I>3(σ(I)),R=4.56% andRw=5.42%). The structure consists of chains containing 4-membered rings of AlO4and PO4tetrahedra constituting a backbone from which hang “pendant” PO2(OH)2groups. The chains are held together by hydrogen bonding via the dipyridyl cations.

We examine the relationship between international trade and regional American credit markets. The evidence presented suggests that foreign payment flows had a significant effect on the level of interest rates in the East North Central, West North Central, Pacific, and Southern regions of the United States.