Understanding the infection severity and epidemiological characteristics of mpox in the UK.

In May 2022, individuals infected with the monkeypox virus were detected in the UK without clear travel links to endemic areas. Understanding the clinical characteristics and infection severity of mpox is necessary for effective public health policy. The study period of this paper, from the 1st June 2022 to 30th September 2022, included 3,375 individuals that tested positive for the monkeypox virus. The posterior mean times from infection to hospital admission and length of hospital stay were 14.89 days (95% Credible Intervals (CrI): 13.60, 16.32) and 7.07 days (95% CrI: 6.07, 8.23), respectively. We estimated the modelled Infection Hospitalisation Risk to be 4.13% (95% CrI: 3.04, 5.02), compared to the overall sample Case Hospitalisation Risk (CHR) of 5.10% (95% CrI: 4.38, 5.86). The overall sample CHR was estimated to be 17.86% (95% CrI: 6.06, 33.11) for females and 4.99% (95% CrI: 4.27, 5.75) for males. A notable difference was observed between the CHRs that were estimated for each sex, which may be indicative of increased infection severity in females or a considerably lower infection ascertainment rate. It was estimated that 74.65% (95% CrI: 55.78, 86.85) of infections with the monkeypox virus in the UK were captured over the outbreak.

Diversity of symptom phenotypes in SARS-CoV-2 community infections observed in multiple large datasets.

Variability in case severity and in the range of symptoms experienced has been apparent from the earliest months of the COVID-19 pandemic. From a clinical perspective, symptom variability might indicate various routes/mechanisms by which infection leads to disease, with different routes requiring potentially different treatment approaches. For public health and control of transmission, symptoms in community cases were the prompt upon which action such as PCR testing and isolation was taken. However, interpreting symptoms presents challenges, for instance, in balancing the sensitivity and specificity of individual symptoms with the need to maximise case finding, whilst managing demand for limited resources such as testing. For both clinical and transmission control reasons, we require an approach that allows for the possibility of distinct symptom phenotypes, rather than assuming variability along a single dimension. Here we address this problem by bringing together four large and diverse datasets deriving from routine testing, a population-representative household survey and participatory smartphone surveillance in the United Kingdom. Through the use of cutting-edge unsupervised classification techniques from statistics and machine learning, we characterise symptom phenotypes among symptomatic SARS-CoV-2 PCR-positive community cases. We first analyse each dataset in isolation and across age bands, before using methods that allow us to compare multiple datasets. While we observe separation due to the total number of symptoms experienced by cases, we also see a separation of symptoms into gastrointestinal, respiratory and other types, and different symptom co-occurrence patterns at the extremes of age. In this way, we are able to demonstrate the deep structure of symptoms of COVID-19 without usual biases due to study design. This is expected to have implications for the identification and management of community SARS-CoV-2 cases and could be further applied to symptom-based management of other diseases and syndromes.

Simulation Study of Surveillance Strategies for Faster Detection of Novel SARS-CoV-2 Variants.

Earlier global detection of novel SARS-CoV-2 variants gives governments more time to respond. However, few countries can implement timely national surveillance, resulting in gaps in monitoring. The United Kingdom implemented large-scale community and hospital surveillance, but experience suggests it might be faster to detect new variants through testing England arrivals for surveillance. We developed simulations of emergence and importation of novel variants with a range of infection hospitalization rates to the United Kingdom. We compared time taken to detect the variant though testing arrivals at England borders, hospital admissions, and the general community. We found that sampling 10%-50% of arrivals at England borders could confer a speed advantage of 3.5-6 weeks over existing community surveillance and 1.5-5 weeks (depending on infection hospitalization rates) over hospital testing. Directing limited global capacity for surveillance to highly connected ports could speed up global detection of novel SARS-CoV-2 variants.

Nowcasting the 2022 mpox outbreak in England.

In May 2022, a cluster of mpox cases were detected in the UK that could not be traced to recent travel history from an endemic region. Over the coming months, the outbreak grew, with over 3000 total cases reported in the UK, and similar outbreaks occurring worldwide. These outbreaks appeared linked to sexual contact networks between gay, bisexual and other men who have sex with men. Following the COVID-19 pandemic, local health systems were strained, and therefore effective surveillance for mpox was essential for managing public health policy. However, the mpox outbreak in the UK was characterised by substantial delays in the reporting of the symptom onset date and specimen collection date for confirmed positive cases. These delays led to substantial backfilling in the epidemic curve, making it challenging to interpret the epidemic trajectory in real-time. Many nowcasting models exist to tackle this challenge in epidemiological data, but these lacked sufficient flexibility. We have developed a nowcasting model using generalised additive models that makes novel use of individual-level patient data to correct the mpox epidemic curve in England. The aim of this model is to correct for backfilling in the epidemic curve and provide real-time characteristics of the state of the epidemic, including the real-time growth rate. This model benefited from close collaboration with individuals involved in collecting and processing the data, enabling temporal changes in the reporting structure to be built into the model, which improved the robustness of the nowcasts generated. The resulting model accurately captured the true shape of the epidemic curve in real time.

The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom.

Beginning in May 2022, Mpox virus 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 modified 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. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.

Transmission dynamics of monkeypox in the United Kingdom: contact tracing study.

OBJECTIVE: To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022. DESIGN: Contact tracing study, linking data on case-contact pairs and on probable exposure dates. SETTING: Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom. PARTICIPANTS: 2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022. MAIN OUTCOME MEASURES: The incubation period and serial interval of a monkeypox infection using two bayesian time delay models-one corrected for interval censoring (ICC-interval censoring corrected) and one corrected for interval censoring, right truncation, and epidemic phase bias (ICRTC-interval censoring right truncation corrected). Growth rates of cases by reporting date, when monkeypox virus was confirmed and reported to UKHSA, were estimated using generalised additive models. RESULTS: The mean age of participants was 37.8 years and 95% reported being gay, bisexual, and other men who have sex with men (1160 out of 1213 reporting). The mean incubation period was estimated to be 7.6 days (95% credible interval 6.5 to 9.9) using the ICC model and 7.8 days (6.6 to 9.2) using the ICRTC model. The estimated mean serial interval was 8.0 days (95% credible interval 6.5 to 9.8) using the ICC model and 9.5 days (7.4 to 12.3) using the ICRTC model. Although the mean serial interval was longer than the incubation period for both models, short serial intervals were more common than short incubation periods, with the 25th centile and the median of the serial interval shorter than the incubation period. For the ICC and ICRTC models, the corresponding estimates ranged from 1.8 days (95% credible interval 1.5 to 1.8) to 1.6 days (1.4 to 1.6) shorter at the 25th centile and 1.6 days (1.5 to 1.7) to 0.8 days (0.3 to 1.2) shorter at the median. 10 out of 13 linked patients had documented pre-symptomatic transmission. Doubling times of cases declined from 9.07 days (95% confidence interval 12.63 to 7.08) on the 6 May, when the first case of monkeypox was reported in the UK, to a halving time of 29 days (95% confidence interval 38.02 to 23.44) on 1 August. CONCLUSIONS: Analysis of the instantaneous growth rate of monkeypox incidence indicates that the epidemic peaked in the UK as of 9 July and then started to decline. Short serial intervals were more common than short incubation periods suggesting considerable pre-symptomatic transmission, which was validated through linked patient level records. For patients who could be linked through personally identifiable data, four days was the maximum time that transmission was detected before symptoms manifested. An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection. The 95th centile of the serial interval was between 23 and 41 days, suggesting long infectious periods.