The impact of Long COVID on Health-Related Quality-of-life using OpenPROMPT (preprint)

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. Methods With the approval of NHS England, we developed OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Results We used data from 6,070 participants where 24.7% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a high probability of reporting loss in quality-of-life (OR: 22, 95% CI:12.35-39.29) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 60.2, 95% CI: 27.79-130.57) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Conclusions We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease.

Ethnic differences in the indirect impacts of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: An observational cohort study using OpenSAFELY (preprint)

Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods We conducted a cohort study using OpenSAFELY (2018-2022). We grouped ethnicity (exposure), into five categories: White, South Asian, Black, Other, Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (e.g., blood pressure measurements) before and after 23rd March 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to: diabetes, cardiovascular disease, respiratory disease, and mental health before and after 23rd March 2020. Findings Of 14,930,356 adults in 2020 with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to White. There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in White ethnicity. Relatively, ethnic differences narrowed for heart failure admission in those of Asian and Black ethnicity compared to White. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation Our study suggests ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding LSHTM COVID-19 Response Grant (DONAT15912).

Long-term health-related quality of life in non-hospitalised COVID-19 cases with confirmed SARS-CoV-2 infection in England: Longitudinal analysis and cross-sectional comparison with controls (preprint)

Background This study measured the long-term health-related quality of life of non-hospitalised COVID-19 cases with PCR-confirmed SARS-CoV-2(+) infection using the recommended instrument in England (the EQ-5D). Methods Prospective cohort study of SARS-CoV-2(+) cases aged 12-85 years and followed up for six months from 01 December 2020, with cross-sectional comparison to SARS-CoV-2(-) controls. Main outcomes were loss of quality-adjusted life days (QALDs); physical symptoms; and COVID-19-related private expenditures. We analysed results using multivariable regressions with post-hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on non-prescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 15.9 (95%-CI: 12.1, 19.7) QALDs, while those reporting symptoms at month 6 lost 34.1 (29.0, 39.2) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 21% of the total COVID-19-related disease burden in England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. summary Losses of health-related quality of life in non-hospitalised COVID-19 cases increase by age and for cases with symptoms after 6 months. At a population level, at least 21% of the total COVID-19-related disease burden in England is attributable to morbidity.

Localising Vaccination Services: Qualitative Insights on an Orthodox Jewish Collaboration with Public health during the UK coronavirus Vaccine Programme (preprint)

Ethnic and religious minorities have been disproportionately affected by the SARS-CoV-2 pandemic and are less likely to accept coronavirus vaccinations. Orthodox (Haredi) Jewish neighbourhoods in England experienced high incidences of SARS-CoV-2 in 2020-21 and measles outbreaks (2018-19) due to suboptimal childhood vaccination coverage. The objective of our study was to explore how the coronavirus vaccination programme (CVP) was co-delivered between public health services and an Orthodox Jewish health organisation. Methods: included 28 semi-structured interviews conducted virtually with public health professionals, community welfare and religious representatives, and household members. We examined CVP delivery from the perspectives of those involved in organising services and vaccine beneficiaries. Interview data was contextualised within debates of the CVP in Orthodox (Haredi) Jewish print and social media. Thematic analysis generated five considerations: i) Prior immunisation-related collaboration with public health services carved a role for Jewish health organisations to host and promote coronavirus vaccination sessions, distribute appointments, and administer vaccines ii) Public health services maintained responsibility for training, logistics, and maintaining vaccination records; iii) The localised approach to service delivery promoted vaccination in a minority with historically suboptimal levels of coverage; iv) Co-delivery promoted trust in the CVP, though a minority of participants maintained concerns around safety; v) Provision of CVP information and stakeholders’ response to situated (context-specific) challenges and concerns. Drawing on this example of CVP co-delivery, we propose that a localised approach to delivering immunisation programmes could address service provision gaps in ways that involve trusted community organisations. Localisation of vaccination services can include communication or implementation strategies, but both approaches involve consideration of investment, engagement and coordination, which are not cost-neutral. Localising vaccination services in collaboration with welfare groups raises opportunities for the on-going CVP and other immunisation programmes, and constitutes an opportunity for ethnic and religious minorities to collaborate in safeguarding community health.

The impact of co-circulating pathogens on SARS-CoV-2/COVID-19 surveillance: How concurrent epidemics may decrease true SARS-CoV-2 percent positivity (preprint)

Background Circulation of non-SARS-CoV-2 respiratory viruses during the COVID-19 pandemic may alter quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. Here, we assess the impact of an increased circulation of other respiratory viruses on the monitoring of positivity rates of SARS-CoV-2 and interpretation of surveillance data. Methods Using a multi-pathogen Susceptible-Exposed-Infectious-Recovered (SEIR) transmission model formalizing co-circulation of SARS-CoV-2 and another respiratory we assess how an outbreak of secondary virus may inflate the number of SARS-CoV-2 tests and affect the interpretation of COVID-19 surveillance data. Using simulation, we assess to what extent the use of multiplex PCR tests on a subsample of symptomatic individuals can support correction of the observed SARS-CoV-2 percent positive during other virus outbreaks and improve surveillance quality. Results Model simulations demonstrated that a non-SARS-CoV-2 epidemic creates an artificial decrease in the observed percent positivity of SARS-CoV-2, with stronger effect during the growth phase, until the peak is reached. We estimate that performing one multiplex test for every 1,000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percent positive. Conclusions This study highlights that co-circulating respiratory viruses can disrupt SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex PCR, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance. Summary COVID-19 surveillance indicators may be impacted by increased co-circulation of other respiratory viruses delaying control measure implementation. Continued surveillance through multiplex PCR testing in a subsample of the symptomatic population may play a role in fixing this problem.

Exploring Equity in Health and Poverty Impacts of Control Measures for SARS-CoV-2 in Six Countries (preprint)

Background: Policy makers need to be rapidly informed about the potential equity consequences of different COVID-19 strategies, alongside their broader health and economic impacts. While there are complex models to inform both potential health and macro-economic impact, there are few tools available to rapidly assess potential equity impacts of interventions.Methods: We created an economic model to simulate the impact of lockdown measures in Pakistan, Georgia, Chile, United Kingdom, Philippines, and South Africa. We consider impact of lockdown in terms of inability to socially distance, and income loss during lockdown, and tested the impact of assumptions on social protection coverage in a scenario analysis.Findings: In all examined countries, lower socioeconomic quintiles were likely to experience disproportionately more income loss and greater inability to socially distance during lockdown. Improving social protection increased the percentage of the workforce able to socially distance from 40% (30% Chile - 55% UK) to 60% (57% Chile - 67% UK). We estimate the cost of this social protection would be equivalent to an average of 0.5% GDP.Interpretation: We illustrate the potential for using publicly available data to rapidly assess the equity implications of social protection and non-pharmaceutical intervention policy. We highlight potential for social protection to mitigate inequitable health and economic impacts of lockdown. Although social protection is usually targeted to the poorest, middle quintiles will likely also need support as they suffer the worst income losses and are disproportionately more exposed.Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [grant number 221303/Z/20/Z].Declaration of Interests: We declare no competing interests.

Key Questions for Modelling COVID-19 Exit Strategies (preprint)

Combinations of intense non-pharmaceutical interventions ('lockdowns') were introduced in countries worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement lockdown exit strategies that allow restrictions to be relaxed while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, will allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. The roadmap requires a global collaborative effort from the scientific community and policy-makers, and is made up of three parts: i) improve estimation of key epidemiological parameters; ii) understand sources of heterogeneity in populations; iii) focus on requirements for data collection, particularly in Low-to-Middle-Income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.

Susceptibility to and transmission of COVID-19 amongst children and adolescents compared with adults: a systematic review and meta-analysis (preprint)

ImportanceThe degree to which children and young people are infected by and transmit the SARS-CoV-2 virus is unclear. The role of children and young people in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns and behaviour. ObjectiveWe undertook a rapid systematic review to address the question "What is the susceptibility to and transmission of SARS-CoV-2 by children and adolescents compared with adults?" Data sourcesWe searched PubMed and medRxiv up to 28 July 2020 and identified 13,926 studies, with additional studies identified through handsearching of cited references and professional contacts. Study SelectionWe included studies which provided data on the prevalence of SARS-CoV-2 in children and young people (<20 years) compared with adults derived from contact-tracing or population-screening. We excluded single household studies. Data extraction and SynthesisWe followed PRISMA guidelines for abstracting data, independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random effects meta-analysis was undertaken. Main OutcomesSecondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population-screening studies) amongst children and young people compared with adults. Results32 studies met inclusion criteria; 18 contact-tracing and 14 population-screening. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (0.37, 0.85) with substantial heterogeneity (95%). Three school contact tracing studies found minimal transmission by child or teacher index cases. Findings from population-screening studies were heterogenous and were not suitable for meta-analysis. The majority of studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. ConclusionsThere is preliminary evidence that children and young people have lower susceptibility to SARS-CoV-2, with a 43% lower odds of being an infected contact. There is weak evidence that children and young people play a lesser role in transmission of SARS-CoV-2 at a population level. Our study provides no information on the infectivity of children. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the evidence on the susceptibility and transmission of children and young people to SARS-CoV-2 in comparison with adults? FindingsIn this systematic review and meta-analysis, children and young people under 18-20 years had an 435 lower odds of secondary infection of with SARS-CoV-2 compared to adults 20 years plus, a significant difference. This finding was most marked in children under 12-14 years. Data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults. MeaningWe found preliminary evidence that children have a lower susceptibility for SARS-CoV-2 infection compared with adults, although data for adolescents is less clear. The role that children and young people play in transmission of this pandemic remains unclear.

The Effect of Control Strategies that Reduce Social Mixing on Outcomes of the COVID-19 Epidemic in Wuhan, China (preprint)

Background: In December 2019, a novel strain of SARS-CoV-2 emerged in Wuhan, China. Since then, the city of Wuhan has taken unprecedented measures and efforts in response to the outbreak. Methods: We quantified the effects of control measures on population contact patterns in Wuhan, China, to assess their effects on the progression of the outbreak. We included the latest estimates of epidemic parameters from a transmission model fitted to data on local and internationally exported cases from Wuhan in the age-structured epidemic framework. Further, we looked at the age-distribution of cases. Lastly, we simulated lifting of the control measures by allowing people to return to work in a phased-in way, and looked at the effects of returning to work at different stages of the underlying outbreak. Findings: Changes in mixing patterns may have contributed to reducing the number of infections in mid-2020 by 92% (interquartile range: 66–97%). There are benefits to sustaining these measures until April in terms of reducing the height of the peak, overall epidemic size in mid-2020 and probability that a second peak may occur after return to work. However, the modelled effects of social distancing measures vary by the duration of infectiousness and the role school children play in the epidemic. Interpretation: Restrictions on activities in Wuhan, if maintained until April, would likely contribute to the reduction and delay the epidemic size and peak, respectively. However, there are some limitations to the analysis, including large uncertainties around estimates of R0 and the duration of infectiousness.Funding: KP, YL, MJ, and PK were funded by the Bill & Melinda Gates Foundation (grant number INV003174), YL and MJ were funded by the National Institute for Health Research (NIHR) (16/137/109), TWR and AJK were funded by the Wellcome Trust (grant number 206250/Z/17/Z), RME was funded by HDR UK (grant number MR/S003975/1), and ND was funded by NIHR (HPRU-2012-10096).This research was partly funded by the National Institute for Health Research (NIHR) (16/137/109) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care. We would like to acknowledge (in a randomised order) the other members of the London School of Hygiene & Tropical Medicine COVID-19 modelling group, who contributed to this work: Stefan Flasche, Samuel Clifford, Carl A B Pearson, James D Munday, Sam Abbott, Hamish Gibbs, Alicia Rosello, Billy J Quilty, Thibaut Jombart, Fiona Sun, Charlie Diamond, Amy Gimma, Kevin van Zandvoort, Sebastian Funk, Christopher I Jarvis, W John Edmunds, Nikos I Bosse, and Joel Hellewell. Their funding sources are as follows: Stefan Flasche and Sam Clifford (Sir Henry Dale Fellowship [grant number 208812/Z/17/Z]); Billy J Quilty, Fiona Sun, and Charlie Diamond (NIHR [grant number 16/137/109]); Joel Hellewell, Sam Abbott, James D Munday, and Sebastian Funk (Wellcome Trust [grant number 210758/Z/18/Z] ); Amy Gimma and Christopher I Jarvis (Global Challenges Research Fund [grant number ES/P010873/1]); Hamish Gibbs (Department of Health and Social Care [grant number ITCRZ 03010]); Alicia Rosello (NIHR [grant number PROD-1017-20002]); Thibaut Jombart (RCUK/ESRC [grant number ES/P010873/1], UK PH RST, NIHR HPRU Modelling Methodology); Kevin van Zandvoort (Elrha’s Research for Health in Humanitarian Crises (R2HC) Programme, UK Government (DFID), Wellcome Trust, NIHR).Declaration of Interest: The authors declare no competing interests.