Social connection and mortality in UK Biobank: a prospective cohort analysis.

BACKGROUND: Components of social connection are associated with mortality, but research examining their independent and combined effects in the same dataset is lacking. This study aimed to examine the independent and combined associations between functional and structural components of social connection and mortality. METHODS: Analysis of 458,146 participants with full data from the UK Biobank cohort linked to mortality registers. Social connection was assessed using two functional (frequency of ability to confide in someone close and often feeling lonely) and three structural (frequency of friends/family visits, weekly group activities, and living alone) component measures. Cox proportional hazard models were used to examine the associations with all-cause and cardiovascular disease (CVD) mortality. RESULTS: Over a median of 12.6 years (IQR 11.9-13.3) follow-up, 33,135 (7.2%) participants died, including 5112 (1.1%) CVD deaths. All social connection measures were independently associated with both outcomes. Friends/family visit frequencies < monthly were associated with a higher risk of mortality indicating a threshold effect. There were interactions between living alone and friends/family visits and between living alone and weekly group activity. For example, compared with daily friends/family visits-not living alone, there was higher all-cause mortality for daily visits-living alone (HR 1.19 [95% CI 1.12-1.26]), for never having visits-not living alone (1.33 [1.22-1.46]), and for never having visits-living alone (1.77 [1.61-1.95]). Never having friends/family visits whilst living alone potentially counteracted benefits from other components as mortality risks were highest for those reporting both never having visits and living alone regardless of weekly group activity or functional components. When all measures were combined into overall functional and structural components, there was an interaction between components: compared with participants defined as not isolated by both components, those considered isolated by both components had higher CVD mortality (HR 1.63 [1.51-1.76]) than each component alone (functional isolation 1.17 [1.06-1.29]; structural isolation 1.27 [1.18-1.36]). CONCLUSIONS: This work suggests (1) a potential threshold effect for friends/family visits, (2) that those who live alone with additional concurrent markers of structural isolation may represent a high-risk population, (3) that beneficial associations for some types of social connection might not be felt when other types of social connection are absent, and (4) considering both functional and structural components of social connection may help to identify the most isolated in society.

True prevalence of long-COVID in a nationwide, population cohort study.

Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.

Natural history of long-COVID in a nationwide, population cohort study.

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.

Chronic pain and COVID-19 hospitalisation and mortality: a UK Biobank cohort study.

ABSTRACT: The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P -value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P -value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

The influence of socioeconomic status on the association between unhealthy lifestyle factors and adverse health outcomes: a systematic review.

Background: Combinations of lifestyle factors (LFs) and socioeconomic status (SES) are independently associated with cardiovascular disease (CVD), cancer, and mortality. Less advantaged SES groups may be disproportionately vulnerable to unhealthy LFs but interactions between LFs and SES remain poorly understood. This review aimed to synthesise the available evidence for whether and how SES modifies associations between combinations of LFs and adverse health outcomes. Methods: Systematic review of studies that examine associations between combinations of >3 LFs (eg.smoking/physical activity/diet) and health outcomes and report data on SES (eg.income/education/poverty-index) influences on associations. Databases (PubMed/EMBASE/CINAHL), references, forward citations, and grey-literature were searched from inception to December 2021. Eligibility criteria were analyses of prospective adult cohorts that examined all-cause mortality or CVD/cancer mortality/incidence. Results: Six studies (n=42,467-399,537; 46.5-56.8 years old; 54.6-59.3% women) of five cohorts were included. All examined all-cause mortality; three assessed CVD/cancer outcomes. Four studies observed multiplicative interactions between LFs and SES, but in opposing directions. Two studies tested for additive interactions; interactions were observed in one cohort (UK Biobank) and not in another (National Health and Nutrition Examination Survey (NHANES)). All-cause mortality HRs (95% confidence intervals) for unhealthy LFs (versus healthy LFs) from the most advantaged SES groups ranged from 0.68 (0.32-1.45) to 4.17 (2.27-7.69). Equivalent estimates from the least advantaged ranged from 1.30 (1.13-1.50) to 4.00 (2.22-7.14). In 19 analyses (including sensitivity analyses) of joint associations between LFs, SES, and all-cause mortality, highest all-cause mortality was observed in the unhealthiest LF-least advantaged suggesting an additive effect. Conclusions: Limited and heterogenous literature suggests that the influence of SES on associations between combinations of unhealthy LFs and adverse health could be additive but remains unclear. Additional prospective analyses would help clarify whether SES modifies associations between combinations of unhealthy LFs and health outcomes. Registration: Protocol is registered with PROSPERO (CRD42020172588;25 June 2020).

Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.

With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.

Widening or narrowing inequalities? The equity implications of digital tools to support COVID-19 contact tracing: A qualitative study.

BACKGROUND: As digital tools are increasingly used to support COVID-19 contact tracing, the equity implications must be considered. As part of a study to understand the public's views of digital contact tracing tools developed for the national 'Test and Protect' programme in Scotland, we aimed to explore the views of groups often excluded from such discussions. This paper reports on their views about the potential for contact tracing to exacerbate inequalities. METHODS: A qualitative study was carried out; interviews were conducted with key informants from organizations supporting people in marginalized situations, followed by interviews and focus groups with people recruited from these groups. Participants included, or represented, minority ethnic groups, asylum seekers and refugees and those experiencing multiple disadvantage including severe and enduring poverty. RESULTS: A total of 42 people participated: 13 key informants and 29 members of the public. While public participants were supportive of contact tracing, key informants raised concerns. Both sets of participants spoke about how contact tracing, and its associated digital tools, might increase inequalities. Barriers included finances (inability to afford smartphones or the data to ensure access to the internet); language (digital tools were available only in English and required a degree of literacy, even for English speakers); and trust (many marginalized groups distrusted statutory organizations and there were concerns that data may be passed to other organizations). One strength was that NHS Scotland, the data guardian, is seen as a generally trustworthy organization. Poverty was recognized as a barrier to people's ability to self-isolate. Some participants were concerned about giving contact details of individuals who might struggle to self-isolate for financial reasons. CONCLUSIONS: The impact of contact tracing and associated digital tools on marginalized populations needs careful monitoring. This should include the contact tracing process and the ability of people to self-isolate. Regular clear messaging from trusted groups and community members could help maintain trust and participation in the programme. PATIENT AND PUBLIC CONTRIBUTION: Our patient and public involvement coapplicant, L. L., was involved in all aspects of the study including coauthorship. Interim results were presented to our local Public and Patient Involvement and Engagement Group, who commented on interpretation and made suggestions about further recruitment.

The association between a lifestyle score, socioeconomic status, and COVID-19 outcomes within the UK Biobank cohort.

BACKGROUND: Infection with SARS-CoV-2 virus (COVID-19) impacts disadvantaged groups most. Lifestyle factors are also associated with adverse COVID-19 outcomes. To inform COVID-19 policy and interventions, we explored effect modification of socioeconomic-status (SES) on associations between lifestyle and COVID-19 outcomes. METHODS: Using data from UK-Biobank, a large prospective cohort of 502,536 participants aged 37-73 years recruited between 2006 and 2010, we assigned participants a lifestyle score comprising nine factors. Poisson regression models with penalised splines were used to analyse associations between lifestyle score, deprivation (Townsend), and COVID-19 mortality and severe COVID-19. Associations between each exposure and outcome were examined independently before participants were dichotomised by deprivation to examine exposures jointly. Models were adjusted for sociodemographic/health factors. RESULTS: Of 343,850 participants (mean age > 60 years) with complete data, 707 (0.21%) died from COVID-19 and 2506 (0.76%) had severe COVID-19. There was evidence of a nonlinear association between lifestyle score and COVID-19 mortality but limited evidence for nonlinearity between lifestyle score and severe COVID-19 and between deprivation and COVID-19 outcomes. Compared with low deprivation, participants in the high deprivation group had higher risk of COVID-19 outcomes across the lifestyle score. There was evidence for an additive interaction between lifestyle score and deprivation. Compared with participants with the healthiest lifestyle score in the low deprivation group, COVID-19 mortality risk ratios (95% CIs) for those with less healthy scores in low versus high deprivation groups were 5.09 (1.39-25.20) and 9.60 (4.70-21.44), respectively. Equivalent figures for severe COVID-19 were 5.17 (2.46-12.01) and 6.02 (4.72-7.71). Alternative SES measures produced similar results. CONCLUSIONS: Unhealthy lifestyles are associated with higher risk of adverse COVID-19, but risks are highest in the most disadvantaged, suggesting an additive influence between SES and lifestyle. COVID-19 policy and interventions should consider both lifestyle and SES. The greatest public health benefit from lifestyle focussed COVID-19 policy and interventions is likely to be seen when greatest support for healthy living is provided to the most disadvantaged groups.

Patient and practitioner views on cancer risk discussions in primary care: a qualitative study.

BACKGROUND: It is estimated that nearly 600 000 cancer cases in the UK could have been avoided in the past 5 years if people had healthier lifestyles, with the principle modifiable risk factors being smoking, obesity, alcohol consumption, and inactivity. There is growing interest in the use of cancer risk information in general practice to encourage lifestyle modification. AIM: To explore the views and experiences of patients and practitioners in relation to cancer prevention and cancer risk discussions in general practice. DESIGN & SETTING: Qualitative study among patients and practitioners in general practices in Glasgow, UK. METHOD: Semi-structured interviews were conducted with nine practitioners (five GPs and four practice nurses, recruited purposively from practices based on list size and deprivation status), and 13 patients (aged 30-60 years, with two or more specified comorbidities). RESULTS: Currently, cancer risk discussions focus on smoking and cancer, with links between alcohol and/or obesity and cancer rarely made. There was support for the use of the personalised cancer risk tool as an additional resource in primary care. Practitioners felt practice nurses were best placed to use it. Use in planned appointments (for example, chronic disease reviews) was preferred over opportunistic use. Concerns were expressed, however, about generating anxiety, time constraints, and widening inequalities. CONCLUSION: Health behaviour change is complex and the provision of information alone is unlikely to have significant effects. Personalised risk tools may have a role, but important concerns about their use remain, particularly in areas of socioeconomic disadvantage.

Understanding the influence of socioeconomic status on the association between combinations of lifestyle factors and adverse health outcomes: a systematic review protocol.

INTRODUCTION: Combinations of unhealthy lifestyle factors are strongly associated with mortality, cardiovascular disease (CVD) and cancer. It is unclear how socioeconomic status (SES) affects those associations. Lower SES groups may be disproportionately vulnerable to the effects of unhealthy lifestyle factors compared with higher SES groups via interactions with other factors associated with low SES (eg, stress) or via accelerated biological ageing. This systematic review aims to synthesise studies that examine how SES moderates the association between lifestyle factor combinations and adverse health outcomes. Greater understanding of how lifestyle risk varies across socioeconomic spectra could reduce adverse health by (1) identifying novel high-risk groups or targets for future interventions and (2) informing research, policy and interventions that aim to support healthy lifestyles in socioeconomically deprived communities. METHODS AND ANALYSIS: Three databases will be searched (PubMed, EMBASE, CINAHL) from inception to March 2020. Reference lists, citations and grey literature will also be searched. Inclusion criteria are: (1) prospective cohort studies; (2) investigations of two key exposures: (a) lifestyle factor combinations of at least three lifestyle factors (eg, smoking, physical activity and diet) and (b) SES (eg, income, education or poverty index); (3) an assessment of the impact of SES on the association between combinations of unhealthy lifestyle factors and health outcomes; (4) at least one outcome from-mortality (all cause, CVD and cancer), CVD or cancer incidence. Two independent reviewers will screen titles, abstracts and full texts of included studies. Data extraction will focus on cohort characteristics, exposures, direction and magnitude of SES effects, methods and quality (via Newcastle-Ottawa Scale). If appropriate, a meta-analysis, pooling the effects of SES, will be performed. Alternatively, a synthesis without meta-analysis will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required. Results will be disseminated via peer-reviewed publication, professional networks, social media and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020172588.

Correction: Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort.

[This corrects the article DOI: 10.1371/journal.pone.0238091.].

Implementing social prescribing in primary care in areas of high socioeconomic deprivation: process evaluation of the 'Deep End' community Links Worker Programme.

BACKGROUND: Social prescribing involving primary care-based 'link workers' is a key UK health policy that aims to reduce health inequalities. However, the process of implementation of the link worker approach has received little attention despite this being central to the desired impact and outcomes. AIM: To explore the implementation process of such an approach in practice. DESIGN AND SETTING: Qualitative process evaluation of the 'Deep End' Links Worker Programme (LWP) over a 2-year period, in seven general practices in deprived areas of Glasgow. METHOD: The study used thematic analysis to identify the extent of LWP integration in each practice and the key factors associated with implementation. Analysis was informed by normalisation process theory (NPT). RESULTS: Only three of the seven practices fully integrated the LWP into routine practice within 2 years, based on the NPT constructs of coherence, cognitive participation, and collective action. Compared with 'partially integrated practices', 'fully integrated practices' had better shared understanding of the programme among staff, higher staff engagement with the LWP, and were implementing all aspects of the LWP at patient, practice, and community levels of intervention. Successful implementation was associated with GP buy-in, collaborative leadership, good team dynamics, link worker support, and the absence of competing innovations. CONCLUSION: Even in a well-resourced government-funded programme, the majority of practices involved had not fully integrated the LWP within the first 2 years. Implementing social prescribing and link workers within primary care at scale is unlikely to be a 'quick fix' for mitigating health inequalities in deprived areas.

'Reluctant pioneer': A qualitative study of doctors' experiences as patients with long COVID.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has had far-reaching effects upon lives, healthcare systems and society. Some who had an apparently 'mild' COVID-19 infection continue to suffer from persistent symptoms, including chest pain, breathlessness, fatigue, cognitive impairment, paraesthesia, muscle and joint pains. This has been labelled 'long COVID'. This paper reports the experiences of doctors with long COVID. METHODS: A qualitative study; interviews with doctors experiencing persistent symptoms were conducted by telephone or video call. Interviews were transcribed and analysis conducted using an inductive and thematic approach. RESULTS: Thirteen doctors participated. The following themes are reported: making sense of symptoms, feeling let down, using medical knowledge and connections, wanting to help and be helped, combining patient and professional identity. Experiencing long COVID can be transformative: many expressed hope that good would come of their experiences. Distress related to feelings of being 'let down' and the hard work of trying to access care. Participants highlighted that they felt better able to care for, and empathize with, patients with chronic conditions, particularly where symptoms are unexplained. CONCLUSIONS: The study adds to the literature on the experiences of doctors as patients, in particular where evidence is emerging and the patient has to take the lead in finding solutions to their problems and accessing their own care. PATIENT AND PUBLIC CONTRIBUTION: The study was developed with experts by experience (including co-authors HA and TAB) who contributed to the protocol and ethics application, and commented on analysis and implications. All participants were given the opportunity to comment on findings.

Comparison of two different frailty measurements and risk of hospitalisation or death from COVID-19: findings from UK Biobank.

BACKGROUND: Frailty has been associated with worse prognosis following COVID-19 infection. While several studies have reported the association between frailty and COVID-19 mortality or length of hospital stay, there have been no community-based studies on the association between frailty and risk of severe infection. Considering that different definitions have been identified to assess frailty, this study aimed to compare the association between frailty and severe COVID-19 infection in UK Biobank using two frailty classifications: the frailty phenotype and the frailty index. METHODS: A total of 383,845 UK Biobank participants recruited 2006-2010 in England (211,310 [55.1%] women, baseline age 37-73 years) were included. COVID-19 test data were provided by Public Health England (available up to 28 June 2020). An adapted version of the frailty phenotype derived by Fried et al. was used to define frailty phenotype (robust, pre-frail, or frail). A previously validated frailty index was derived from 49 self-reported questionnaire items related to health, disease and disability, and mental wellbeing (robust, mild frailty, and moderate/severe frailty). Both classifications were derived from baseline data (2006-2010). Poisson regression models with robust standard errors were used to analyse the associations between both frailty classifications and severe COVID-19 infection (resulting in hospital admission or death), adjusted for sociodemographic and lifestyle factors. RESULTS: Of UK Biobank participants included, 802 were admitted to hospital with and/or died from COVID19 (323 deaths and 479 hospitalisations). After analyses were adjusted for sociodemographic and lifestyle factors, a higher risk of COVID-19 was observed for pre-frail (risk ratio (RR) 1.47 [95% CI 1.26; 1.71]) and frail (RR 2.66 [95% CI 2.04; 3.47]) individuals compared to those classified as robust using the frailty phenotype. Similar results were observed when the frailty index was used (RR mildly frail 1.46 [95% CI 1.26; 1.71] and RR moderate/severe frailty 2.43 [95% CI 1.91; 3.10]). CONCLUSIONS: Frailty was associated with a higher risk of severe COVID-19 infection resulting in hospital admission or death, irrespective of how it was measured and independent of sociodemographic and lifestyle factors. Public health strategies need to consider the additional risk that COVID-19 poses in individuals with frailty, including which additional preventive measures might be required.

Finding the 'right' GP: a qualitative study of the experiences of people with long-COVID.

BACKGROUND: An unknown proportion of people who had an apparently mild COVID-19 infection continue to suffer with persistent symptoms, including chest pain, shortness of breath, muscle and joint pains, headaches, cognitive impairment ('brain fog'), and fatigue. Post-acute COVID-19 ('long-COVID') seems to be a multisystem disease, sometimes occurring after a mild acute illness; people struggling with these persistent symptoms refer to themselves as 'long haulers'. AIM: To explore experiences of people with persisting symptoms following COVID-19 infection, and their views on primary care support received. DESIGN & SETTING: Qualitative methodology, with semi-structured interviews to explore perspectives of people with persisting symptoms following suspected or confirmed COVID-19 infection. Participants were recruited via social media between July-August 2020. METHOD: Interviews were conducted by telephone or video call, digitally recorded, and transcribed with consent. Thematic analysis was conducted applying constant comparison techniques. People with experience of persisting symptoms contributed to study design and data analysis. RESULTS: This article reports analysis of 24 interviews. The main themes include: the ' hard and heavy work ' of enduring and managing symptoms and accessing care; living with uncertainty, helplessness and fear, particularly over whether recovery is possible; the importance of finding the 'right' GP (understanding, empathy, and support needed); and recovery and rehabilitation: what would help? CONCLUSION: This study will raise awareness among primary care professionals, and commissioners, of long-COVID and the range of symptoms people are experiencing. Patients require their GP to believe their symptoms and to demonstrate empathy and understanding. Ongoing support by primary care professionals during recovery and rehabilitation is crucial.

Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort.

BACKGROUND: It is now well recognised that the risk of severe COVID-19 increases with some long-term conditions (LTCs). However, prior research primarily focuses on individual LTCs and there is a lack of data on the influence of multimorbidity (≥2 LTCs) on the risk of COVID-19. Given the high prevalence of multimorbidity, more detailed understanding of the associations with multimorbidity and COVID-19 would improve risk stratification and help protect those most vulnerable to severe COVID-19. Here we examine the relationships between multimorbidity, polypharmacy (a proxy of multimorbidity), and COVID-19; and how these differ by sociodemographic, lifestyle, and physiological prognostic factors. METHODS AND FINDINGS: We studied data from UK Biobank (428,199 participants; aged 37-73; recruited 2006-2010) on self-reported LTCs, medications, sociodemographic, lifestyle, and physiological measures which were linked to COVID-19 test data. Poisson regression models examined risk of COVID-19 by multimorbidity/polypharmacy and effect modification by COVID-19 prognostic factors (age/sex/ethnicity/socioeconomic status/smoking/physical activity/BMI/systolic blood pressure/renal function). 4,498 (1.05%) participants were tested; 1,324 (0.31%) tested positive for COVID-19. Compared with no LTCs, relative risk (RR) of COVID-19 in those with 1 LTC was no higher (RR 1.12 (CI 0.96-1.30)), whereas those with ≥2 LTCs had 48% higher risk; RR 1.48 (1.28-1.71). Compared with no cardiometabolic LTCs, having 1 and ≥2 cardiometabolic LTCs had a higher risk of COVID-19; RR 1.28 (1.12-1.46) and 1.77 (1.46-2.15), respectively. Polypharmacy was associated with a dose response higher risk of COVID-19. All prognostic factors were associated with a higher risk of COVID-19 infection in multimorbidity; being non-white, most socioeconomically deprived, BMI ≥40 kg/m2, and reduced renal function were associated with the highest risk of COVID-19 infection: RR 2.81 (2.09-3.78); 2.79 (2.00-3.90); 2.66 (1.88-3.76); 2.13 (1.46-3.12), respectively. No multiplicative interaction between multimorbidity and prognostic factors was identified. Important limitations include the low proportion of UK Biobank participants with COVID-19 test data (1.05%) and UK Biobank participants being more affluent, healthier and less ethnically diverse than the general population. CONCLUSIONS: Increasing multimorbidity, especially cardiometabolic multimorbidity, and polypharmacy are associated with a higher risk of developing COVID-19. Those with multimorbidity and additional factors, such as non-white ethnicity, are at heightened risk of COVID-19.