Activity of the spleen and bone marrow in relation to cardio-pulmonary injury in patients with acute covid-19 evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging

ObjectiveCOVID-19 primarily causes pneumonitis but can also cause myocarditis. Injury may be due to a generalised inflammatory immune process or by direct viral infection. Using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and cardiac magnetic resonance (CMR) imaging we correlated the metabolic activity/injury between the reticuloendothelial system (bone marrow [BM] and spleen) and myocardial/pulmonary tissue.Methods18F-FDG-PET/CT (n=29, fasted n=27) and CMR (n=23) were performed on hospitalised patients with acute COVID-19. 18F-FDG PET/CT standardised uptake values (SUV) were measured in the spleen, spinal BM, myocardial and pulmonary tissue. Cardiac target-to-background ratio (TBR) was calculated by indexing to blood-pool SUV. Myocarditis was assessed using the sensitive 2018 Lake Louise criteria (LLC), and viral load (by cycle threshold).Results13 patients had myocarditis on CMR (57%), 8 (30%) visually on 18F-FDG-PET/CT. There was no statistical difference comparing LLC positive and negative patients for BM (4.21±0.30, 4.98±0.56, P=0.23), spleen (4.40±0.40, 5.15±0.08, P=0.38) and lung (4.08±0.72, 4.16±0.91, P=0.94) SUV. Lung SUV was significantly associated with BM (r=0.61, P<0.001) and spleen (r=0.48, P<0.05) SUV. Cardiac TBR, T1 and T2 mapping showed no significant association with BM and spleen SUV (P>0.05 for all). Cycle threshold did not correlate with either cardiac TBR and T1 or T2 (p>0.05 for all).ConclusionReticuloendothelial system activation strongly correlated with lung activity, suggesting pulmonary injury is part of a systemic inflammatory process. Cardiac inflammation was not associated with either spleen, BM or viral load, suggesting injury is multifactorial.

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.

Symptoms and risk factors for long COVID in non-hospitalized adults.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

Unscheduled care pathways in patients with myocardial infarction in Scotland.

OBJECTIVE: Treatment of acute myocardial infarction (MI) requires rapid transfer of people with chest pain to hospital, however, unscheduled care pathways vary in their directness (the minimal number of contacts to hospital admission). The aim was to examine unscheduled care pathways and the associations with mortality in people admitted with MI. METHODS: Retrospective population study of all people admitted to Scottish hospitals with a diagnosis of MI between 1 January 2015 and 31 December 2017. Linked data for all National Health Service Scotland unscheduled care services (NHS24 telephone triage service, primary care out of hours, ambulance, emergency department (ED)) was used to define continuous unscheduled care pathways (pathways), which were categorised by initial contact, and whether they were 'direct' (had minimum number of contacts between first contact and admission). Analysis estimated ORs and 95% CIs in adjusted models in which all covariates were included. RESULTS: 26 325 people admitted with MI (63.1% men, 61.6% aged 65+ years), of whom 5.6% died from coronary heart disease within 28 days. For 47.0%, the first unscheduled care contact was ambulance, 23.3% attended ED directly and 18.7% called telephone triage. 92.1% of pathways were direct. Pathways starting with telephone triage were more likely to be indirect compared with other initial contacts (adjusted OR (aOR) 1.97, 95% CI 1.61 to 2.40). Compared to direct pathways, indirect pathways starting with telephone triage were associated with higher mortality (aOR 1.97, 95% CI 1.61 to 2.40) as were indirect pathways starting with another service (aOR 1.55, 95% CI 1.19 to 2.01), but not direct pathways starting with telephone triage (aOR 0.87, 95% CI 0.74 to 1.02). CONCLUSION: Unscheduled care pathways leading to admission with MI in Scotland are usually direct, but those starting with telephone triage were more commonly indirect. Those indirect pathways were associated with higher mortality.

Comparing the longer-term effectiveness of a single dose of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines across the age spectrum.

Background: A single dose strategy may be adequate to confer population level immunity and protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in low- and middle-income countries where vaccine supply remains limited. We compared the effectiveness of a single dose strategy of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines against SARS-CoV-2 infection across all age groups and over an extended follow-up period. Methods: Individuals vaccinated in North-West London, UK, with either the first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines between January 12, 2021 and March 09, 2021, were matched to each other by demographic and clinical characteristics. Each vaccinated individual was additionally matched to an unvaccinated control. Study outcomes included SARS-CoV-2 infection of any severity, COVID-19 hospitalisation, COVID-19 death, and all-cause mortality. Findings: Amongst matched individuals, 63,608 were in each of the vaccine groups and 127,216 were unvaccinated. Between 14 and 84 days of follow-up after matching, there were 534 SARS-CoV-2 infections, 65 COVID-19 hospitalisations, and 190 deaths, of which 29 were categorized as due to COVID-19. The incidence rate ratio (IRR) for SARS-CoV-2 infection was 0.85 (95% confidence interval [CI], 0.69 to 1.05) for Oxford-Astra-Zeneca, and 0.69 (0.55 to 0.86) for Pfizer-BioNTech. The IRR for both vaccines was the same at 0.25 (0.09 to 0.55) and 0.14 (0.02 to 0.58) for reducing COVID-19 hospitalization and COVID-19 mortality, respectively. The IRR for all-cause mortality was 0.25 (0.15 to 0.39) and 0.18 (0.10 to 0.30) for the Oxford-Astra-Zeneca and Pfizer-BioNTech vaccines, respectively. Age was an effect modifier of the association between vaccination and SARS-CoV-2 infection of any severity; lower hazard ratios for increasing age. Interpretation: A single dose strategy, for both vaccines, was effective at reducing COVID-19 mortality and hospitalization rates. The magnitude of vaccine effectiveness was comparatively lower for SARS-CoV-2 infection, although this was variable across the age range, with higher effectiveness seen with older adults. Our results have important implications for health system planning -especially in low resource settings where vaccine supply remains constrained.

Sharing a household with children and risk of COVID-19: a study of over 300 000 adults living in healthcare worker households in Scotland.

OBJECTIVE: Children are relatively protected from COVID-19, due to a range of potential mechanisms. We investigated if contact with children also affords adults a degree of protection from COVID-19. DESIGN: Cohort study based on linked administrative data. SETTING: Scotland. STUDY POPULATION: All National Health Service Scotland healthcare workers and their household contacts as of March 2020. MAIN EXPOSURE: Number of young children (0-11 years) living in the participant's household. MAIN OUTCOMES: COVID-19 requiring hospitalisation, and any COVID-19 (any positive test for SARS-CoV-2) in adults aged ≥18 years between 1 March and 12 October 2020. RESULTS: 241 266, 41 198, 23 783 and 3850 adults shared a household with 0, 1, 2 and 3 or more young children, respectively. Over the study period, the risk of COVID-19 requiring hospitalisation was reduced progressively with increasing numbers of household children-fully adjusted HR (aHR) 0.93 per child (95% CI 0.79 to 1.10). The risk of any COVID-19 was similarly reduced, with the association being statistically significant (aHR per child 0.93; 95% CI 0.88 to 0.98). After schools reopened to all children in August 2020, no association was seen between exposure to young children and risk of any COVID-19 (aHR per child 1.03; 95% CI 0.92 to 1.14). CONCLUSION: Between March and October 2020, living with young children was associated with an attenuated risk of any COVID-19 and COVID-19 requiring hospitalisation among adults living in healthcare worker households. There was no evidence that living with young children increased adults' risk of COVID-19, including during the period after schools reopened.

CardiOvaScular Mechanisms In Covid-19: methodology of a prospective observational multimodality imaging study (COSMIC-19 study).

BACKGROUND: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. METHODS: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA and 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. DISCUSSION: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION: This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at https://www.isrctn.com/ISRCTN12154994.

Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19.

BACKGROUND: Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain. METHODS: In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19. Diagnostic performance of the index and serial tests was evaluated for a primary outcome of confirmed or probable COVID-19, and a secondary outcome of confirmed COVID-19 on serial testing. The diagnosis was adjudicated by a panel, who recorded clinical, laboratory and radiological features blinded to the test results. RESULTS: We enrolled 1368 consecutive patients (median age 68 [interquartile range, IQR 53-80] years, 47% women) who underwent a total of 3822 tests (median 2 [IQR 1-3] tests per patient). The primary outcome occurred in 36% (496/1368), of whom 65% (323/496) and 35% (173/496) had confirmed and probable COVID-19, respectively. The index test was positive in 255/496 (51%) patients with the primary outcome, giving a sensitivity and specificity of 51.4% (95% confidence interval [CI] 48.8 to 54.1%) and 99.5% (95% CI 99.0 to 99.8%). Sensitivity increased in those undergoing 2, 3 or 4 tests to 60.1% (95% CI 56.7 to 63.4%), 68.3% (95% CI 64.0 to 72.3%) and 77.6% (95% CI 72.7 to 81.9%), respectively. The sensitivity of the index test was 78.9% (95% CI 74.4 to 83.2%) for the secondary outcome of confirmed COVID-19 on serial testing. CONCLUSIONS: In patients admitted to hospital, a single combined nasal and throat swab with RT-PCR for SARS-CoV-2 has excellent specificity, but limited diagnostic sensitivity for COVID-19. Diagnostic performance is significantly improved by repeated testing.

Data gaps in electronic health record (EHR) systems: An audit of problem list completeness during the COVID-19 pandemic.

OBJECTIVE: To evaluate the completeness of diagnosis recording in problem lists in a hospital electronic health record (EHR) system during the COVID-19 pandemic. DESIGN: Retrospective chart review with manual review of free text electronic case notes. SETTING: Major teaching hospital trust in London, one year after the launch of a comprehensive EHR system (Epic), during the first peak of the COVID-19 pandemic in the UK. PARTICIPANTS: 516 patients with suspected or confirmed COVID-19. MAIN OUTCOME MEASURES: Percentage of diagnoses already included in the structured problem list. RESULTS: Prior to review, these patients had a combined total of 2841 diagnoses recorded in their EHR problem lists. 1722 additional diagnoses were identified, increasing the mean number of recorded problems per patient from 5.51 to 8.84. The overall percentage of diagnoses originally included in the problem list was 62.3% (2841 / 4563, 95% confidence interval 60.8%, 63.7%). CONCLUSIONS: Diagnoses and other clinical information stored in a structured way in electronic health records is extremely useful for supporting clinical decisions, improving patient care and enabling better research. However, recording of medical diagnoses on the structured problem list for inpatients is incomplete, with almost 40% of important diagnoses mentioned only in the free text notes.

COVID-19 - exploring the implications of long-term condition type and extent of multimorbidity on years of life lost: a modelling study.

Background: COVID-19 is responsible for increasing deaths globally. As most people dying with COVID-19 are older with underlying long-term conditions (LTCs), some speculate that YLL are low. We aim to estimate YLL attributable to COVID-19, before and after adjustment for number/type of LTCs, using the limited data available early in the pandemic. Methods: We first estimated YLL from COVID-19 using WHO life tables, based on published age/sex data from COVID-19 deaths in Italy. We then used aggregate data on number/type of LTCs in a Bayesian model to estimate likely combinations of LTCs among people dying with COVID-19. We used routine UK healthcare data from Scotland and Wales to estimate life expectancy based on age/sex/these combinations of LTCs using Gompertz models from which we then estimate YLL. Results: Using the standard WHO life tables, YLL per COVID-19 death was 14 for men and 12 for women. After adjustment for number and type of LTCs, the mean YLL was slightly lower, but remained high (11.6 and 9.4 years for men and women, respectively). The number and type of LTCs led to wide variability in the estimated YLL at a given age (e.g. at ≥80 years, YLL was >10 years for people with 0 LTCs, and <3 years for people with ≥6). Conclusions: Deaths from COVID-19 represent a substantial burden in terms of per-person YLL, more than a decade, even after adjusting for the typical number and type of LTCs found in people dying of COVID-19. The extent of multimorbidity heavily influences the estimated YLL at a given age. More comprehensive and standardised collection of data (including LTC type, severity, and potential confounders such as socioeconomic-deprivation and care-home status) is needed to optimise YLL estimates for specific populations, and to understand the global burden of COVID-19, and guide policy-making and interventions.

A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.

OBJECTIVES: The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. MATERIALS AND METHODS: We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. RESULTS: We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. DISCUSSION AND CONCLUSION: Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.

AIMS: Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare. METHODS AND RESULTS: We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths. CONCLUSION: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study.

OBJECTIVE: To assess the risk of hospital admission for coronavirus disease 2019 (covid-19) among patient facing and non-patient facing healthcare workers and their household members. DESIGN: Nationwide linkage cohort study. SETTING: Scotland, UK, 1 March to 6 June 2020. PARTICIPANTS: Healthcare workers aged 18-65 years, their households, and other members of the general population. MAIN OUTCOME MEASURE: Admission to hospital with covid-19. RESULTS: The cohort comprised 158 445 healthcare workers, most of them (90 733; 57.3%) being patient facing, and 229 905 household members. Of all hospital admissions for covid-19 in the working age population (18-65 year olds), 17.2% (360/2097) were in healthcare workers or their households. After adjustment for age, sex, ethnicity, socioeconomic deprivation, and comorbidity, the risk of admission due to covid-19 in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazard ratio 0.81 (95% confidence interval 0.52 to 1.26) and 0.86 (0.49 to 1.51), respectively). In models adjusting for the same covariates, however, patient facing healthcare workers, compared with non-patient facing healthcare workers, were at higher risk (hazard ratio 3.30, 2.13 to 5.13), as were household members of patient facing healthcare workers (1.79, 1.10 to 2.91). After sub-division of patient facing healthcare workers into those who worked in "front door," intensive care, and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (hazard ratio 2.09, 1.49 to 2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of hospital admission with covid-19 was less than 0.5%, but it was 1% and above in older men with comorbidity. CONCLUSIONS: Healthcare workers and their households contributed a sixth of covid-19 cases admitted to hospital. Although the absolute risk of admission was low overall, patient facing healthcare workers and their household members had threefold and twofold increased risks of admission with covid-19.

COVID-19 – exploring the implications of long-term condition type and extent of multimorbidity on years of life lost: a modelling study [version 1;peer review: awaiting peer review]

Background: The COVID-19 pandemic is responsible for increasing deaths globally. Most estimates have focused on numbers of deaths, with little direct quantification of years of life lost (YLL) through COVID-19. As most people dying with COVID-19 are older with underlying long-term conditions (LTCs), some have speculated that YLL are low. We aim to estimate YLL attributable to COVID-19, before and after adjustment for number/type of LTCs. Methods: We first estimated YLL from COVID-19 using standard WHO life tables, based on published age/sex data from COVID-19 deaths in Italy. We then used aggregate data on number/type of LTCs to model likely combinations of LTCs among people dying with COVID-19. From these, we used routine UK healthcare data to estimate life expectancy based on age/sex/different combinations of LTCs. We then calculated YLL based on age, sex and type of LTCs and multimorbidity count. Results: Using the standard WHO life tables, YLL per COVID-19 death was 14 for men and 12 for women. After adjustment for number and type of LTCs, the mean YLL was slightly lower, but remained high (13 and 11 years for men and women, respectively). The number and type of LTCs led to wide variability in the estimated YLL at a given age (e.g. at ≥80 years, YLL was 10 years for people with 0 LTCs, and 3 years for people with ≥6). Conclusions: Deaths from COVID-19 represent a substantial burden in terms of per-person YLL, more than a decade, even after adjusting for the typical number and type of LTCs found in people dying of COVID-19. The extent of multimorbidity heavily influences the estimated YLL at a given age. More comprehensive and standardised collection of data on LTCs is needed to better understand and quantify the global burden of COVID-19 and to guide policy-making and interventions.

Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. RESULTS: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. CONCLUSIONS: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.