Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K.

Funder: National Institute for Health Research; Grant(s): Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014), NIHR Applied Research Collaboration East Midlands (ARC EM), NIHR Leicester Biomedical Research CentreBackgroundPre-existing comorbidities have been linked to SARS-CoV-2 infection but evidence is sparse on the importance and pattern of multimorbidity (2 or more conditions) and severity of infection indicated by hospitalisation or mortality. We aimed to use a multimorbidity index developed specifically for COVID-19 to investigate the association between multimorbidity and risk of severe SARS-CoV-2 infection.MethodsWe used data from the UK Biobank linked to laboratory confirmed test results for SARS-CoV-2 infection and mortality data from Public Health England between March 16 and July 26, 2020. By reviewing the current literature on COVID-19 we derived a multimorbidity index including: (1) angina; (2) asthma; (3) atrial fibrillation; (4) cancer; (5) chronic kidney disease; (6) chronic obstructive pulmonary disease; (7) diabetes mellitus; (8) heart failure; (9) hypertension; (10) myocardial infarction; (11) peripheral vascular disease; (12) stroke. Adjusted logistic regression models were used to assess the association between multimorbidity and risk of severe SARS-CoV-2 infection (hospitalisation/death). Potential effect modifiers of the association were assessed: age, sex, ethnicity, deprivation, smoking status, body mass index, air pollution, 25-hydroxyvitamin D, cardiorespiratory fitness, high sensitivity C-reactive protein.ResultsAmong 360,283 participants, the median age was 68 [range 48-85] years, most were White (94.5%), and 1706 had severe SARS-CoV-2 infection. The prevalence of multimorbidity was more than double in those with severe SARS-CoV-2 infection (25%) compared to those without (11%), and clusters of several multimorbidities were more common in those with severe SARS-CoV-2 infection. The most common clusters with severe SARS-CoV-2 infection were stroke with hypertension (79% of those with stroke had hypertension); diabetes and hypertension (72%); and chronic kidney disease and hypertension (68%). Multimorbidity was independently associated with a greater risk of severe SARS-CoV-2 infection (adjusted odds ratio 1.91 [95% confidence interval 1.70, 2.15] compared to no multimorbidity). The risk remained consistent across potential effect modifiers, except for greater risk among older age. The highest risk of severe infection was strongly evidenced in those with CKD and diabetes (4.93 [95% CI 3.36, 7.22]).ConclusionThe multimorbidity index may help identify individuals at higher risk for severe COVID-19 outcomes and provide guidance for tailoring effective treatment

Self-reported walking pace and 10-year cause-specific mortality:A UK biobank investigation

Objective: To investigate associations of self-reported walking pace (SRWP) with relative and absolute risks of cause-specific mortality. Patients and methods: In 391,652 UK Biobank participants recruited in 2006–2010, we estimated sex- and cause-specific (cardiovascular disease [CVD], cancer, other causes) mortality hazard ratios (HRs) and 10-year mortality risks across categories of SRWP (slow, average, brisk), accounting for confounders and competing risk. Censoring occurred in September 30, 2021 (England, Wales) and October 31, 2021 (Scotland). Results: Over a median follow-up of 12.6 years, 22,413 deaths occurred. In women, the HRs comparing brisk to slow SRWP were 0.74 (95% CI: 0.67, 0.82), 0.40 (0.33, 0.49), and 0.29 (0.26, 0.32) for cancer, CVD, and other causes of death, respectively, and 0.71 (0.64, 0.78), 0.38 (0.33, 0.44), and 0.29 (0.26, 0.32) in men. Compared to CVD, HRs were greater for other causes (women: 39.6% [6.2, 72.9]; men: 31.6% [9.8, 53.5]) and smaller for cancer (−45.8% [−58.3, −33.2] and − 45.9% [−54.8, −36.9], respectively). For all causes in both sexes, the 10-year mortality risk was higher in slow walkers, but varied across sex, age, and cause, resulting in different risk reductions comparing brisk to slow: the largest were for other causes of death at age 75 years [women: −6.8% (−7.7, −5.8); men: −9.5% (−10.6, −8.4)]. Conclusion: Compared to slow walkers, brisk SRWP was associated with reduced cancer (smallest reduction), CVD, and other (largest) causes of death and may therefore be a useful clinical predictive marker. As absolute risk reductions varied across age, cause, and SRWP, certain groups may particularly benefit from interventions to increase SRWP.</p

Association Between Accelerometer-Assessed Physical Activity and Severity of COVID-19 in UK Biobank.

Funder: UKRI Science and Technology Facilities CouncilOBJECTIVE: To quantify the association between accelerometer-assessed physical activity and coronavirus disease 2019 (COVID-19) outcomes. METHODS: Data from 82,253 UK Biobank participants with accelerometer data (measured 2013-2015), complete covariate data, and linked COVID-19 data from March 16, 2020, to March 16, 2021, were included. Two outcomes were investigated: severe COVID-19 (positive test result from in-hospital setting or COVID-19 as primary cause of death) and nonsevere COVID-19 (positive test result from community setting). Logistic regressions were used to assess associations with moderate to vigorous physical activity (MVPA), total activity, and intensity gradient. A higher intensity gradient indicates a higher proportion of vigorous activity. RESULTS: Average MVPA was 48.1 (32.7) min/d. Physical activity was associated with lower odds of severe COVID-19 (adjusted odds ratio per standard deviation increase: MVPA, 0.75 [95% CI, 0.67 to 0.85]; total, 0.83 [0.74 to 0.92]; intensity, 0.77 [0.70 to 0.86]), with stronger associations in women (MVPA, 0.63 [0.52 to 0.77]; total, 0.76 [0.64 to 0.90]; intensity, 0.63 [0.53 to 0.74]) than in men (MVPA, 0.84 [0.73 to 0.97]; total, 0.88 [0.77 to 1.01]; intensity, 0.88 [0.77 to 1.00]). In contrast, when mutually adjusted, total activity was associated with higher odds of a nonsevere infection (1.10 [1.04 to 1.16]), whereas the intensity gradient was associated with lower odds (0.91 [0.86 to 0.97]). CONCLUSION: Odds of severe COVID-19 were approximately 25% lower per standard deviation (∼30 min/d) MVPA. A greater proportion of vigorous activity was associated with lower odds of severe and nonsevere infections. The association between total activity and higher odds of a nonsevere infection may be through greater community engagement and thus more exposure to the virus. Results support calls for public health messaging highlighting the potential of MVPA for reducing the odds of severe COVID-19

Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom

OBJECTIVES: To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation. DESIGN: We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID. SETTING: Community-based survey in the UK. PARTICIPANTS: A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation. RESULTS: Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51). CONCLUSIONS: This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

OBJECTIVE: To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications. RESEARCH DESIGN AND METHODS: In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors. RESULTS: Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication. CONCLUSIONS: Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Association between household size and COVID-19: A UK Biobank observational study.

OBJECTIVE: To assess the association between household size and risk of non-severe or severe COVID-19. DESIGN: A longitudinal observational study. SETTING: This study utilised UK Biobank linked to national SARS-CoV-2 laboratory test data. PARTICIPANTS: 401,910 individuals with available data on household size in UK Biobank. MAIN OUTCOME MEASURES: Household size was categorised as single occupancy, two-person households and households of three or more. Severe COVID-19 was defined as a positive SARS-CoV-2 test on hospital admission or death with COVID-19 recorded as the underlying cause; and non-severe COVID-19 as a positive test from a community setting. Logistic regression models were fitted to assess associations, adjusting for potential confounders. RESULTS: Of 401,910 individuals, 3612 (1%) were identified as having suffered from a severe COVID-19 infection and 11,264 (2.8%) from a non-severe infection, between 16 March 2020 and 16 March 2021. Overall, the odds of severe COVID-19 was significantly higher among individuals living alone (adjusted odds ratio: 1.24 [95% confidence interval: 1.14 to 1.36], or living in a household of three or more individuals (adjusted odds ratio: 1.28 [1.17 to 1.39], when compared to individuals living in a household of two. For non-severe COVID-19 infection, individuals living in a single-occupancy household had lower odds compared to those living in a household of two (adjusted odds ratio: 0.88 [0.82 to 0.93]. CONCLUSIONS: Odds of severe or non-severe COVID-19 infection were associated with household size. Increasing understanding of why certain households are more at risk is important for limiting spread of the infection

Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19

ObjectiveTo investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.Research design and methodsIn this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.ResultsCardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age ConclusionsIncreased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes

Healthy lifestyle choices and microvascular complications: New insights into diabetes management

Yogini Chudasama and Kamlesh Khunti discuss new evidence, published in PLOS Medicine, highlighting the importance of healthy lifestyle behaviours in diabetes management

Healthy lifestyle choices and microvascular complications: New insights into diabetes management.

Yogini Chudasama and Kamlesh Khunti discuss new evidence, published in PLOS Medicine, highlighting the importance of healthy lifestyle behaviours in diabetes management

Response to letter to the editor by Abhipsha Sur Roy and Amol Joshi regarding the article: ‘Multimorbidity and SARS-CoV-2 infection in UK Biobank’ (Chudasama et al.)

Letter to the Editor: Response to letter to the editor by Abhipsha Sur Roy and Amol Joshi regarding the article: ‘Multimorbidity and SARS-CoV-2 infection in UK Biobank’ (Chudasama et al.