Age-adjusted associations between comorbidity and outcomes of COVID-19: a review of the evidence

ABSTRACT Background Current evidence suggests that older people and people with underlying comorbidities are at increased risk of severe disease and death following hospitalisation with COVID-19. As comorbidity increases with age, it is necessary to understand the age-adjusted relationship between comorbidity and COVID-19 outcomes, in order to enhance planning capabilities and our understanding of COVID-19. Methods We conducted a rapid, comprehensive review of the literature up to 10 April 2020, to assess the international empirical evidence on the association between comorbidities and severe or critical care outcomes of COVID-19, after accounting for age, among hospitalised patients with COVID-19. Results After screening 579 studies, we identified seven studies eligible for inclusion and these were synthesised narratively. All were from China. The emerging evidence base mostly indicates that after adjustment for age (and in some cases other potential confounders), obesity, hypertension, diabetes mellitus, chronic obstructive airways disease (COPD), and cancer are all associated with worse outcomes. The largest study, using a large nationwide sample of COVID-19 patients in China, found that those with multiple comorbidities had more than twice the risk of a severe outcome or death compared with patients with no comorbidities, after adjusting for age and smoking (HR=2.59, 95% CI 1.61, 4.17). Conclusions This review summarises for clinicians, policymakers, and academics the most robust evidence to date on this topic, to inform the management of patients and control measures for tackling the pandemic. Given the intersection of comorbidity with ethnicity and social disadvantage, these findings also have important implications for health inequalities. As the pandemic develops, further research should confirm these trends in other settings outside China and explore mechanisms by which various underlying health conditions increase risk of severe COVID-19

Inequalities in COVID19 mortality related to ethnicity and socioeconomic deprivation - pre-print paper

Background: Initial reports suggest that ethnic minorities may be experiencing more severe coronavirus disease 2019 (COVID19) outcomes. We therefore assessed the association between ethnic composition, income deprivation and COVID19 mortality rates in England. Methods: We performed a cross-sectional ecological analysis across England's upper-tier local authorities. We assessed the association between the proportion of the population from Black, Asian and Minority Ethnic (BAME) backgrounds, income deprivation and COVID19 mortality rates using multivariable negative binomial regression, adjusting for population density, proportion of the population aged 50-79 and 80+ years, and the duration of the epidemic in each area. Findings: Local authorities with a greater proportion of residents from ethnic minority backgrounds had statistically significantly higher COVID19 mortality rates, as did local authorities with a greater proportion of residents experiencing deprivation relating to low income. After adjusting for income deprivation and other covariates, each percentage point increase in the proportion of the population from BAME backgrounds was associated with a 1% increase in the COVID19 mortality rate [IRR=1.01, 95%CI 1.01-1.02]. Each percentage point increase in the proportion of the population experiencing income deprivation was associated with a 2% increase in the COVID19 mortality rate [IRR=1.02, 95%CI 1.01-1.04]. Interpretation: This study provides evidence that both income deprivation and ethnicity are associated with greater COVID19 mortality. To reduce these inequalities, Government needs to target effective control and recovery measures at these disadvantaged communities, proportionate to their greater needs and vulnerabilities, during and following the pandemic

Age-Adjusted Associations Between Comorbidity and Outcomes of COVID-19: A Review of the Evidence From the Early Stages of the Pandemic

Objectives: Early in the COVID-19 pandemic, people with underlying comorbidities were overrepresented in hospitalised cases of COVID-19, but the relationship between comorbidity and COVID-19 outcomes was complicated by potential confounding by age. This review therefore sought to characterise the international evidence base available in the early stages of the pandemic on the association between comorbidities and progression to severe disease, critical care, or death, after accounting for age, among hospitalised patients with COVID-19.Methods: We conducted a rapid, comprehensive review of the literature (to 14 May 2020), to assess the international evidence on the age-adjusted association between comorbidities and severe COVID-19 progression or death, among hospitalised COVID-19 patients – the only population for whom studies were available at that time.Results: After screening 1,100 studies, we identified 14 eligible for inclusion. Overall, evidence for obesity and cancer increasing risk of severe disease or death was most consistent. Most studies found that having at least one of obesity, diabetes mellitus, hypertension, heart disease, cancer, or chronic lung disease was significantly associated with worse outcomes following hospitalisation. Associations were more consistent for mortality than other outcomes. Increasing numbers of comorbidities and obesity both showed a dose-response relationship. Quality and reporting were suboptimal in these rapidly conducted studies, and there was a clear need for additional studies using population-based samples.Conclusions: This review summarises the most robust evidence on this topic that was available in the first few months of the pandemic. It was clear at this early stage that COVID-19 would go on to exacerbate existing health inequalities unless actions were taken to reduce pre-existing vulnerabilities and target control measures to protect groups with chronic health conditions.</jats:p

T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes

Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response. Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10–15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events. Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function

Mediators of socioeconomic inequalities in preterm birth: a systematic review.

BackgroundRates of preterm birth are substantial with significant inequalities. Understanding the role of risk factors on the pathway from maternal socioeconomic status (SES) to preterm birth can help inform interventions and policy. This study therefore aimed to identify mediators of the relationship between maternal SES and preterm birth, assess the strength of evidence, and evaluate the quality of methods used to assess mediation.MethodsUsing Scopus, Medline OVID, "Medline In Process & Other Non-Indexed Citation", PsycINFO, and Social Science Citation Index (via Web of Science), search terms combined variations on mediation, socioeconomic status, and preterm birth. Citation and advanced Google searches supplemented this. Inclusion criteria guided screening and selection of observational studies Jan-2000 to July-2020. The metric extracted was the proportion of socioeconomic inequality in preterm birth explained by each mediator (e.g. 'proportion eliminated'). Included studies were narratively synthesised.ResultsOf 22 studies included, over one-half used cohort design. Most studies had potential measurement bias for mediators, and only two studies fully adjusted for key confounders. Eighteen studies found significant socioeconomic inequalities in preterm birth. Studies assessed six groups of potential mediators: maternal smoking; maternal mental health; maternal physical health (including body mass index (BMI)); maternal lifestyle (including alcohol consumption); healthcare; and working and environmental conditions. There was high confidence of smoking during pregnancy (most frequently examined mediator) and maternal physical health mediating inequalities in preterm birth. Significant residual inequalities frequently remained. Difference-of-coefficients between models was the most common mediation analysis approach, only six studies assessed exposure-mediator interaction, and only two considered causal assumptions.ConclusionsThe substantial socioeconomic inequalities in preterm birth are only partly explained by six groups of mediators that have been studied, particularly maternal smoking in pregnancy. There is, however, a large residual direct effect of SES evident in most studies. Despite the mediation analysis approaches used limiting our ability to make causal inference, these findings highlight potential ways of intervening to reduce such inequalities. A focus on modifiable socioeconomic determinants, such as reducing poverty and educational inequality, is probably necessary to address inequalities in preterm birth, alongside action on mediating pathways

Analysis of the burden and economic impact of digestive diseases and investigation of research gaps and priorities in the field of digestive health in the European Region-White Book 2: Executive summary.

Despite their substantial burden, many digestive diseases are poorly understood, attracting relatively little attention in terms of policy, funding or research. United European Gastroenterology (UEG) commissioned the first White Book, published in 2014, which revealed important insights regarding the public health and economic burden of digestive disorders and health services across Europe. In order to evaluate the current status, increase political and public awareness of digestive disorders and encourage digestive health research, UEG commissioned the White Book 2