Sex Differences in Mortality Rates and Underlying Conditions for COVID-19 Deaths in England and Wales

Mohamed, Mohamed; Gale, Chris P; Kontopantelis, Evangelos; Doran, Tim; Belder, Mark de; Asaria, Miqdad; Lüscher, Thomas F.; Wu, Jianhua; Rashid, Muhammad; Stephenson, Courtney D.; Denwood, Tom; Roebuck, Chris; Deanfield, John; Mamas, Mamas A.

doi:10.1016/j.mayocp.2020.07.009

Cited by 36 publications

(39 citation statements)

References 27 publications

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“…To our knowledge, this is one of the first studies to investigate sex differences in COVID-19 in important CV outcomes and the degree of systemic inflammation after adjustment for comorbidities [ 6 , 13 ]. These findings support differences in sex-specific responses, but suggest that these differences are likely independent of common cardiovascular comorbidities, as has previously been advocated but not well studied [ 8 , 14 , 15 ].…”

Section: Discussionsupporting

confidence: 85%

“…Men have consistently higher unadjusted and adjusted mortality from COVID-19 compared to women as reported by various international agencies and prior literature [ [3] , [4] , [5] , [6] ]. This sex difference in mortality may be related to greater underlying comorbidities in men compared to women, such as hypertension and CVD, which have been linked to increased severity of COVID-19 [ 5 , 7 , 8 ]. In addition, two factors that may contribute to mortality in COVID-19 include myocardial injury defined by troponin elevation, and increased systemic inflammation, both independently associated with in-hospital mortality [ 1 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19

Minhas

Shade

Cho

et al. 2021

International Journal of Cardiology

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Objective Higher mortality in COVID-19 in men compared to women is recognized, but sex differences in cardiovascular events are less well established. We aimed to determine the independent contribution of sex to stroke, myocardial infarction and death in the setting of COVID-19 infection. Methods We performed a retrospective cohort study of hospitalized COVID-19 patients in a racially/ethnically diverse population. Clinical features, laboratory markers and clinical events were initially abstracted from medical records, with subsequent clinician adjudication. Results Of 2060 patients, myocardial injury (32% vs 23%, p = 0.019), acute myocardial infarction (2.7% vs 1.6%, p = 0.114), and ischemic stroke (1.8% vs 0.7%, p = 0.007) were more common in men vs women. In-hospital death occurred in 160 men (15%) vs 117 women (12%, p = 0.091). Men had higher odds of myocardial injury (odds ratio (OR) 2.04 [95%CI 1.43–2.91], p < 0.001), myocardial infarction (1.72 [95%CI 0.93–3.20], p = 0.085) and ischemic stroke (2.76 [95%CI 1.29–5.92], p = 0.009). Despite adjustment for demographics and cardiovascular risk factors, male sex predicted mortality (HR 1.33; 95% CI:1.01–1.74; p = 0.041). While men had significantly higher markers of inflammation, in sex-stratified analyses, increase in interleukin-6, C-reactive protein, ferritin and d-dimer were predictive of mortality and myocardial injury similarly in both sexes. Conclusions Adjusted odds of myocardial injury, ischemic stroke and all-cause mortality, but not myocardial infarction, are significantly higher in men. Higher inflammatory markers are present in men but associated similarly with risk in both men and women. These data suggest that adverse cardiovascular outcomes in men vs. women are independent of cardiovascular comorbidities.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19

Minhas

Shade

Cho

et al. 2021

International Journal of Cardiology

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“…Any additional delays due to the backlog will lead to increased mortality. Of course, these are approximate figures and does not account for excess mortality due to COVID-19 [37].…”

Section: Discussionmentioning

confidence: 99%

Indirect Impact of the COVID-19 Pandemic on Activity and Outcomes of Transcatheter and Surgical Treatment of Severe Aortic Stenosis in England

Martin

Curzen

Goodwin

et al. 2020

Preprint

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Background Aortic stenosis requires timely treatment with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). This study aimed to investigate the indirect impact of COVID-19 on national SAVR and TAVR activity and outcomes. Methods The UK TAVR Registry and the National Adult Cardiac Surgery Audit were used to identify all TAVR and SAVR procedures in England, between January 2017 and June 2020. The number of isolated AVR, AVR+coronary artery bypass graft (CABG) surgery, AVR+other surgery and TAVR procedures per month was calculated. Separate negative binomial regression models were fit to monthly procedural counts, with functions of time as covariates, to estimate the expected change in activity during COVID-19. Results We included 13376 TAVR cases, 12328 isolated AVR cases, 7829 AVR+CABG cases, and 6014 AVR+Other cases. Prior to March 2020 (UK lockdown), monthly TAVR activity was rising, with a slight decrease in SAVR activity during 2019. We observed a rapid and significant drop in TAVR and SAVR activity during the COVID-19 pandemic, especially for elective cases. Cumulatively, over the period March to June 2020, we estimated an expected 2294 (95% CI 1872, 2716) cases of severe aortic stenosis who have not received treatment. Conclusion This study has demonstrated a significant decrease in TAVR and SAVR activity in England following the COVID-19 outbreak. This situation should be monitored closely, to ensure that monthly activity rapidly returns to expected levels. There is potential for significant backlog in the near-to-medium term, and potential for increased mortality in this population.

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“…Similar studies in other countries have reported that COVID-19 was a very significant cause of death in Europe during the first wave of the pandemic, e.g., in England, data from the Office for National Statistics showed that COVID-19 was to blame for one-quarter of all deaths in April 2020 ( n = 33,841, 26.7% of the total deaths) 1 ( 5 ), and the role of comorbidities was also explored in the UK data ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates

et al. 2021

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Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death.Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death.Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February–April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May–September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February–April 2020 and 63.7% in May–September 2020).Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May–September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.

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Sex Differences in Mortality Rates and Underlying Conditions for COVID-19 Deaths in England and Wales

Cited by 36 publications

References 27 publications

The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19

The role of sex and inflammation in cardiovascular outcomes and mortality in COVID-19

Indirect Impact of the COVID-19 Pandemic on Activity and Outcomes of Transcatheter and Surgical Treatment of Severe Aortic Stenosis in England

Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates

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