Dying From COVID-19 or With COVID-19: A Definitive Answer Through a Retrospective Analysis of Mortality in Italy (Preprint)

BACKGROUND COVID-19 mortality was associated with several reasons, including conspiracy theories and infodemic phenomena. However, little is known about the potential endogenous reasons for the increase in COVID-19 associated mortality in Italy. OBJECTIVE This study aimed to search the potential endogenous reasons for the increase in COVID-19 mortality recorded in Italy during the year 2020 and evaluate the statistical significance of the latter. METHODS We analyzed all the trends in the timelapse 2011-2019 related to deaths by age, sex, region, and cause of death in Italy and compared them with those of 2020. Ordinary least squares (OLS) linear regressions and ARIMA (p, d, q) models were applied to investigate the predictions of death in 2020 as compared to death reported in the same year. Grubbs and Iglewicz-Hoaglin tests were used to identify the statistical differences between the predicted and observed deaths. The relationship between mortality and predictive variables was assessed using OLS multiple regression models. RESULTS Both ARIMA and OLS linear regression models predicted the number of deaths in Italy during 2020 to be between 640,000 and 660,000 (95% confidence intervals range: 620,000 – 695,000) and these values were far from the observed deaths reported (above 750,000). Significant difference in deaths at national level (P = 0.003), and higher male mortality than women (+18% versus +14%, P < 0.001 versus P = 0.01) was observed. Finally, higher mortality was strongly and positively correlated with latitude (R = 0.82, P < 0.001). CONCLUSIONS Our findings support the absence of historical endogenous reasons capable of justifying the increase in deaths and mortality observed in Italy in 2020. Together with the current knowledge on the novel coronavirus 2019, these findings provide decisive evidence on the devastating impact of COVID-19 in Italy. We suggest that this research be leveraged by government, health, and information authorities to furnish proof against conspiracy hypotheses. Moreover, given the marked concordance between the predictions of the ARIMA and OLS regression models, we suggest that these models be exploited to predict mortality trends.

Dying from COVID-19 or with COVID-19: a definitive answer through a retrospective analysis of mortality in Italy

Background: COVID-19 mortality was associated with several reasons, including conspiracy theories and infodemic phenomena. However, little is known about the potential endogenous reasons for the increase in COVID-19 associated mortality in Italy. Objective: This study aimed to search the potential endogenous reasons for the increase in COVID-19 mortality recorded in Italy during the year 2020 and evaluate the statistical significance of the latter. Methods: We analyzed all the trends in the timelapse 2011-2019 related to deaths by age, sex, region, and cause of death in Italy and compared them with those of 2020. Ordinary least squares (OLS) linear regressions and ARIMA (p, d, q) models were applied to investigate the predictions of death in the year 2020 as compared to death reported in 2020. Grubbs and Iglewicz-Hoaglin tests were used to identify the statistical differences between the predictors and observed death during the year 2020. The relationship between mortality and predictive variables was assessed using OLS multiple regression models. Results: Both ARIMA and OLS linear regression models predicted the number of deaths in Italy during the year 2020 is between 640,000 and 660,000 (95% confidence intervals range: 620,000 - 695,000) and these values were far from the observed deaths reported (n = 750,000). Significant difference in deaths at national level (P = 0.003), and higher male mortality than women (+18% versus +14%, P < 0.001 versus P = 0.01) was observed. Finally, higher mortality was strongly and positively correlated with latitude (R = 0.82, P < 0.001) Conclusions: Our findings suggest that the absence of historical endogenous reasons capable of justifying the increase in deaths and mortality observed in Italy in 2020. Together with the current knowledge on the novel coronavirus 2019, these findings provide decisive evidence on the devastating impact of COVID-19 in Italy. We suggest that this research be leveraged by government, health, and information authorities to furnish proof against conspiracy theorists. Moreover, given the marked concordance between the predictions of the ARIMA and OLS regression models, we suggest that these models be exploited to predict mortality trends.

Gender differences in life expectancy of the population of Tatarstan

During the spread of coronavirus infection around the world, much attention is being paid to study of excessive mortality of the population, which has impact on life expectancy. Achieving the goals set by the Government of the Russian Federation to achieve life expectancy of 78 years by 2030 depends on many factors, including reduction of gender differences in life expectancy and excess mortality of the male population from various classes of causes. But in 2020 there was a turning point which led to a decrease in life expectancy to the level of 2014. This fact requires a more detailed study of the negative consequences of gender differences in this demographic indicator. The data of Rosstat and the sociological study "Demographic well-being of Tatarstan" conducted by the Family and Demography Center of the Tatarstan Academy of Sciences served as an information resource. The purpose of the article is to identify the main social consequences of gender differences in life expectancy. The main socio-cultural and behavioral factors of male mortality are highlighted. Among the behavioral factors that are closest to explaining the high mortality of Russian men is alcohol consumption, which is considered as an optional phenomenon of suicide. The direct expression (consequence) of a certain behavior is the most characteristic tendency of men to neglect their own health. In order to change the situation, only the state policy on development of measures aimed at creating conditions for raising the life expectancy is not sufficient, it is also necessary to change the consciousness of men to form motivation for the need to preserve and strengthen health.

Trends of HIV-Related Cancer Mortality between 2001 and 2018: An Observational Analysis

The burden of AIDS-defining cancers has remained relatively steady for the past two decades, whilst the burden of non-AIDS-defining cancer has increased. Here, we conduct a study to describe mortality trends attributed to HIV-associated cancers in 31 countries. We extracted HIV-related cancer mortality data from 2001 to 2018 from the World Health Organization Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 population using the World Standard Population. Data were visualized using Locally Weighted Scatterplot Smoothing (LOWESS). Data for females were available for 25 countries. Overall, there has been a decrease in mortality attributed to HIV-associated cancers among most of the countries. In total, 18 out of 31 countries (58.0%) and 14 out of 25 countries (56.0%) showed decreases in male and female mortality, respectively. An increasing mortality trend was observed in many developing countries, such as Malaysia and Thailand, and some developed countries, such as the United Kingdom. Malaysia had the greatest increase in male mortality (+495.0%), and Canada had the greatest decrease (−88.5%). Thailand had the greatest increase in female mortality (+540.0%), and Germany had the greatest decrease (−86.0%). At the endpoint year, South Africa had the highest ASDRs for both males (16.8/100,000) and females (19.2/100,000). The lowest was in Japan for males (0.07/100,000) and Egypt for females (0.028/100,000).

Contribution of the Elevated Thrombosis Risk of Males to the Excess Male Mortality Observed in COVID-19: An Observational Study

Background: The mortality rate of COVID-19 is elevated in males compared to females.Objective: Determine the extent that the elevated thrombotic risk in males relative to females contributes to excess COVID-19 mortality in males.Design: Observational study.Setting: Data sourced from electronic medical records from over 200 US hospital systems.Participants: 60,877 patients hospitalized with COVID-19.Exposure: Exposure variable: biological sex; key variable of interest: thrombosis.Main outcome measures: Primary outcome was COVID-19 mortality. We measured: 1) mortality rate of males relative to females, 2) rate of thrombotic diagnoses occurring during hospitalization for COVID-19 in both sexes, and 3) mortality rate when evidence of thrombosis was present.Results: The COVID-19 mortality rate of males was 29.9% higher than that of females. Males had a 35.8% higher rate of receiving a thrombotic diagnosis compared to females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%— over twice that of COVID-19 patients without a thrombotic diagnosis (adjusted OR 2.50 [2.37 to 2.64], p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or a D-dimer level ≥ 3.0 μg/mL, 16.4% of the excess mortality in male patients could be explained by increased thrombotic risk. Conclusions and Relevance: Our findings suggest the higher COVID-19 mortality rate in males may be significantly accounted for by the elevated risk for thrombosis among males. Understanding the mechanisms that underlie increased male thrombotic risk may allow for the advancement of effective anticoagulation strategies that reduce COVID-19 mortality in males.

560. Evaluation of Optimal Methylprednisolone Dose in Patients with Covid 19

Background Optimal dose of methylprednisolone in patients with moderate or severe COVID-19 is unclear. In our hospital, the use of 250-500 mg/day of methylprednisolone was frequent in the first wave of the pandemic. Lower dose were recommended in our protocol since September 2020. The aim was to evaluate the impact of methylprednisolone dose in the outcome of patients with moderate or severe COVID-19. Methods This is a retrospective and observational study. Inclusion criteria: SARS-CoV-2 infection diagnosed by PCR, admission to our hospital between March 2020 and February 2021, SatO2 &lt; 94% or SatO2/FiO2 &lt; 447. Two treatment groups were compared: patients treated with 0.5-1.5 mg/kg/day (group 1) and patients treated with more than 1.5 mg/kg/day (group 2). The primary outcome analyzed was orotracheal intubation (OTI) or death from any cause at 28 days after admission. Differences in demographic, clinical and laboratory characteristics between treatment groups were analyzed. Variables with P &lt; 0.1 were included in a binary logistic regression model, calculating a propensity score for assigning each patient to group 1 treatment. Bivariate analysis was performed to identify variables associated with worst outcome. Finally, Cox regression was performed including treatment group, propensity score as covariate and all the variables with P&lt; 0.05 in the bivariate analysis. Results 285 patients were included, 197 in group 1 and 88 in group 2. The median age was 73 years, 52,3% were male. Mortality or OTI at 28 days was 24,9%. There was a higher proportion of patients in group 1 with COPD (9,6% vs 1.1%, P&lt; 0.01), dyspnea (60.4% vs 45.5%, P=0.01), sepsis (22.8% vs 13.6%, P=0.07). Patients in group 2 had more impaired consciousness (18.2% vs 8.6%, P=0.02). The median of lymphocytes count was lower in group 1 (900 vs 1025, P=0.01). There were no differences in the primary outcome between treatment groups (26.1% in the group 2 vs 24.4% in the group 1, P=0.7). Conclusion The use of high dose of methylprednisolone compared with intermediate dose is not associated with a better outcome in patients with moderate or severe COVID-19. Disclosures All Authors: No reported disclosures

Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic

Europe experienced excess mortality from February through June, 2020 due to the COVID-19 pandemic, with more COVID-19-associated deaths in males compared to females. However, a difference in excess mortality among females compared to among males may be a more general phenomenon, and should be investigated in none-COVID-19 situations as well. Based on death counts from Eurostat, separate excess mortalities were estimated for each of the sexes using the EuroMOMO model. Sex-differential excess mortality were expressed as differences in excess mortality incidence rates between the sexes. A general relation between sex-differential and overall excess mortality both during the COVID-19 pandemic and in preceding seasons were investigated. Data from 27 European countries were included, covering the seasons 2016/17 to 2019/20. In periods with increased excess mortality, excess was consistently highest among males. From February through May 2020 male excess mortality was 52.7 (95% PI: 56.29; 49.05) deaths per 100,000 person years higher than for females. Increased male excess mortality compared to female was also observed in the seasons 2016/17 to 2018/19. We found a linear relation between sex-differences in excess mortality and overall excess mortality, i.e., 40 additional deaths among males per 100 excess deaths per 100,000 population. This corresponds to an overall female/male mortality incidence ratio of 0.7. In situations with overall excess mortality, excess mortality increases more for males than females. We suggest that the sex-differences observed during the COVID-19 pandemic reflects a general sex-disparity in excess mortality.

The impact of ACE2 genetic polymorphisms (rs2106809 and rs2074192) on gender susceptibility to COVID-19 infection and recovery: A systematic review

Background: Epidemiological studies revealed there is a difference in susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of differences in gender with age and males being more inflicted. There is a clear indication that deaths caused by coronavirus disease 2019 (COVID-19) in males appeared at a higher rate than females across 35 nations. The implication of associated disease-risk genes, involved in the susceptibility of COVID-19 such as the angiotensin-converting enzyme 2 (ACE2), has recently received considerable attention due to their role in severe injury of lung and mediated SARS-CoV-2 entry as a host receptor. Objectives: Herein, we aimed to systematically review how two main genetic polymorphisms of ACE2 (rs2106809 and rs2074192) can affect the gender susceptibility to SARS-CoV-2 infection. Methods: To conduct this systematic review, a literature search in PubMed, Google Scholar, ScienceDirect, and Nature was made for the period 2004 to 2020. We searched for the impact of ACE2 genetic polymorphisms (rs2106809 and rs2074192) on gender susceptibility. Results: We noticed that there was a differential genotype distribution between males and females in various global populations whereas mutant variants were common in males compared to wild-type variants among females, which may reflect differences in gender susceptibility to infection with SARS-CoV-2. Females are less susceptible to coronavirus as compare to males because of the expression of ACE2 receptor. It has a double role in favour of COVID-19 and against COVID-19. Conclusions: Male mortality is greater than female mortality, which might be attributed to the ACE2 deficiency in women. Epidemiological studies have shown that the differences in sex and age have different susceptibility to SARS-CoV-2 infection.

Right ventricular function is associated with 28-day mortality in myocardial infarction complicated by cardiogenic shock: A retrospective observational study

Background Right ventricular (RV) function is increasingly being recognised as an important factor influencing outcomes in ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). In this study, we investigated RV echocardiographic parameters’ association with 28-day mortality in patients admitted to intensive care with STEMI complicated by CS with reduced left ventricle ejection fraction (LVEF). Method We performed a retrospective analysis of patients admitted to intensive care unit (ICU) in a single tertiary cardiac centre over a 34-month period with STEMI complicated by CS and LVEF < 40%. Clinical and echocardiographic data were collected and correlated with 28-day mortality. Results One-hundred patients were included with a mean age of 62.6 ±12.7 years and 78% were male. Mortality at 28 days was 37%. Respectively, 85%, 40% and 25% of patients required mechanical ventilation, mechanical circulatory support and renal replacement therapy. Tricuspid annulus peak systolic velocity (RV S’) was significantly higher in survivors (12 ± 3.3 v 10 ± 3.5 cm/s, p = 0.03) and was an independent predictor of mortality (odds ratio 1.2, 95% confidence interval 1.1–1.4, p = 0.04). RV S’ of 10.5 cm/s exhibited best sensitivity and specificity (64% and 65%, respectively; p = 0.02) for mortality. The Kaplan–Meier curve demonstrated 85% risk of 28-day mortality for RV S’ < 10.5 cm/s v 53% for RV S’ > 10.5 cm/s ( p = 0.02). Conclusion RV function is associated 28-day mortality in patients admitted to ICU with STEMI complicated by CS with reduced LVEF. RV S’ predicted mortality with good sensitivity and specificity.

Modelling Nigeria Male Mortality Using Functional Data Time Series Analysis Approach.

Incidence and mortality rates are considered as a guideline for planning public health strategies and allocating resources. Several methods have been proposed and used for modeling mortalities of various countries. Among the leading mortality, models are the Lee-Carter model which has been used in various countries and adjudged to fit the mortality of these countries well. But it came with its own limitations as the model was used in a more developed nation. In this research work, we propose functional data analysis techniques to model Nigerian Male mortality using the data obtained from the Nigeria Bureau of Statistics from 1998-2010. We compared the results obtained using some parameters such as MAPE and MSE. From the results, we discovered that the improvement of the parameters of our model shows that it is better than the Lee-Carter model in analyzing Nigerian Male Mortality.