Sex differences in hepatitis A incidence rates-a multi-year pooled-analysis based on national data from nine high-income countries.

BACKGROUND: Possible sex differences in hepatitis A virus (HAV) incidence rates in different age groups are not well documented. We aimed to obtain stable pooled estimates of such differences based on data from a number of high-income countries. METHODS: We obtained data on incident cases of HAV by sex and age group over a period of 6-25 years from nine countries: Australia, Canada, Czech Republic, Finland, Germany, Israel, Netherland, New Zealand and Spain. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to estimate the effects of age, country, and time period on the IRR. RESULTS: A male excess in incidence rates was consistently observed in all age groups, although in the youngest and oldest age groups, where the numbers tended to be lower, the lower bounds of the 95% confidence intervals for the IRRs were less than one. In the age groups <1, 1-4, 5-9, 10-14, 15-44, 45-64 and 65+, the pooled IRRs (with 95% CI) over countries and time periods were 1.18 (0.94,1.48), 1.22 (1.16,1.29), 1.07 (1.03,1.11), 1.09 (1.04,1.14), 1.46 (1.30,1.64), 1.32 (1.15,1.51) and 1.10 (0.99,1.23) respectively. CONCLUSIONS: The excess HAV incidence rates in young males, pooled over a number of countries, suggest that the sex differences are likely to be due at least in part to physiological and biological differences and not just behavioral factors. At older ages, differential exposure plays an important role. These findings, seen in the context of the excess incidence rates in young males for many other infectious diseases, can provide further keys to the mechanisms of the infection.

Corrigendum: Gender differences in tuberculosis incidence rates-A pooled analysis of data from seven high-income countries by age group and time period.

[This corrects the article DOI: 10.3389/fpubh.2022.997025.].

Predictors of mortality in COVID-19 patients treated with convalescent plasma therapy.

Several options to treat hospitalized severe COVID-19 patients have been suggested. The study aimed to describe survival in patients treated with convalescent COVID plasma (CCP) and to identify in-hospital mortality predictors. This prospective cohort study examined data from 112 severe COVID-19 patients hospitalized in the Corona Departments in an acute care hospital who received two units of CCP (at least one of them high-titer). Demographic and medical data was retrieved from the patients' electronic health records (EHR). Possible predictors for in-hospital mortality were analyzed in a univariate analysis and those found to be clinically significant were further analyzed in a multivariable analysis. Median age was 67 years (IQR 55-74) and 66 (58.9%) of them were males. Of them, 20 (17.9%) died in hospital. On multivariable analysis diabetes mellitus (p = 0.004, OR 91.54), mechanical ventilation (p = 0.001, OR 59.07) and lower albumin levels at treatment (p = 0.027, OR 0.74) were significantly associated with increased in-hospital mortality. In our study, in-hospital mortality in patients receiving CCP is similar to that reported for the general population, however certain variables mentioned above were associated with increased in-hospital mortality. In the literature, these variables were also associated with a worse outcome in patients with COVID-19 who did not receive CCP. As evidence points toward a benefit from CCP treatment in immunocompromised patients, we believe the above risk factors can further define COVID-19 patients at increased risk for mortality, enabling the selection of candidates for early treatment in an outpatient setting if possible.

Gender differences in measles incidence rates in a multi-year, pooled analysis, based on national data from seven high income countries.

BACKGROUND: Gender differences in a number of infectious diseases have been reported. The evidence for gender differences in clinical measles incidence rates has been variable and poorly documented over age groups, countries and time periods. METHODS: We obtained data on cases of measles by sex and age group over a period of 11-27 years from seven countries. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, and 45-64 the pooled IRRs (with 95% CI) were 1.07 (1.02-1.11), 1.10 (1.07-1.14), 1.03 (1.00-1.05), 1.05 (0.99-1.11), 1.08 (0.95-1.23), and 0.82 (0.74-0.92) respectively. The excess incidence rates (IR) from measles in males up to age 45 are remarkably consistent across countries and time-periods. In the age group 45-64, there is an excess incidence in women. CONCLUSIONS: The consistency of the excess incidence rates in young males suggest that the sex differences are more likely due to physiological and biological differences and not behavioral factors. At older ages, differential exposure can play a part. These findings can provide further keys to the understanding of mechanisms of infection and tailoring vaccination schedules.

A Pooled Analysis of Sex Differences in Rotaviral Enteritis Incidence Rates in Three Countries Over Different Time Periods.

Background: Sex differences in incidence rates (IRs) of infectious diseases could provide clues to the mechanisms of infection. The results of studies on sex differences in the incidence of rotaviral enteritis have been inconsistent. Methods: We carried out a pooled analysis of sex differences in IRs for rotaviral enteritis in three countries for a period of 7-22 years. Male-to-female incidence rate ratios (IRRs) were computed by age group, country, and years of reporting. A meta-analytic methodology was used to combine IRRs. Metaregression was performed to evaluate the contribution of age group, country, and years of reporting to the IRR. Results: Significantly higher IRs in males were found in the age groups 0-4, 5-9, and 10-14 years, with pooled IRRs (with 95% confidence intervals [CIs]) of 1.12 (1.09-1.14), 1.07 (1.05-1.09), and 1.13 (1.05-1.21), respectively. In adults, the sex differences were reversed with higher rates in females. The pooled male-to-female IRRs (with 95% CIs) were 0.66 (0.64-0.68), 0.78 (0.72-0.85), and 0.78 (0.72-0.84) for the age groups 15-44, 45-64, and 65+ years, respectively. Metaregression results demonstrated that age is responsible for much of the variation in IRRs. Conclusions: The higher rotaviral enteritis IRs in males at a very early age suggest that sex-related factors unrelated to exposure may play a role. The higher IRs in adult females could result, at least partly, from behavioral and occupational factors.

Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine.

Background: The adverse events reported from the COVID-19 mRNA vaccines have varied from very mild, such as pain near the vaccination site, to more severe, with occasional anaphylaxis. Details of age-specific gender differences for the adverse effects are not well documented. Methods: Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20-65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules.

Gender differences in tuberculosis incidence rates-A pooled analysis of data from seven high-income countries by age group and time period.

Introduction: Gender differences in the incidence rates for tuberculosis are occasionally reported. However, the magnitude and consistency of the differences by age group, among different populations, and over extended periods of time are not clear. Materials and methods: We obtained national data from seven countries from open-access internet sites or personal communications with official representatives. We computed the male-to-female incidence rate ratios (IRRs) by country and year for every age group and pooled these ratios using meta-analytic methods. Meta-regression analysis was performed to estimate the contribution of age, country, and calendar years to the variation in the IRRs. Results: In the age groups of < 1, 1-4, 5-9, and 10-14, the pooled male-to-female IRRs (with 95% CI) were as follows: 1.21 (1.05, 1.40), 0.99 (0.95, 1.04), 1.01 (0.96, 1.06), and 0.83 (0.77, 0.89), respectively. In the age groups 15-44, 45-64, and 65+ years, incidence rates were significantly higher in men, with IRRs of 1.25 (1.16, 1.35), 1.79 (1.56, 2.06), and 1.81 (1.66, 1.96), respectively. Meta-regression analysis revealed that age significantly contributed to the variation in the IRRs. Conclusions: There were gender differences in the incidence rates for tuberculosis, with higher rates in boys aged less than one, no significant differences in boys of ages 1-9, and higher rates in boys/men older than 15. The only excess in female gender was in the age group 10-14 years. The age-related gender differences in tuberculosis incidence rates observed over several countries indicate the importance of including sex as a biological variable when assessing the risk factors for tuberculosis.

Sex Differences in Salmonellosis Incidence Rates-An Eight-Country National Data-Pooled Analysis.

BACKGROUND: There are few studies on sex differences in the incidence rates (IR) for salmonellosis over several countries by age and time period. The purpose of this study was to explore the extent and consistency of the sex and age-specific differences. METHODS: We analyzed national data from eight countries between 1994 and 2016. We computed country-specific male to female incidence rate ratios (IRRs) for each age group and pooled the data using meta-analytic methods. Variations of the IRRs by age, country and time period were evaluated using meta-regression. RESULTS: The pooled male to female incidence RRs for ages 0-1, 1-4, 5-9 and 10-14, were 1.04 (1.02-1.06), 1.02 (1.01-1.03), 1.07 (1.05-1.08) and 1.28 (1.23-1.33), respectively. For the ages 15-44 and 45-64, the incidence rates were significantly higher in females. Meta-regression analyses indicate that age groups contributed most of the variation in the male to female IRRs. CONCLUSIONS: We suggest that genetic and hormonal factors and interactions between hormones and gut microbiota could contribute to the sex differences observed in young children. These findings should provide clues about the mechanisms of the infection, and should be useful in targeting treatments and development of vaccines. HIGHLIGHTS: (1) This manuscript provides consistent estimates of the excess salmonellosis incidence rates in male children up to age 15, which suggests an impact of sex hormones or genetic differences. (2) Our findings should promote the further investigations on sex-related determinants of infectious diseases.

Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women-The Role of Sex Hormones.

Pertussis containing vaccine is recommended for pregnant women to protect neonates prior to being fully immunized against the disease. The immune response during pregnancy may be impacted by changes in the hormonal status. The aim of this study was to evaluate the immune response to pertussis immunization in pregnancy and to assess the role of sex hormones. In a cross-sectional study, blood samples were drawn from 174 pregnant and 74 non-pregnant women 45-60 days following immunization. Anti-pertussis toxin (Anti-PT) IgG antibody levels, estrogen, and progestogen concentrations were compared between the two groups. Multiple logistic regression analysis was used to examine the association between serum antibody and sex hormone concentrations in each group, controlling for age, body mass index (BMI), and smoking status. The geometric mean concentration (GMC) of anti-PT IgG antibody was significantly higher in non-pregnant women compared with pregnant women (median of 2.09 and 1.86, interquartile range = 2.36-1.8 and 2.11-1.16 respectively, p < 0.0001). Among pregnant women, the anti-PT IgG antibody GMC was negatively associated with both progesterone (odds ratio = 0.300, 95% CI = 0.116, 0.772, p = 0.013) and estrogen (odds ratio = 0.071, 95% CI = 0.017, 0.292, p < 0.0001), after controlling for age, BMI, and smoking. Pregnancy was associated with lower anti-PT IgG antibody levels (odds ratio = 0.413, 95% CI = -0.190, 0.899, p = 0.026). This appears to be at least partially explained by the higher levels of hormones during pregnancy. These findings demonstrate the important role of sex hormones in the response to pertussis vaccine during pregnancy and can help to evaluate the optimum vaccination schedule.

Hematological Biomarkers, Mortality, Transfusion and Acute Heart Disease.

BACKGROUND: Patients hospitalized with acute heart disease [acute myocardial infarction (MI); heart disease exacerbation] may require red blood cell (RBC) transfusion. These patients are at increased risk for morbidity and mortality. Hematological biomarkers may help to identify increased mortality risk. The aim of the study was to evaluate the association between hematological biomarkers and survival in these patients. METHODS: A historical cohort study of all patients admitted to an internal medicine department, who were diagnosed with acute heart disease and requiring RBC transfusion, was carried out in a tertiary medical center between 2009-2014. The association between hematological biomarkers and 30-, 90-day and 5-year mortality was studied. RESULTS: A total of 254 patients (median age 80 years, IQR 74-86.25; 40.9% females; acute MI 24.8%), were included. During the 5-year follow-up 212(83.5%) patients died. In a multivariate analysis the lower platelet to neutrophil ratio (PNR) was significantly associated with increased 30-, 90-day and 5-year mortality (p<0.001, 0.041, 0.003 respectively). A higher red cell distribution width (RDW) was significantly associated with 30- and 90-day mortality (p=0.003, 0.023 respectively), while higher neutrophil to lymphocyte ratio (NLR) was associated with increased 30-day and 5-year mortality (p= 0.036, 0.033 respectively). CONCLUSIONS: Hematological biomarkers may help to identify increased mortality risk of acute heart disease patients, receiving RBC transfusions in an internal medicine department.

Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries.

BACKGROUND: Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. METHODS: Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. RESULTS: The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. CONCLUSIONS: The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.

A meta-analytic evaluation of sex differences in meningococcal disease incidence rates in 10 countries.

The magnitude and consistency of the sex differences in meningococcal disease incidence rates (IR) have not been systematically examined in different age groups, countries and time periods. We obtained national data on meningococcal disease IR by sex, age group and time period, from 10 countries. We used meta-analytic methods to combine the male to female incidence rate ratios (IRRs) by country and year for each age group. Meta-regression analysis was used to assess the contribution of age, country and time period to the variation in the IRRs. The pooled male to female IRRs (with 95% CI) for ages 0-1, 1-4, 5-9, 10-14 and 15-44, were 1.25 (1.19-1.32), 1.24 (1.20-1.29), 1.13 (1.07-1.20), 1.21 (1.13-1.29) and 1.15 (1.10-1.21), respectively. In the age groups 45-64 and over 65, the IR were lower in males with IRRs of 0.83 (0.78-0.88) and 0.64 (0.60-0.69), respectively. Sensitivity analysis and meta-regression confirmed that the results were robust. The excess meningococcal IR in young males and the higher rates in females at older ages were consistent in all countries, except the Czech Republic. While behavioural factors could explain some of the sex differences in the older age groups, the excess rates in very young males suggest that genetic and hormonal differences could be important.

The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal-a comparison of age-specific and age-adjusted CFRs between seven countries.

BACKGROUND: Crude case-fatality rates (CFRs) for COVID-19 vary widely between countries. There are serious limitations in the CFRs when making comparisons. We examined how the age distribution of the cases is responsible for the COVID-19 CFR differences between countries. METHODS: COVID-19 cases and deaths, by ten-year age-groups, were available from the reports of seven countries. The overall and age-specific CFRs were computed for each country. The age-adjusted CFRs were computed by the direct method, using the combined number of cases in all seven countries in each age group as the standard population. A meta-analytic approach was used to obtain pooled age-specific CFRs. FINDINGS: The crude overall CFRs varied between 0.82% and 14.2% in the seven countries and the variation in the age-specific CFRs were much smaller. There was wide variation in the age distribution of the cases between countries. The ratio of the crude CFR for the country with the highest CFR to that with the lowest (6.28) was much lower for the age-adjusted CFRs rates (2.57). CONCLUSIONS: The age structure of the cases explains much of differences in the crude CFRs between countries and adjusting for age substantially reduces this variation. Other factors such as the definition of cases, coding of deaths and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. At the very least, age-specific and age-adjusted CFRs should be used for comparisons.

Sex differences in campylobacteriosis incidence rates at different ages - a seven country, multi-year, meta-analysis. A potential mechanism for the infection.

BACKGROUND: There is evidence that males have higher incidence rates (IR) of campylobacteriois than females. The objectives of this study were to determine whether these observations differ between age groups and are consistent over different countries and during different time periods. METHODS: We obtained data on IRs of campylobacteriosis by sex and age group over a period of 11-26 years from seven countries. Male to female incidence rate ratios (IRR) were computed by age group, country and time period. For each age group, we used meta-analytic methods to combine the IRRs. Sensitivity analysis was used to test whether the results are robust to differences between countries and time periods. Meta-regression was conducted to estimate the different effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, 45-64 and 65+ years old, the pooled IRRs (with 95% CI) were 1.31 (1.26-1.37), 1.34 (1.31-1.37), 1.35 (1.32-1.38), 1.73 (1.68-1.79), 1.10 (1.08-1.12), 1.19(1.17-1.21) and 1.27 (1.24-1.30), respectively. For each age group, the excess campylobacteriosis IRs in males differed at different age groups. However, despite some quantitative differences between countries, the excess was consistently present over long time-periods. In meta-regression analysis, age group was responsible for almost all the variation in the IRRs. CONCLUSIONS: The male predominance in campylobacteriosis IRs starts in infancy. This suggests that this is due, at least in part, to physiological or genetic differences and not just behavioural factors. These findings can provide clues to the mechanisms of the infection and could lead to more targeted treatments and vaccine development.

Sex differences in shigellosis incidence rates: analysis of national data from nine countries using meta-analytic method.

BACKGROUND: Sex differences in the incidence of infectious diseases can provide insight to the biological mechanism of infection, disease susceptibility, severity and vaccine development. The consistency of age-specific sex differences in the incidence rates (IRs) of shigellosis is unclear. METHODS: National data on cases of shigellosis by sex, age group and calendar year were obtained from nine countries, for a period of 6-25 years. The male to female incidence rate ratios (RR) were calculated by country, years and age group. For each age group, meta-analytic methods were used for computing pooled incidence RRs by country and years. Meta-regression was performed to estimate the contribution of age, country and time period to the differences in the male : female RRs. RESULTS: In the age groups <1, 1-4, 5-9 and 10-14, there were excess IRs in males. The pooled incidence RRs (with 95% CI) were 1.21 (1.14-1.28), 1.17 (1.12-1.22), 1.04 (1.00-1.09) and 1.09 (1.01-1.18), respectively. In young adults, there was excess IR in females with RR = 0.80 (0.72-0.9). In middle aged and older adults, there was a slight excess in males with RR = 1.01 (0.89-1.15) and RR = 1.18 (1.09-1.28), respectively. In the meta-regression, age was the only variable that significantly contributed to the variation in the RRs. CONCLUSIONS: The higher IRs in male infants and young children does not appear to be related to behavioral factors and genetic and hormonal factors could be important. In the older age groups, the higher rates in adult females may be due to behavioral factors.