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.

Background: Massive DNA destruction/accumulation of cell-free DNA debris is a sensitive biomarker of progressive organ/tissue damage. Deleterious consequences of DNA debris accumulation are evident in cardiac ischemia, thrombosis, auto-inflammatory diseases, SLE-induced lupus nephritis and cystic fibrosis. In case of renal pathologies, degradation and elimination of DNA debris are suppressed, due to downregulated DNAse-I activity within the diseased kidneys. The aim of the current study was to evaluate whether exogenous DNAse-I administration might exert renoprotective effects in the setting of acute kidney injury (AKI or acute renal failure). Methods: Sprague-Dawley rats underwent unilateral nephrectomy, with simultaneous clamping of contralateral kidney artery. The treated group received DNAse-I injection before discontinuing anesthesia. Positive (ischemic) controls received saline injection. Negative (non-ischemic) controls were either non-operated or subjected to surgery of similar duress and duration without ischemia. Renal perfusion was evaluated using the Laser-Doppler technique. Blood was procured for evaluating DNAse-I activity, renal functioning, renal perfusion. The kidneys were allocated for histopathologic examinations and for the evaluation of renal hypoxia, intra-renal apoptosis and proliferation. Results: Contrary to the situation in untreated ischemic rats, renal perfusion was significantly improved in DNAse-treated animals, concomitantly with significant amelioration of damage to renal functioning and tissue integrity. Treatment with DNAse-I significantly decreased the ischemia-induced renal hypoxia and apoptosis, simultaneously stimulating renal cell proliferation. Exogenous DNAse-I administration accelerated the clearance of intra-renal apoptotic DNA debris. Conclusion: Functional/histologic hallmarks of renal injury were ameliorated, renal functioning improved, intra-renal hypoxia decreased and intra-renal regeneration processes were activated. Thus, DNAse-I treatment protected the kidney from deleterious consequences of ischemia-induced AKI.

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.

Background: Sex can be an important biological variable in the immune response to infections and the response to vaccines. The magnitude and consistency in age-specific sex differences in the incidence of viral infections remain unclear. Methods: We obtained data from national official agencies on cases of viral meningitis by sex and age group over a period of 6-16 years from five countries: Canada, Czech Republic, Germany, Israel, and Poland. Male to female incidence rate ratios (RR) were computed for each year, by country, and age group. For each age group, we used meta-analysis methodology to combine the incidence RRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the RR. Findings: In the age groups < 1, 1-4, 5-9, 10-14, there were consistently higher incidence rates in males, over countries and time. The pooled incidence RRs (with 95% CI) were 1.38 (1.30-1.47), 1.94 (1.85-2.03), 1.98 (1.88-2.07), and 1.58 (1.47-1.71) respectively. In young and middle-age adults there were no differences with pooled incidence RRs of 1.00 (0.97-1.03), and 0.97 (0.94-1.00), respectively. Sensitivity analysis confirms that the results are stable and robust. Meta-regression showed that almost all the variations in the incidence RRs were contributed by age group. Interpretation: The higher incidence rates from viral meningitis in males under the age of 15 are remarkably consistent across countries and time-periods. These findings emphasize the importance of sex as a biological variable in infectious diseases. This could provide keys to the mechanisms of infection and lead to more personalized treatment and vaccine doses and schedules. Funding: There was no funding source for this article.

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.

No abstract

Background Pertussis is frequently reported to be more common in females than in males. However, the variability of the sources of these observations makes it difficult to estimate the magnitude and consistency of the sex differences by age. To address this question, we used meta-analytic methods to analyze pertussis national incidence rates by sex and age group from nine countries between the years 1990 and 2017. Methods For each age group, we used meta-analytic methods to combine the female to male incidence rate ratios (RRs) by country and year. Meta-regression was performed to assess the relative contributions of age, country and time-period to the variation in the incidence RRs. Results The pooled female to male incidence RRs (with 95% CI) for ages 0

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 &lt;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.