Objective: Despite the progression of treatments over decades, heart failure (HF) is a disease with high morbidity, mortality and economic burden. Influenza infection is an important trigger for cardiovascular (CV) events, including HF. Influenza vaccination has been seen to reduce the risk of CV mortality in patients with coronary disease, but the effect in patients with HF is still unclear. Therefore, we conducted a systematic review to evaluate the effect of influenza vaccination in the morbimortality of patients with HF. Methods: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Technology Assessment and PsycINFO databases (December 2018) were searched for longitudinal studies evaluating influenza vaccination compared with a non-vaccination control group in patients with HF. The risk of bias was assessed according to the ROBINS-I tool. We performed a random-effects meta-analysis to estimate the pooled HRs with 95% CIs, and heterogeneity was evaluated using the I² statistics. Results: Six cohort studies evaluating 179 158 patients with HF were included in the meta-analysis. Influenza vaccination was associated with a lower risk of all-cause mortality (HR=0.83; 95% CI 0.76 to 0.91; I²=75%). The effect of the influenza vaccination was not statistically significant in a pooled analysis of CV mortality (HR=0.92, 95% CI 0.73 to 1.15; 2 studies) and of all-cause hospitalisations (HR=1.01, 95% CI 0.92 to 1.11; 2 studies). The majority of outcomes in the included studies had a serious risk of bias and almost all evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation (GRADE) evidence. Conclusions: Influenza vaccination was associated with a significant decrease in all-cause mortality risk in patients with HF.

Introduction: Influenza vaccination may be beneficial in coronary disease patients; however the infection and vaccination are associated to acute inflammation, a trigger of cardiovascular events. We aimed to review the risk of myocardial infarction (MI) associated with Influenza infection and the safety of vaccination in self-controlled case series (SCCS). Methods: We performed a systematic review with meta-analysis of SCCS studies to evaluate the risk of MI associated with Influenza infection or vaccination. Database search was performed in August 2018. The data were reported using the incident rate ratio (IRR) and 95% confidence interval (95%CI). Results: 3 studies for Influenza infection and 2 studies for Influenza vaccination were eligible. The risk of MI following an Influenza infection (3 studies) was significantly increased in the first 3 days (IRR 5.79; 95%CI: 3.59-9.38) and between 4-7 days (IRR 4.52; 95%CI: 2.80-7.32). In the first 4 weeks following the vaccination against Influenza there was a significant decrease of MI risk (IRR 0.84, 95%CI: 0.78-0.91). Conclusions: Short-term MI risk in Influenza infection is significantly increased, with a low-to-moderate confidence in the pooled evidence. The Influenza vaccine was safe regarding short-term risk for MI, and the significant risk reduction is possibly related to a healthy period bias.

Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. Methods: A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes’ VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. Results: The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [p = 0.002] and seventh [p < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes’ VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. Conclusion: Supplementation with higher doses of cholecalciferol may contribute to a significant increase in 25vitD levels but not in LL37 levels. Higher LL37 levels on admission may be related to a decrease in ICU, hospital, and 60-day mortality. VDR gene expression in monocytes is much higher in patients supplemented with higher doses of cholecalciferol.