Influenza Vaccination In Patients Research Articles

Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Patients with Moderate to Severe Asthma: The Phase3b VECTOR Study.

Annual influenza vaccinations are recommended for adolescents and adults with moderate to severe asthma. This study investigated the effect of tezepelumab, a human monoclonal antibody that blocks theactivity of thymic stromal lymphopoietin, on the humoral immune response to the quadrivalent seasonal influenza vaccine in patients with moderate to severe asthma. VECTOR was a phase3b, randomized, multicenter, double-blind, parallel-group, placebo-controlled study. Adolescents (aged12-17years) and young adults (aged18-21years) with moderate to severe asthma were enrolled across 15 centers in the USA. Patients received tezepelumab 210mg or placebo subcutaneously at weeks0, 4, 8, and 12, and a single dose of inactivated quadrivalent seasonal influenza vaccine at week12 before receiving study treatment. Immediately before vaccination and at 4weeks postvaccination (week16), strain-specific antibody responses were assessed for four influenza antigens by hemagglutination inhibition (HAI) and microneutralization (MN) assays. Safety was assessed. Seventy patients were randomized to tezepelumab (n = 35) or placebo (n = 35). There were no meaningful differences in HAI or MN antibody responses between treatment groups at week16. HAI assay geometric mean fold rises (GMFRs) for influenza strains were 1.76-7.34 for tezepelumab and 1.46-4.75 for placebo. MN assay GMFRs were 4.00-14.56 for tezepelumab and 3.56-10.62 for placebo. In the HAI assay, a fourfold or larger rise in antibody titer from weeks 12 to 16 occurred in 15.2-78.8% and 15.2-51.5% of tezepelumab and placebo recipients, respectively, and 97.0-100% of patients in both treatment groups achieved an antibody titer of at least40 at week16. No unexpected safety findings occurred. There was no observed suppression of the humoral immune response after influenza vaccination in adolescents and young adults with moderate to severe asthma treated with tezepelumab. Therefore, the influenza vaccine can be administered to this patient population during tezepelumab treatment. NCT05062759.

Antibody Responses to Influenza Vaccination are Diminished in Patients With Inflammatory Bowel Disease on Infliximab or Tofacitinib.

We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel disease [IBD]. We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling. Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20-0.60], p = 0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p = 0.0050), and tofacitinib (0.28 [0.14-0.57], p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p = 0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p = 0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p = 0.017), and tofacitinib (0.23 [0.10-0.56], p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 [r = 0.27; p = 0.0004] and H1N1 [r = 0.33; p < 0.0001]. Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses.

Influenza Vaccine Administration and Effectiveness Among Children and Adults With Glomerular Disease

IntroductionInfluenza infections contribute to excess healthcare utilization, morbidity, and mortality in individuals with glomerular disease, however influenza vaccination may not yield protective immune responses in this high-risk patient population. The objective of the present study was to describe influenza vaccine administration from 2010 to 2019 and explore the effectiveness of influenza vaccination in patients with glomerular disease. MethodsWe conducted an observational cohort study using healthcare claims for seasonal influenza vaccination (exposure) and influenza and influenza-like illness (outcomes) from commercially insured children and adults <65 years of age with primary glomerular disease in the Merative MarketScan® Research Databases. Propensity score-weighted cox proportional hazards models and ratio-of-hazard ratios (RHR) analyses were used to compare influenza infection risk in years where seasonal influenza vaccines matched or mismatched circulating viral strains. ResultsThe mean proportion of individuals vaccinated per season was 23% (range 19-24%). In pooled analyses comparing matched vs. mismatched seasons, vaccination was minimally protective for both influenza (RHR 0.86, 95% CI 0.52-1.41) and influenza-like illness (RHR 0.86, 95% CI 0.59-1.24), though estimates were limited by sample size. ConclusionsRates of influenza vaccination are suboptimal among patients with glomerular disease. Protection from influenza after vaccination may be poor, leading to excess infection-related morbidity in this vulnerable population.

Using peripheral immune-inflammatory blood markers in tumors treated with immune checkpoint inhibitors: An INVIDIa-2 study sub-analysis

The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of <3.4 (p<0.001) and <831 (p<0.001) were independent factors for OS in multivariate analysis. SII with LR, ROC, or CV significantly predicted OS in NSCLC (p= 0.002, p= 0.003, p= 0.003), RCC (p= 0.034, p= 0.014, p= 0.014), and melanoma (p= 0.038, p= 0.022, p= 0.019). NLR with LR and ROC cutoffs predicted OS in first line (p<0.001 for both) and second line or beyond (p= 0.006 for both); likewise SII (p<0.001; p= 0.002 and p<0.001). NLR and SII are prognosticators in NSCLC, RCC, and melanoma treated with ICIs.

Immunogenicity and safety of influenza vaccine in patients with lung cancer receiving immune checkpoint inhibitors: A single-center prospective cohort study

IntroductionPatients with lung cancer have a high risk of influenza complications. International guidelines recommend annual influenza vaccination for patients with cancer. Immune checkpoint inhibitors (ICIs) are progressively used to treat lung cancer. Data regarding immunogenicity and safety of influenza vaccine are limited in patients with lung cancer receiving ICIs; therefore, we conducted this single-center, prospective observational study in the Japanese population. MethodsPatients with lung cancer receiving ICIs and influenza immunization were enrolled. Blood samples were collected from patients for serum antibody titer measurement pre- and 4 ± 1 weeks post-vaccination. The primary endpoint was seroprotection rate (sP) at 4 ± 1 weeks post-vaccination. The secondary endpoints were geometric mean titer (GMT), mean fold rise, seroresponse rate (sR), seroconversion rate (sC), and immune-related adverse events (irAEs), defined as adverse effects caused by ICI administration, 6 months post-vaccination. ResultsInfluenza vaccination in the 23 patients included in the immunogenicity analyses significantly increased GMT for all strains, and sP, sR, and sC were 52%–91%, 26%–39%, and 26%–35%, respectively. In the 24 patients included in the safety analyses, 7 (29%) and 5 (21%) patients exhibited systemic and local reactions, respectively. Only one patient (4%) (hypothyroidism, grade 2) showed post-vaccination irAEs. ConclusionsOverall, influenza vaccination in patients with lung cancer receiving ICIs showed acceptable immunogenicity and safety, thus supporting annual influenza vaccination in this population.

Cluster randomized trial of influenza vaccination in patients with acute heart failure in China: A mixed-methods feasibility study.

Uncertainties about the efficacy of influenza vaccination for populations with heart failure (HF) in preventing cardiovascular outcomes, as well as lack of effective vaccination strategies, may contribute to low vaccine coverage rate (VCR) in China and globally. We assessed the feasibility of a strategy to promote influenza vaccines in patients hospitalized with acute HF in China and to inform the design of a hybrid effectiveness-implementation cluster randomized trial to evaluate this strategy on mortality and hospital re-admission. We conducted a cluster randomized pilot trial involving 11 hospitals in Henan Province in China, with mixed-methods evaluation between December 2020 and April 2021. A process evaluation involved interviews with 51 key informants (patients, health professionals, policy makers). The intervention included education about influenza vaccination and availability of free vaccines administered prior to hospital discharge for HF patients, while usual care included attending community-based points of vaccination (PoV) for screening and vaccination. Implementation outcomes focused on reach, fidelity, adoption, and acceptability. Recruitment rates were assessed for trial feasibility. Effectiveness outcomes were influenza VCR, HF-specific rehospitalizations and mortality at 90 days. A total of 518 HF patients were recruited from 7 intervention and 4 usual care hospitals (mean of 45 participants per hospital per month). VCR was 89.9% (311/346, 86.1-92.8%) in the intervention group and 0.6% (1/172, 0.0-3.7%) in the control group. The process evaluation demonstrated reach to patients with lower socioeconomic and education status. There was good fidelity of the intervention components, with education and PoV set up processes being adapted to local hospital workflow and workforce capacity. Intervention was acceptable and adopted by patients and health professionals. However, outside of a trial setting, concerns were raised around vaccination reimbursement costs, workforce accountability and capacity. The intervention strategy appears feasible and acceptable for improving VCR in HF patients at county-level hospitals in China. Trial registration: This pilot trial is registered with the acronym PANDA II Pilot (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2000039081).

Immune Response to Seasonal Influenza Vaccination in Multiple Sclerosis Patients Receiving Cladribine.

Cladribine has been approved for the treatment of multiple sclerosis (MS) and its administration results in a long-lasting depletion of lymphocytes. As lymphopenia is known to hamper immune responses to vaccination, we evaluated the immunogenicity of the influenza vaccine in patients undergoing cladribine treatment at different stages vs. controls. The antibody response in 90 cladribine-treated MS patients was prospectively compared with 10 control subjects receiving platform immunotherapy (NCT05019248). Serum samples were collected before and six months after vaccination. Response to vaccination was determined by the hemagglutination-inhibition test. Postvaccination seroprotection rates against influenza A were comparable in cladribine-treated patients and controls (H1N1: 94.4% vs. 100%; H3N2: 92.2% vs. 90.0%). Influenza B response was lower in the cladribine cohort (61.1% vs. 80%). The increase in geometric mean titers was lower in the cladribine group vs. controls (H1N1: +98.5 vs. +188.1; H3N2: +225.3 vs. +300.0; influenza B: +40.0 vs. +78.4); however, titers increased in both groups for all strains. Seroprotection was achieved irrespective of vaccination timing and lymphocyte subset counts at the time of vaccination in the cladribine cohort. To conclude, cladribine-treated MS patients can mount an adequate immune response to influenza independently of treatment duration and time interval to the last cladribine administration.

Influenza Vaccination among Patients with Diabetes or Ischemic Heart Disease in Thailand: Coverage, Knowledge and Associated Factors.

An influenza vaccination is recommended for patients with diabetes mellitus (DM) or ischemic heart disease (IHD) to prevent cardiovascular events, but the vaccination coverage remains low. This cross-sectional study sought to investigate vaccination coverage, knowledge level on influenza and factors associated with influenza vaccination in patients with DM or IHD treated at a tertiary hospital in northern Thailand. Patients were interviewed from August to October 2017. Of 150 patients interviewed (51.3% women, mean age of 66.7 ± 8.3 years, 35.3% DM, 35.3% IHD, 29.3% DM and IHD), 45.3% (68/150) were vaccinated against influenza. The mean knowledge score was 9.68 ± 1.35 (total: 11) and did not differ between those receiving the immunization and those who did not (p = 0.056). Two factors remained significantly associated with their vaccination after multivariable logistic regression analysis: knowing their right to receive free vaccinations (adjusted OR 2.32, 95% CI: 1.06-5.10, p-value: 0.035), and needing to be vaccinated (adjusted OR 3.50, 95% CI: 1.51-8.12, p-value: 0.003). Overall, the vaccine coverage was low; less than one-half of patients received the influenza vaccine, but their knowledge level was high. Possessing the right and having a need were two factors associated with vaccination. Such factors should be carefully considered to encourage patients with DM and IDH to receive the influenza vaccination.

Vaksinasi Influenza sebagai Prediktor Terjadinya Kejadian Rawat Inap Akibat Kejadian Kardiovaskular pada Pasien dengan Riwayat Penyakit Jantung Koroner: Suatu Laporan Kasus Berbasis Bukti

Influenza is known to worsen cardiovascular events in patients with a history of coronary heart disease. However, the effectiveness of influenza vaccination in reducing hospitalization due to cardiovascular disease is not clearly known. We aim to determine the effect of influenza vaccination on hospitalization rates due to cardiovascular disease in patients with a history of coronary heart disease. Relevant literature was searched on four electronic databases: MEDLINE, EMBASE, SCOPUS, and Cochrane Library, using predetermined keywords. Critical review of the studies was done using the Center of Evidence Based Medicine (CEBM) University of Oxford assessment tool. The search yielded six articles, and critical review was done based on validity, importance, and applicability. Three studies showed that influenza vaccination in patients with coronary heart disease would reduce hospitalization rates due to cardiovascular disease within 12 months after vaccination. Three studies did not show any effect of influenza vaccination on hospitalization rates due to cardiovascular disease. The samples in the three studies that found a protective effect of the influenza vaccine were older and at higher risk of experiencing cardiovascular events. Based on our review, we conclude that influenza vaccination can be given to prevent hospitalization due to cardiovascular disease in patients with a history of coronary heart disease, especially in high-risk patients.

Knowledge, attitudes and practices of health care workers in a cardiology department on influenza vaccination.

Evidence has accrued that influenza vaccination may be effective in preventing myocardial infarction (MI). However, vaccination rates in both adults and health care workers (HCW) are low, and hospitalisation is often a missed opportunity for vaccination. We hypothesised that knowledge, attitude and practices of health care workers regarding vaccination impacts vaccine uptake in hospitals. The cardiac ward admits high-risk patients, many of whom are indicated for influenza vaccine, especially those caring for patients with acute MI. To understand the knowledge, attitudes, and practices of HCW in cardiology ward within a tertiary institution, on influenza vaccination. We used focus group discussions with HCW caring for AMI patients in an acute cardiology ward, to explore the knowledge, attitudes, and practices of HCW regarding influenza vaccination for patients under their care. Discussions were recorded, transcribed, and thematically analysed using NVivo software. In addition, participants completed a survey on their knowledge and attitudes towards the uptake of influenza vaccination. A lack of awareness regarding the associations between influenza, vaccination and cardiovascular health was identified amongst HCW. Participants did not routinely discuss the benefits of influenza vaccination or recommend influenza vaccinations to patients under their care; this may be due to a combination of a lack of awareness, not seeing it as part of their job and workload issues. We also highlighted difficulties in access to vaccination, and concerns of adverse reactions to the vaccine. There is limited awareness among HCW of the role of influenza on cardiovascular health and the benefits of influenza vaccine in the prevention of cardiovascular events. Improved vaccination of at-risk patients in hospital may need active engagement of HCW. Improving the health literacy of HCW regarding the benefits of vaccination as a preventative strategy may result in better health care outcomes for cardiac patients.

Influenza Vaccination as Prevention Therapy for Stable Coronary Artery Disease and Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials

BackgroundInfluenza can cause a significant burden on patients with coronary artery disease. This meta-analysis assessed the effectiveness of influenza vaccination in patients with acute coronary syndrome and stable coronary artery disease. MethodsWe searched the Cochrane Controlled Register of Trials (CENTRAL), Embase, MEDLINE, www.ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to September 2021. Estimates were summarized using the Mantel-Haenzel method and a random-effects model. To assess heterogeneity the I² statistic was used. ResultsFive randomized trials, comprising 4187 patients, were included, 2 of which included patients with acute coronary syndrome and 3 that included patients with stable coronary artery disease and acute coronary syndrome. Influenza vaccination significantly reduced the risk for all-cause mortality (relative risk [RR] = 0.56; 95% confidence interval [CI], 0.38-0.84), cardiovascular mortality (RR = 0.54; 95% CI, 0.37-0.80), major acute cardiovascular events (RR = 0.66; 95% CI, 0.49-0.88), and acute coronary syndrome (RR = 0.63; 95% CI, 0.44-0.89). On subgroup analysis, influenza vaccination remained effective for these outcomes in acute coronary syndrome but did not meet statistical significance in coronary artery disease. Furthermore, influenza vaccination did not reduce the risk for revascularization (RR = 0.89; 95% CI, 0.54-1.45), stroke or transient ischemic attack (RR = 0.85; 95% CI, 0.31-2.32), or heart failure hospitalization (RR = 0.91; 95% CI, 0.21-4.00). ConclusionsInfluenza vaccine is a cheap and effective intervention to reduce the risk for all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome among coronary artery disease patients, especially in those with acute coronary syndrome.

Influenza vaccination in patients affected by diabetes.

Type 2 diabetes, obesity-related metabolic syndrome, and insulin resistance are the most common metabolic disorders associated with increased cardiovascular risk. In addition, patients with Type 2 diabetes have an increased risk for a more severe course of influenza virus infection, a common pandemic. There is increasing evidence that influenza vaccination in patients with diabetes can safely and effectively reduce all-cause mortality and cardiovascular death. The effects of vaccination appear to be more effective when using higher-dose and quadrivalent vaccines, although subgroup-specific separate analyses in patients with diabetes are lacking. Clinical recommendations address influenza vaccination in all adults with diabetes. From our point of view, it should be an integral part of treatment strategies in patients with diabetes.

Healthcare Providers' Adherence to Recommended Pneumococcal and Influenza Vaccination in Patients Discharged with Respiratory Diseases from General Medical Wards.

The periodic assessment of adherence to vaccination recommendations is an essential component of any vaccination process. This study aimed to investigate the adherence of healthcare providers to the international recommendations on influenza and pneumococcal vaccine in patients discharged from the internal medicine department with respiratory diseases. All medical records of adult patients who are 18 years of age and older with respiratory illnesses and who were discharged in January-February, May-June, and October-November of 2018 were retrospectively analyzed. A total of 264 discharge summaries from 190 patients were included in this analysis. The mean age was 55.5 years, with 54.7% of them being males. Pneumonia was the leading cause of hospitalization (63.7%), followed by asthma or chronic obstructive pulmonary disease (COPD) exacerbation (27.4%). None of the discharged patients had immunization recommendations at discharge or a documented immunization request within 6 months of discharge from the hospital. The findings of this study demonstrated that healthcare providers need to pay more attention to adhering to the global recommendations on influenza and pneumococcal vaccine among patient who were recently discharged with respiratory disease. Additional measures are needed to improve adherence to routinely recommended vaccines among adults with respiratory diseases.

Influenza vaccination trend and related factors among patients with diabetes in Korea: Analysis using a nationwide database.

Subjects with diabetes are at higher risk of serious influenza-related complications. We aimed to investigate the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza in subjects with diabetes using a nationwide observational study performed within the recent decade. Among 105,732 subjects from the Korea National Health and Nutrition Examination Survey between 2007 and 2019, 8,632 with diabetes were included. We investigated the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza. During the study period, the prevalence of influenza vaccination in subjects with diabetes showed a tendency to increase every year, reaching almost 60% in 2019, which was higher than the rate in subjects without diabetes. Younger age (adjusted hazard ratio (aHR) [95% CI] 11.29 [8.63-14.75] for < 50 years; 6.16 [5.21-7.29] for 50-65 years), male (aHR 1.67 [1.52-1.87]), current smoker (aHR 1.31 [1.00-1.72], lower-income status (aHR 1.46 [1.17, 1.84]), and high education level (aHR 1.30 [1.01-1.67]) were associated with being unvaccinated. Also, a poorer glycemic control with HbA1c ≥ 9% was found to be correlated with unvaccinated status (aHR 1.48 [1.15-1.90]). The influenza vaccination rate is still unsatisfactory in subjects with diabetes. Young age, males, low-income level, high education level, and poor glycemic control were associated with unvaccinated status. Considering the risk-benefits of influenza vaccination in patients with diabetes, physicians should make an effort to increase vaccination rates, especially in low vaccination rate groups.

Effect of Influenza Vaccination in Patients with Cardiovascular Disease: An Updated Meta-Analysis of Randomized Controlled Trials

Background: Influenza is a major cause of morbidity and mortality in patients with cardiovascular disease (CVD). The aim of this updated systematic review and meta-analysis was to evaluate the effect of influenza vaccination (IV) on morbidity and morbidity in adult patients with CVD. Methods: We conducted a systematic review and meta-analysis (PubMed, Cochrane Library, International Clinical Trials Registry Platform, and manual search of conference presentations) of randomized clinical trials published up to April 2022 analyzing whether IV reduced all-cause mortality in adult patients with CVD, including heart failure (HF) and coronary artery disease (CAD), compared with patients who were not vaccinated. Results: A total of six clinical trials comprising 9316 patients were analyzed. Five trials included CAD patients, and one trial included HF patients. Mean follow-up was 16 ± 9.7 months. Influenza vaccine was associated with a reduction of mortality compared to controls: relative risk (RR) 0.67, 95% confidence interval (95% CI), 0.47-0.95; p = 0.03; I2 = 53%, and with reduction of cardiovascular death compared to controls: RR 0.64; 95% CI 0.44-0.94; p = 0.02; I2 = 54%. There was a non-statistically significant reduction in myocardial infarction compared to control: RR 0.82, 95% CI 0.60-1.12; p = 0.57; I2 = 0%. Conclusion: In this meta-analysis of six randomized controlled clinical trials, IV was associated with a 33% and 36% relative risk reduction of all-cause mortality and cardiovascular death, respectively, in patients with CVD. We sought to promote consensus about the persistent benefits of influenza vaccination in patients with CVD by including two new clinical trials in CAD and HF, confirming the association of vaccination with risk reduction in subjects with CVD.

Impact of Therapy on the Anamnestic Response to Seasonal Influenza Vaccination in Patients with Myeloid Malignancies

Myelodysplastic syndromes (MDS) are diseases of bone marrow failure that result in dysplasia of multiple hematopoietic lineages producing anemia, thrombocytopenia, and increased risk of infections. While progression to acute myeloid leukemia (AML) is a phenomenon that receives most of the focus in managing this disease, prior studies have shown that infection is the leading cause of mortality. This is true across all MDS risk groups and highlights the critical importance of research into the clinical management and prevention of infection in patients with MDS, especially in the age of emergent pandemics such as COVID-19. We have previously observed that patients with MDS exhibit decreased responses to vaccination against SARS-CoV-2 (Bellusci, et al., Blood, 2022). There remains a gap in our knowledge regarding the success of vaccination against common seasonal pathogens in patients with MDS, such as influenza. Although patients with MDS and AML are routinely offered yearly influenza vaccination during the flu season, the efficacy of vaccination in producing immunity in the context of the underlying disease biology and the impact of therapies used for treatment of the disease (azacitidine & decitabine (HMAs), venetoclax + HMA and cytarabine based intensive chemotherapy) remains understudied. We hypothesized that MDS/AML patients would exhibit a decreased response to vaccination against seasonal influenza compared to healthy age-matched controls. To test this hypothesis, we enrolled patients in an IRB-approved non-randomized study (I-54017) that spanned the 2017-2018 to 2020-2021 influenza seasons. This study examined 5 patient groups: Cohort 1: Patients with MDS on best supportive care (ESAs, growth factors, transfusions, antibiotics; no disease modifying therapy; n = 28); Cohort 2: Patients with MDS or AML early in HMA therapy (≤5 cycles; n = 26); Cohort 3: Patients with MDS or AML on longer term HMA (> 6 cycles; n = 28); Cohort 4: Patients with AML receiving cytarabine based intensive chemotherapy ("7+3", HIDAC, CLAG+/-M, FLAG+/-Ida, etc.). Patients in this arm should not have received an HMA in the 6 months prior to enrollment (n = 10); Cohort 5: Healthy volunteers of similar age profile without antecedent or concurrent hematologic disorders (n = 12). All subjects received the yearly Fluzone High-Dose vaccine (Sanofi). Serum samples were collected at 1) baseline; 2) days 25-95 after vaccination; and 3) days 115-185 after vaccination. Viral titers were measured using the viral microneutralization assay against seasonal influenza vaccine strains based upon the yearly vaccine product. Positive responses to vaccination were defined as a 4-fold increase in titer compared to baseline. For each subject, we calculated a strain score (range 0-1) based on the fraction of 4-fold changes across either 3 to 4 influenza strains depending upon the yearly vaccination product; a score of 1 indicates a 4-fold increase in titers against all tested strains. Strain score was modeled as a function of study year, disease cohort, and age; blood-type, gender, race, and IPSS-M were analyzed but were not statistically significant. The primary analysis was a generalized linear model (GLM). In concert with prior reports, we found that compared to healthy donors, AML patients receiving intensive chemotherapy showed decreased vaccine response (Fig.1). In contrast, those with MDS responded equivalently to vaccination compared with healthy donors. Overall, these results demonstrate that in contrast with vaccination against newly emergent diseases (COVID-19) against which MDS patients appear to have inferior immune response, anamnestic responses to vaccination against previously encountered pathogens (influenza) are normal. As reported previously, patients with AML receiving intensive chemotherapy exhibit reduced protection from vaccination against both emergent pathogens (COVID-19) and amnestic vaccines (influenza). These results indicate that vaccination boosters, such as those given yearly against influenza, against previously encountered pathogens are likely to provide protection in MDS patients irrespective of standard therapy, but the efficacy of vaccination against novel pathogens may be less effective. These data highlight the complex immune milieu in patients with MDS and emphasize the importance of careful individualized vaccination strategies in those with hematological malignancy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The link between influenza and myocardial infarction: vaccination protects

The association between influenza and cardiovascular disease has been known since the influenza pandemics of the early years of the last century. This association is more consistent and more lasting in the case of particularly severe infections. Several pathogens, including influenza viruses, can modulate the inflammatory response and influence the biology of atherosclerotic plaque to rupture it and cause a Type 1 myocardial infarction. Clinically relevant viral infections can also exacerbate pre-existing cardiovascular disease and contribute to the development of a Type 2 myocardial infarction through an increase in the metabolic demands of the myocardial tissue for fever and tachycardia and the possible induction of hypoxaemia. Evidence of a relevant protective efficacy of influenza vaccination provides further robust and convincing support for a causal link between influenza and myocardial infarction. Consistent cardiovascular protection linked to influenza vaccination has also been demonstrated in patients with recent myocardial infarction to suggest the possibility that this procedure may become an integral part of in-hospital management of acute coronary syndromes. Despite the solidity of these evidences, acknowledged by the guidelines that recommend influenza vaccination in patients at increased cardiovascular risk, still today an unacceptably high proportion of patients at high cardiovascular risk do not receive flu vaccination. Despite some potential limitations of the current flu vaccination, its advantages in terms of reducing cardiovascular events and related mortality are still such as to justify its wide use, especially, but not limited to, in patients with high cardiovascular risk.

Influenza vaccination and risk of atrial fibrillation in patients with gout: A nationwide population-based cohort study.

Objective: Although influenza vaccination reduces the risk of atrial fibrillation (AF), its protective effect in patients with gout remains unclear. The present study aimed to evaluate the protective effect of influenza vaccination in patients with gout. Methods: A total of 26,243 patients with gout, aged 55 and older, were enrolled from the National Health Insurance Research Database (NHIRD) between 1 January 2001, and 31 December 2012. The patients were divided into vaccinated (n = 13,201) and unvaccinated groups (n = 13,042). After adjusting comorbidities, medications, sociodemographic characteristics, the risk of AF during follow-up period was analyzed. Results: In influenza, non-influenza seasons and all seasons, the risk of AF was significantly lower in vaccinated than in unvaccinated patients (Adjust hazard ratio [aHR]: 0.59, 95% confidence interval [CI]: 0.50–0.68; aHR: 0.50, 95% CI: 0.42–0.63; aHR: 0.55, 95% CI: 0.49–0.62, respectively). In addition, the risk of AF significantly decreased with increased influenza vaccination (aHR: 0.85, 95% CI: 0.69–1.04; aHR: 0.72, 95% CI: 0.60–0.87; aHR: 0.40, 95% CI: 0.33–0.49, after first, 2–3 times, and ≥4 times of vaccination, respectively). Furthermore, sensitivity analysis indicated that the risk of AF significantly decreased after influenza vaccination for patients with different sexes, medication histories, and comorbidities. Conclusions: Influenza vaccination is associated with a lower risk of AF in patients with gout. This potentially protective effect seems to depend on the dose administered.

Preliminary evidence that daily light exposure enhances the antibody response to influenza vaccination in patients with dementia

Enhancing lighting conditions in institutions for individuals with dementia improves their sleep, circadian rhythms and well-being. Here, we report first findings that exposure to brighter light during daytime may support the immune response to the annual influenza vaccination. Eighty older institutionalised patients suffering from dementia (54 women and 26 men) continuously wore an activity tracker for 8 weeks to assess individual light exposure and rest-activity cycles. We analysed the patients’ immune response from two blood samples taken before and 4 weeks after the annual influenza vaccination. Individual antibody concentrations to three influenza virus strains (H3N2, H1N1, IB) were quantified via hemagglutination inhibition assays. By quantifying individual light exposure profiles (including daylight), we classified the patients into a low and a high light exposure group based on a median illuminance of 392.6 lux. The two light exposure groups did not differ in cognitive impairment severity, age or gender distribution. However, patients in the high light exposure group showed a significantly greater circadian rest-activity amplitude (i.e., more daytime activity and less nighttime activity) along with a significantly greater antibody titer increase to the H3N2 vaccine than patients in the low light exposure group, despite similar pre-vaccination concentrations. Sufficient seroprotective responses to all three influenza virus strains were attained for ≥75% of participants. These data provide preliminary evidence for a potentially enhanced immune response in patients with dementia when they received more daily light. Future studies are needed to determine whether regular daily light exposure may have beneficial effects on the human immune system, either directly or via a stabilising circadian sleep-wake rhythms.

Association between Stroke Risk and Influenza Vaccination in Patients with Gout: A Nationwide Population-Based Study.

The risk of stroke in patients with gout is high. The effect of vaccines in lowering the stroke risk in patients with gout remains unclear. We retrospectively analyzed 23,949 patients with gout (age ≥ 55 years) from the National Health Insurance Research Database over a 12-year period. The patients were divided into vaccinated (n = 11,649) and unvaccinated groups (n = 12,300). Overall, the vaccinated group had significantly lower risks of all stroke, hemorrhagic stroke, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR], 0.59 and 95% confidence interval [CI], 0.55–0.63; aHR, 0.60 and 95% CI, 0.49–0.73; and aHR, 0.60 and 95% CI, 0.55–0.65, respectively). The association appeared to be dose-dependent for both hemorrhagic and ischemic stroke (hemorrhagic stroke: aHR, 0.81 and 95% CI, 0.61–1.08; aHR, 0.80 and 95% CI, 0.62–1.02; and aHR, 0.37 and 95% CI, 0.28–0.48; ischemic stroke: aHR, 0.83 and 95% CI, 0.74–0.94; aHR, 0.73 and 95% CI, 0.65–0.81; and aHR, 0.42 and 95% CI, 0.38–0.47 for patients vaccinated 1, 2 or 3, and ≥4 times, respectively, during the follow-up period). Patients with a history of atrial fibrillation did not have a lower risk of hemorrhagic stroke even after receiving four vaccinations (aHR, 0.59; 95% CI, 0.25–1.38). Influenza vaccination was associated with a lower risk of all stroke in people with gout, and the association appeared to be dose-dependent.