Vaccine effectiveness against COVID-19 among symptomatic persons aged ≥12 years with reported contact with COVID-19 cases, February-September 2021

BACKGROUND: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood. METHODS: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression. RESULTS: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2). CONCLUSIONS: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage

Are children's vitamin D levels and BMI associated with antibody titers produced in response to 2014–2015 influenza vaccine?

Background: Vitamin D is an immunomodulating hormone, which has been associated with susceptibility to infectious diseases. Methods: Serum vitamin D levels in 135 children ages 3–17 y were measured at baseline and hemagglutinin influenza antibody titers were measured pre- and 21 d post influenza vaccination with live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV). Height and weight were derived from the electronic medical record and were used to calculate body mass index (BMI). Results: Thirty-nine percent of children were ages 3–8 years; 75% were black, 34% were obese (BMI ≥ 95th percentile); vitamin D levels were >20 ng/ml in 55%. In linear regression analyses, post vaccination antibody titers for LAIV B lineages (B Brisbane and B Massachusetts) were significantly higher among those with lower vitamin D levels and among younger participants (P < 0.05). No associations between vitamin D levels and responses to LAIV A strains (A/H1N1 and A/H3N2) or to any IIV strains or lineages were found. Conclusion: Low vitamin D levels were associated with higher response to LAIV B lineages in the 2014–2015 LAIV, but not related to LAIV A or any IIV strains

Effect of mild COVID-19 on health-related quality of life

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life. Methods: This prospective observational study of symptomatic adults (18–87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6–8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up. Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P < 0.001) and non-COVID cases (3.3 ± 0.32; P < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P < 0.001) and decreased significantly for non-COVID cases (−0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (β = 1.17; SE = 0.5; P = 0.021), having COVID-19 (β = 1.99; SE = 0.54; P < 0.001); and non-white race (β = −2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (β = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (β = 2.42; SE = 0.67; P < 0.001). Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6–8 weeks’ convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females

The effect of frailty on HAI response to influenza vaccine among community-dwelling adults ≥ 50 years of age

The immune response to vaccine antigens is less robust in older adults because of changes in the aging immune system. Frailty, the multi-dimensional syndrome marked by losses in function and physiological reserve, is increasingly prevalent with advancing age. Frailty accelerates this immunosenescence but the consequence of frailty on immune response specific to influenza vaccine among older adults, is mixed. An observational, prospective study of 114 adults was conducted in the fall of 2013 to assess the association of physical frailty with immune response to standard dose influenza vaccine in community-dwelling adults ≥ 50 years of age. Participants were stratified by age (<65 years and ≥65 years), and vaccine strain (Influenza A/H1N1, A/H3N2 and B) was analyzed separately adjusting for body mass index (BMI) and baseline log2 hemagglutination inhibition (HAI) titers. Overall, immune responses were lower among those ≥65 years of age than those <65 years. Among those ≥65 years there were no significant differences between frail and non-frail individuals in seroprotection or seroconversion for any influenza strain. Frail individuals <65 years of age compared with non-frail individuals were more likely to be seroprotected and to seroconvert post vaccination. Linear regression models show the same pattern of significant differences between frail and non-frail for those <65 years but no significant differences between frailty groups for those ≥65 years. Additional research may elucidate the reasons for the differences observed between younger frail and non-frail adults

Using the 4 pillars™ practice transformation program to increase adult influenza vaccination and reduce missed opportunities in a randomized cluster trial

Abstract Background An evidence-based, step-by-step guide, the 4 Pillars™ Practice Transformation Program, was the foundation of an intervention to increase adult immunizations in primary care and was tested in a randomized controlled cluster trial. The purpose of this study is to report changes in influenza immunization rates and on factors related to receipt of influenza vaccine. Methods Twenty five primary care practices were recruited in 2013, stratified by city (Houston, Pittsburgh), location (rural, urban, suburban) and type (family medicine, internal medicine), and randomized to the intervention (n = 13) or control (n = 12) in Year 1 (2013-14). A follow-up intervention occurred in Year 2 (2014-15). Demographic and vaccination data were derived from de-identified electronic medical record extractions. Results A cohort of 70,549 adults seen in their respective practices (n = 24 with 1 drop out) at least once each year was followed. Baseline mean age was 55.1 years, 35 % were men, 21 % were non-white and 35 % were Hispanic. After one year, both intervention and control arms significantly (P < 0.001) increased influenza vaccination, with average increases of 2.7 to 6.5 percentage points. In regression analyses, likelihood of influenza vaccination was significantly higher in sites with lower percentages of patients with missed opportunities (P < 0.001) and, after adjusting for missed opportunities, the intervention further improved vaccination rates in Houston (lower baseline rates) but not Pittsburgh (higher baseline rates). In the follow-up intervention, the likelihood of vaccination increased for both intervention sites and those that reduced missed opportunities (P < 0.005). Conclusions Reducing missed opportunities across the practice increases likelihood of influenza vaccination of adults. The 4 Pillars™ Practice Transformation Program provides strategies for reducing missed opportunities to vaccinate adults. Trial registration This study was registered as a clinical trial on 03/20/2013 at ClinicalTrials.gov, Clinical Trial Registry Number: NCT01868334 , with a date of enrollment of the first participant to the trial of April 1, 2013

Differential gene expression in peripheral blood mononuclear cells from children immunized with inactivated influenza vaccine

The human immune response to inactivated influenza vaccine is dynamic and impacted by age and preexisting immunity. Our goal was to identify postvaccination transcriptomic changes in peripheral blood mononuclear cells from children. Blood samples were obtained before and at 3 or 7 days postvaccination with 2016–2017 quadrivalent inactivated influenza vaccine and RNA sequencing was performed. There were 1,466 differentially expressed genes (DEGs) for the Day 0–Day 3 group and 513 DEGs for the Day 0–Day 7 group. Thirty-three genes were common between the two groups. The majority of the transcriptomic changes at Day 3 represented innate inflammation and apoptosis pathways. Day 7 DEGs were characterized by activation of cellular processes, including the regulation of cytoskeleton, junctions, and metabolism, and increased expression of immunoglobulin genes. DEGs at Day 3 were compared between older and younger children revealing increased inflammatory gene expression in the older group. Vaccine history in the year prior to the study was characterized by robust DEGs at Day 3 with decreased phagosome and dendritic cell maturation in those who had been vaccinated in the previous year. PBMC responses to inactivated influenza vaccination in children differed significantly by the timing of sampling, patient age, and vaccine history. These data provide insight into the expected molecular pathways to be temporally altered by influenza vaccination in children

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains.

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or 'back-boosting' to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre-existing immunity in people of different ages is critical for designing the next-generation of 'universal' or broadly-protective influenza vaccines