Explore the vast range of titles available.

•Age and baseline HAI titers were associated with immune response to egg-free influenza vaccine.•HAI response differed by antigen level contained in prior season’s influenza vaccine.•The ideal sequence of vaccine formulations across influenza seasons remains unknown. Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.

Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children’s and young adults’ HAI titers against the 2019–2020 LAIV4 and ccIIV4. Participants aged 4–21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21–35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4–3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178–237); cell = 136 (95% CI:113–165); LAIV4 day 28: egg = 96 (95% CI: 83–112); cell = 63 (95% CI: 58–74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.

Influenza vaccines can mitigate illness severity, including reduced risk of ICU admission and death, in people with breakthrough infection. Less is known about vaccine attenuation of mild/moderate influenza illness. We compared subjective severity scores in vaccinated and unvaccinated persons with medically attended illness and laboratory-confirmed influenza. Participants were prospectively recruited when presenting for care at five US sites over nine seasons. Participants aged ≥ 16 years completed the EQ-5D-5L visual analog scale (VAS) at enrollment. After controlling for potential confounders in a multivariable model, including age and general health status, VAS scores were significantly higher among 2,830 vaccinated participants compared with 3,459 unvaccinated participants, indicating vaccinated participants felt better at the time of presentation for care. No differences in VAS scores were observed by the type of vaccine received among persons aged ≥ 65 years. Our findings suggest vaccine-associated attenuation of milder influenza illness is possible.

ABSTRACT Background The 2022–23 US influenza season peaked early in fall 2022. Methods Late‐season influenza vaccine effectiveness (VE) against outpatient, laboratory‐confirmed influenza was calculated among participants of the US Influenza VE Network using a test‐negative design. Results Of 2561 participants enrolled from December 12, 2022 to April 30, 2023, 91 laboratory‐confirmed influenza cases primarily had A(H1N1)pdm09 (6B.1A.5a.2a.1) or A(H3N2) (3C.2a1b.2a.2b). Overall, VE was 30% (95% confidence interval −9%, 54%); low late‐season activity precluded estimation for most subgroups. Conclusions 2022–23 late‐season outpatient influenza VE was not statistically significant. Genomic characterization may improve the identification of influenza viruses that circulate postinfluenza peak.

Background We estimated SARS‐CoV‐2 Delta‐ and Omicron‐specific effectiveness of two and three mRNA COVID‐19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS‐CoV‐2 testing within 10 days of illness onset. Using the test‐negative design, we compared the odds of receiving two or three mRNA COVID‐19 vaccine doses among SARS‐CoV‐2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS‐CoV‐2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS‐CoV‐2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two‐dose recipients and 96% (95% CI: 93% to 98%) for three‐dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two‐dose recipients and 62% (95% CI: 48% to 72%) among three‐dose recipients. Conclusions In this adult population, three mRNA COVID‐19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID‐19 in the United States. These findings support the recommendation for a third mRNA COVID‐19 vaccine dose.

Individuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50–80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold‐increases in antibody titer occurred among participants with lower pre‐vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status.

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.

Background: Youth from marginalized groups may be less likely to receive quality health care services. Adverse Childhood Experiences (ACEs) are known to impact long-term health, but it is unclear if there is a relationship between ACEs and receipt of Family Centered Care (FCC)—one indicator of high-quality health care. To assess this relationship, this study used a nationally representative sample of youth from the National Survey of Children’s Health 2016–2017 combined data set. Caregivers of children who had at least one health care visit in the last 12 months (sub-sample n = 63,662) were asked about five indicators of FCC including if they felt the provider: (1) spent enough time, (2) listened carefully, (3) helped family feel like a partner, (4) provided information requested, and (5) showed sensitivity to culture. Methods: Logistic regression analyses examined the association between ACE score and each FCC quality indicator, as well between ACEs score and the overall FCC dichotomous score. Results: ACE exposure did not significantly predict access to a health care visit in the past 12 months. However, children with higher rates of ACEs were significantly less likely to receive FCC. Other factors that significantly predicted lower FCC included child race and ethnicity, insurance type, language in the home, and access to a regular health provider. Conclusions: Providers and health systems must identify, implement, and advocate for effective trauma-informed and care coordination interventions that ensure quality health care services for vulnerable children and families.

Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011–12 through 2017–18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m 2 ), overweight (25–29 kg/m 2 ), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1—adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16–31, 46–54, and 44–57%, and in children from 29–34, 57–65, and 50–55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.