Prior Influenza Research Articles

Influenza virus antibodies inhibit antigen-specific de novo B cell responses in mice.

Antibody responses to influenza vaccines tend to be focused on epitopes encountered during prior influenza exposures, with little production of de novo responses to novel epitopes. To examine the contribution of circulating antibodies to this phenomenon, we passively transferred a hemagglutinin (HA)-specific monoclonal antibody (mAb) into mice before immunizing with whole inactivated virions. The HA mAb inhibited de novo HA-specific antibodies, plasmablasts, germinal center B cells, and memory B cells, while responses to a second antigen in the vaccine, neuraminidase (NA), were uninhibited. The HA mAb potently inhibited de novo antibody responses against epitopes near the HA mAb binding site. The HA mAb also promoted IgG1 class switching, an effect that, unlike the inhibition of HA responses, relied on signaling through Fc-gamma receptors. These studies suggest that circulating antibodies inhibit de novo B cell responses in an antigen-specific manner, which likely contributes to differences in antibody specificities elicited during primary and secondary influenza virus exposures.IMPORTANCEMost humans are exposed to influenza viruses in childhood and then subsequently exposed to antigenically drifted influenza variants later in life. It is unclear if antibodies elicited by earlier influenza virus exposures impact immunity against new influenza virus strains. Here, we used a mouse model to investigate how an anti-hemagglutinin (HA) monoclonal antibody (mAb) affects de novo B cell and antibody responses to the protein targeted by the monoclonal antibody (HA) and a second protein not targeted by the monoclonal antibody [neuraminidase (NA)]. Collectively, our studies suggest that circulating anti-influenza virus antibodies can potently modulate the magnitude and specificity of antibody responses elicited by secondary influenza virus exposures.

Quality improvement initiative to reduce URI-associated antibiotic prescriptions among adult primary care providers

ImportanceDespite evidence that most upper respiratory infections (URIs) are due to viruses, antibiotics are frequently prescribed for this indication in the outpatient setting. Antibiotic stewardship strategies are needed to reduce...

Association Between Influenza Vaccination and SARS-CoV-2 Infection.

Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity. Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection. Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed. Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2%vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8%vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19). Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.

Potential pandemic risk of circulating swine H1N2 influenza viruses

Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans due to a potential lack of population level immunity. Here we describe a pipeline to characterize and triage influenza viruses for their pandemic risk and examine the pandemic potential of two widespread swine origin viruses. Our analysis reveals that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against a α-H1 clade strain (α-swH1N2) but do against a γ-H1 clade strain. The α-swH1N2 virus replicates efficiently in human airway cultures and exhibits phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09). Furthermore, α-swH1N2 is capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity show reduced α-swH1N2 viral shedding and less severe disease signs. Despite this, H1N1pdm09-immune ferrets that became infected via the air can still onward transmit α-swH1N2 with an efficiency of 50%. These results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness and pathology in animals with prior immunity.

Influenza and the risk of active tuberculosis occurrence among individuals with latent tuberculosis infection: A national cohort study in South Korea (2015–2020)

BackgroundInfluenza's potential impact on active tuberculosis (TB) development has been debated, with limited clinical evidence. To address this, we explored the association between influenza episodes and TB incidence in a national cohort of individuals with latent TB infection (LTBI). MethodsWe examined adults (≥20 years) diagnosed with LTBI between 2015 and 2020, using the Health Insurance Review and Assessment Service's national database in South Korea. We collected demographic data, comorbidities, and influenza episodes within 6 months before and after the initial LTBI diagnosis (prior vs. subsequent episode). We stratified the analysis into groups with and without TB preventive therapy (TPT). ResultsAmong 220,483 LTBI subjects, 49% received TPT, while 51% did not. The average age was 48.4 years, with 52% having comorbidities. A prior and subsequent influenza episode was identified in 3221 and 4580 individuals, respectively. Of these, 1159 (0.53%) developed incident TB over an average follow-up of 1.86 years. The incidence rates of TB were comparable between individuals with and without prior and/or subsequent influenza episodes in the TPT group, but 1.4 times higher in the non-TPT group for those with such episodes. Cox proportional-hazards regression analysis indicated that influenza was not a risk factor for incident TB in the TPT group. However, a subsequent influenza episode significantly increased TB risk in the non-TPT group (hazard ratio: 1.648 [95% CI, 1.053–2.580]). ConclusionsIn individuals with LTBI not receiving TPT, experiencing an influenza episode may elevate the risk of developing active TB.

Assessment of the antigenic evolution of a clade 6B.1 human H1N1pdm influenza virus revealed differences between ferret and human convalescent sera

Influenza viruses continually acquire mutations in the antigenic epitopes of their major viral antigen, the surface glycoprotein haemagglutinin (HA), allowing evasion from immunity in humans induced upon prior influenza virus infections or vaccinations. Consequently, the influenza strains used for vaccine production must be updated frequently. To better understand the antigenic evolution of influenza viruses, we introduced random mutations into the HA head region (where the immunodominant epitopes are located) of a pandemic H1N1 (H1N1pdm) virus from 2015 and incubated it with various human sera collected in 2015-2016. Mutants not neutralized by the human sera were sequenced and further characterized for their haemagglutination inhibition (HI) titers with human sera and with ferret sera raised to H1N1pdm viruses from 2009 to2015. The largest antigenic changes were conferred by mutations at HA amino acid position 187; interestingly, these antigenic changes were recognized by human, but not by ferret serum. H1N1pdm viruses with amino acid changes at position 187 were very rare until the end of 2018, but have become more frequent since; in fact, the D187A amino acid change is one of the defining changes of clade 6B.1A.5a.1 viruses, which emerged in2019. Our findings indicate that amino acid substitutions in H1N1pdm epitopes may be recognized by human sera, but not by homologous ferret sera. This project was supported by funding from the NIAID-funded Center for Research on Influenza Pathogenesis (CRIP, HHSN272201400008C).

Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Characteristics and determinants of seasonal influenza vaccination in Manitoba, Canada: A population-wide record-linkage study

BackgroundSeasonal influenza vaccine (SIV) uptake (receipt of vaccine) in Manitoba, Canada is consistently low notwithstanding vaccine availability and free-of-charge vaccination. Despite, there is a lack of published evidence on the determinants of uptake of the vaccine. We sought to assess the association between SIV uptake and certain population and primary care physician (PCP) characteristics in Manitoba. MethodsWe conducted a longitudinal study utilizing Manitoba administrative health databases. We summarized SIV uptake from 2000/01–2019/20 influenza seasons across subpopulations defined by socioeconomic, health-related and PCP characteristics. Utilizing multivariable generalized estimating equation logistic regression models, we assessed the association between SIV uptake and the socioeconomic, health-related and PCP characteristics, stratified by age group (<5-, 5–17-, 18–44-, 45–64-, ≥65-year-olds) and sex. Results are adjusted odds ratios with associated 95 % confidence intervals. ResultsSIV uptake percentage increased over time with 4.4 %, 13.1 %, 17.5 % and 21.7 % of < 5-year-olds, 2 %, 4.9 %, 9.7 % and 13.1 % of 5–17-year-olds, 5.4 %, 8.8 %, 10.7 % and 13.5 % of 18–44-year-olds, 16.8 %, 21.3 %, 23.6 % and 24.6 % of 45–64-year-olds receiving the SIV in 2000–2004, 2005–2009, 2010–2014 and 2015–2019, respectively. There was a decline among ≥ 65-year-olds from 58.5 % to 53.5 %. We observed a similar pattern across subpopulations. There were significantly increased odds of SIV uptake among females within the age groups ≥ 18 years, in higher income quintiles, mostly with increased contact with a PCP/hospitalization within age groups ≥ 18 years, among those who had older or female PCPs (the opposite observation among ≥ 65-year-olds) and whose PCP administered at least one SIV in prior influenza season. These observations were largely consistent irrespective of sex. ConclusionSIV uptake in Manitoba appears to increase with age, and many socioeconomic, health-related and PCP characteristics appear to be associated with it. These findings may inform targeted vaccination programs to optimize influenza vaccination in Manitoba and similar Canadian jurisdictions.

Intracellular Streptococcus pneumoniae develops enhanced fluoroquinolone persistence during influenza A coinfection.

Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.

Risk Factors for Not Completing a 2-Dose Primary Series of Messenger RNA COVID-19 Vaccination in a Large Health Care System in Southern California: Retrospective Cohort Study.

COVID-19 vaccination is crucial in combating the COVID-19 pandemic. Messenger RNA COVID-19 vaccines were initially authorized as a 2-dose primary series and have been widely used in the United States; completing the 2-dose primary series offers protection against infection, severe illness, and death. Understanding the risk factors for not completing the 2-dose primary series is critical to evaluate COVID-19 vaccination programs and promote completion of the 2-dose primary series. This study examined potential risk factors for not completing a 2-dose primary series of mRNA COVID-19 vaccination. We conducted a retrospective cohort study among members aged ≥18 years from a large integrated health care system, Kaiser Permanente Southern California, from December 14, 2020, to June 30, 2022. Noncompletion of the 2-dose primary series was defined as not completing the second dose within 6 months after receipt of the first dose. Crude noncompletion rates were estimated overall and by demographic characteristics, health care use patterns, comorbidity, and community-level socioeconomic factors. A Poisson regression model was fit to examine associations of individual-level and community-level risk factors with noncompletion of the 2-dose primary series. Among 2.5 million recipients of ≥1 dose of mRNA COVID-19 vaccines, 3.3% (n=81,202) did not complete the second dose within 6 months. Members aged 25-44 years, 65-74 years, and ≥75 years were less likely to not complete the 2-dose primary series than those aged 18-24 years, while members aged 45-64 years were more likely to not complete the 2-dose primary series (adjusted risk ratio [aRR] 1.13, 95% CI 1.10-1.15). Male sex was associated with a higher risk of noncompletion (aRR 1.17, 95% CI 1.15-1.19). Hispanic and non-Hispanic Black race/ethnicity were associated with a lower risk of noncompletion (range aRR 0.78-0.91). Having Medicaid and prior influenza vaccination were associated with a higher risk of noncompletion. Having SARS-CoV-2 infection, experiencing an adverse event, or having an inpatient and emergency department visit during the minimum recommended dose intervals were associated with a higher risk of not completing the 2-dose primary series (aRR 1.98, 95% CI 1.85-2.12; 1.99, 95% CI 1.43-2.76; and 1.85, 95% CI 1.77-1.93, respectively). Those who received the first dose after June 30, 2021, were more likely to not complete the 2-dose primary series within 6 months of receipt of the first dose. Despite limitations such as being a single-site study and the inability to consider social factors such as employment and vaccine attitudes, our study identified several risk factors for not completing a 2-dose primary series of mRNA vaccination, including being male; having Medicaid coverage; and experiencing SARS-CoV-2 infection, adverse events, or inpatient and emergency department visits during the minimum recommended dose intervals. These findings can inform future efforts in developing effective strategies to enhance vaccination coverage and improve the completion rate of necessary doses.

Co-infection of mice with SARS-CoV-2 and Mycobacterium tuberculosis limits early viral replication but does not affect mycobacterial loads.

Viral co-infections have been implicated in worsening tuberculosis (TB) and during the COVID-19 pandemic, the global rate of TB-related deaths has increased for the first time in over a decade. We and others have previously shown that a resolved prior or concurrent influenza A virus infection in Mycobacterium tuberculosis (Mtb)-infected mice resulted in increased pulmonary bacterial burden, partly through type I interferon (IFN-I)-dependent mechanisms. Here we investigated whether SARS-CoV-2 (SCV2) co-infection could also negatively affect bacterial control of Mtb. Importantly, we found that K18-hACE2 transgenic mice infected with SCV2 one month before, or months after aerosol Mtb exposure did not display exacerbated Mtb infection-associated pathology, weight loss, nor did they have increased pulmonary bacterial loads. However, pre-existing Mtb infection at the time of exposure to the ancestral SCV2 strain in infected K18-hACE2 transgenic mice or the beta variant (B.1.351) in WT C57Bl/6 mice significantly limited early SCV2 replication in the lung. Mtb-driven protection against SCV2 increased with higher bacterial doses and did not require IFN-I, TLR2 or TLR9 signaling. These data suggest that SCV2 co-infection does not exacerbate Mtb infection in mice, but rather the inflammatory response generated by Mtb infection in the lungs at the time of SCV2 exposure restricts viral replication.

Disparities in Mpox Vaccination Among Priority Populations During the 2022 Outbreak.

The 2022 mpox outbreak disproportionately affected men who have sex with men and persons living with HIV (PLWH). A 2-dose mpox vaccine series was deployed in mid-2022. Structural racism and insurance status may have affected equitable vaccination. We defined 3 cohorts: PLWH with at least 1 clinic visit between 1 July 2021 and 1 July 2022 (n = 2066), HIV preexposure prophylaxis (PrEP) recipients as of 1 January 2022 (n = 262), and all mpox-vaccinated patients in our health system between 1 July 2022 and 30 November 2022 (n = 807). We identified patients with prior diagnosed sexually transmitted infections (STIs) as having a positive test result for gonorrhea, chlamydia, or syphilis between 1 July 2021-1 July 2022. The primary outcome was receipt of at least 1 dose of mpox vaccine. We identified 224 (10.8%) PLWH and 50 (19.0%) PrEP patients who received at least 1 dose of mpox vaccine. Among PLWH, White race (odds ratio [OR], 1.55; 95% CI, 1.11-2.16), private insurance (OR, 1.83; 95% CI, 1.01-3.34), prior STI (OR, 3.04; 95% CI, 2.16-4.27), prior COVID-19 vaccination (OR, 3.17; 95% CI, 1.93-5.20), and prior influenza vaccination (OR, 1.42; 95% CI, 1.30-1.96) independently predicted mpox vaccination. Within the PrEP cohort, prior COVID-19 vaccination and seasonal influenza vaccination predicted mpox vaccination. Uninsured patients were vaccinated later in the outbreak than patients with private insurance (median time to vaccination, 41 days in the privately insured group vs 83 days in the uninsured group; P < .0001). Race, insurance status, prior STI, and previous receipt of other vaccines influenced uptake of mpox vaccine. Addressing health disparities and vaccine acceptance will be essential in improving future outbreak response.

Influenza vaccine uptake among children and older adults in China: a secondary analysis of a quasi-experimental study

BackgroundInfluenza vaccination is the key to prevent influenza-related disease, especially among high-risk populations. However, influenza vaccine uptake in China is low. This secondary analysis of a quasi-experimental trial aimed to understand factors associated with influenza vaccine uptake among children and older people stratified by funding context.MethodsA total of 225 children (aged 0.5-8 years) and 225 older people (aged 60 years or above) were recruited from three clinics (rural, suburban and urban) in Guangdong Province. Participants were allocated into two groups based on funding contexts: a self-paid group (N = 150, 75 children and 75 older adults) in which participants paid full price for their vaccination; and a subsidized group (N = 300, 150 children and 150 older adults) in which varying levels of financial support was provided. Univariate and multivariable logistic regressions were conducted stratified by funding contexts.ResultsOverall, 75.0% (225/300) of participants in the subsidized group and 36.7% (55/150) in the self-paid group got vaccinated. Older adults had lower vaccination rates than children in both funding groups, while both age groups showed much higher uptake in the subsidized group than in the self-paid group (aOR = 5.96, 95% CI: 3.77–9.42, p = 0.001). In the self-paid group, having prior influenza vaccination history of children (aOR:2.61, 95%CI: 1.06–6.42) or older people (aOR:4.76, 95%CI: 1.08–20.90) was associated with increased influenza vaccine uptake compared to those who had no prior vaccination experiences in the family. While in the subsidized group, participants who got married or lived with partners (aOR = 0.32, 0.10–0.98) had lower vaccination uptake than single ones. Trust in providers’ advice (aOR = 4.95, 95%CI:1.99, 12.43), perceived effectiveness of the vaccine (aOR: 12.18, 95%CI: 5.21–28.50), and experienced influenza-like illnesses in the family in the past year (aOR = 46.52, 4.10, 533.78) were associated with higher vaccine uptake.ConclusionsOlder people had suboptimal vaccine uptake compared to children in both contexts and need more attention to enhance influenza vaccination. Tailoring interventions to different vaccine funding contexts may help improve influenza vaccination: In self-paid context, motivating people to accept their first ever influenza vaccination may be a promising strategy. In subsidized context, improving public confidence in vaccine effectiveness and providers’ advice would be useful.

Evaluation of behavioral economic strategies to raise influenza vaccination rates across a health system: Results from a randomized clinical trial

Influenza vaccination rates are low. Working with a large US health system, we evaluated three health system-wide interventions using the electronic health record's patient portal to improve influenza vaccination rates. We performed a two-arm RCT with a nested factorial design within the treatment arm, randomizing patients to usual-care control (no portal interventions) or to one or more portal interventions. We included all patients within this health system during the 2020–2021 influenza vaccination season, which overlapped with the COVID-19 pandemic. Through the patient portal, we simultaneously tested: pre-commitment messages (sent September 2020, asking patients to commit to a vaccination); monthly portal reminders (October – December 2020), direct appointment scheduling (patients could self-schedule influenza vaccination at multiple sites); and pre-appointment reminder messages (sent before scheduled primary care appointments, reminding patients about influenza vaccination). The main outcome measure was receipt of influenza vaccine (10/01/2020–03/31/2021). We randomized 213,773 patients (196,070 adults ≥18 years, 17,703 children). Influenza vaccination rates overall were low (39.0%). Vaccination rates for study arms did not differ: Control (38.9%), pre-commitment vs no pre-commitment (39.2%/38.9%), direct appointment scheduling yes/no (39.1%/39.1%), pre-appointment reminders yes/no (39.1%/39.1%); p > 0.017 for all comparisons (p value cut-off adjusted for multiple comparisons). After adjusting for age, gender, insurance, race, ethnicity, and prior influenza vaccination, none of the interventions increased vaccination rates. We conclude that patient portal interventions to remind patients to receive influenza vaccine during the COVID-19 pandemic did not raise influenza immunization rates. More intensive or tailored interventions are needed beyond portal innovations to increase influenza vaccination.

Evaluation of a team-based quality improvement initiative for influenza vaccination in an underserved population.

Influenza vaccine is the most effective way to prevent influenza. However, low vaccination rates continue especially in underserved populations. To increase influenza vaccinations in an underserved population and to evaluate the impact of influenza vaccinations compared to previous year influenza vaccinations. Federally-Qualified Health care Center for the Homeless, Richmond, Virginia PRACTICE INNOVATION: Team-based quality improvement initiative led by a pharmacist champion. Before and after evaluation of the quality improvement initiative was conducted by comparing the total number of vaccines administered to those administered the previous year. Influenza vaccinations increased by 42% over the prior influenza vaccination season (1269 vs. 895), respectively. From a population perspective, 31% of patients received an influenza vaccine in 2019-20 and 48% in 2020-21. During the 2019-20 influenza vaccine season, the majority of patients vaccinated were female 56% versus 50.9% in 2020-21. The average age increased from 2019-20 to 2020-21, 37.62 years of age versus 42.71 years of age, respectively. A team-based quality improvement initiative was successful in improving our influenza vaccination program for adults and has served as a foundation for the delivery of other vaccines. Lessons learned were used to implement a COVID-19 vaccine program.

Willingness of Saudi Adults to Receive a COVID-19 Vaccine Booster Dose

Background: COVID-19 vaccine booster dose hesitancy amongst the Saudi Arabia population is a concern. The objectives of the study were to explore the Saudi public’s willingness to receive a COVID-19 vaccine booster dose and identify the factors affecting their willingness. Methods: From December 2021 to March 2022, an online cross-sectional survey using an anonymous, structured, and self-administered questionnaire was conducted among members of the Saudi public aged ≥18 years who did not receive a COVID-19 vaccine booster dose. Results: Of the 2101 respondents, 86.8% expressed a willingness to receive a COVID-19 vaccine booster dose. Multiple logistic regression analysis showed that age (18 to 25 years) (adjusted odds ratio [aOR] = 2.54; 95% confidence interval [95% CI] = 1.14–5.74), being single (aOR = 2.85; 95% Cl = 1.42–5.72), and prior receipt of an influenza vaccine (aOR = 2.45; 95% Cl = 1.80–3.34) were significantly associated with participants’ willingness to receive the COVID-19 vaccine booster dose. Having a bachelor’s degree or above (aOR = 0.95; 95% CI = 0.81–0.99) and not following COVID-19 news (aOR = 0.70; 95% CI = 0.52–0.89) were associated with a significant likelihood of having no intention to receive the COVID-19 vaccine boosters. Conclusions: Most Saudi people were willing to have the COVID-19 vaccine booster dose, with age and prior influenza vaccination as the predictors; paradoxically, a university-level qualification was a barrier.

Active immunization with Pseudomonas aeruginosa vaccine protects mice from secondary Pseudomonas aeruginosa challenge post-influenza virus infection.

Influenza virus infection complicated by secondary bacterial pneumonia contributes significantly to death during seasonal or pandemic influenza. Secondary infection of Pseudomonas aeruginosa (P. aeruginosa) in influenza virus-infected patients contributes to morbidity and mortality. Mice were first infected with PR8 influenza virus, followed by a secondary infection of P. aeruginosa. Body weights and survival rate of mice was monitored daily over 20 days. Bronchoalveolar lavage fluids (BALFs) and lung homogenates were harvested for measuring bacterial titers. Lung tissue section slides were stained with hematoxylin and eosin for microscopic observation. After vaccination with inactivated P. aeruginosa cells or recombinant PcrV protein, the mice were subjected to PR8 influenza virus infection followed by a secondary infection of a P. aeruginosa. The inhibition against P. aeruginosa of serum was evaluated by detecting the growth of P. aeruginosa in broth containing diluted sera. The prior influenza infection greatly enhanced the susceptibility to secondary infection of P. aeruginosa and increased morbidity and mortality in mice. Active immunization with inactivated P. aeruginosa cells could protect mice from secondary P. aeruginosa challenge in influenza virus infected mice. To develop an effective P. aeruginosa vaccine might be a promising strategy to decrease the threat of secondary P. aeruginosa infection in influenza patients.

Characterization of COVID-19 Vaccine Hesitancy Among Essential Workforce Members of a Large Safety Net Urban Medical Center.

Vaccine hesitancy among essential workers remains a significant public health challenge. We examined psychological constructs of perceived susceptibility, threat, and self-efficacy and their associations with COVID-19 vaccine hesitancy among a racially and ethnically diverse essential workforce population. We performed a cross-sectional survey of essential workers from September-December 2020 at a large Los Angeles safety-net medical center as part of a program offering free COVID-19 serology testing. Program participants completed a standardized survey at the time of phlebotomy. Hierarchical logistic regression was utilized to determine factors independently associated with vaccine hesitancy. Among 1327 persons who had serology testing, 1235 (93%) completed the survey. Of these, 958 (78%) were healthcare workers. Based on expressed intent, 22% were vaccine-hesitant 78% were vaccine acceptors. In our multivariate model, vaccine hesitancy was associated with female gender [aOR = 2.09; 95% CI (1.44-3.05)], African American race [aOR = 4.32; (2.16-8.62)], LatinX ethnicity [aOR = 2.47; 95% CI (1.51-4.05)] and history of not/sometimes receiving influenza vaccination [aOR = 4.39; 95% CI (2.98-6.48)]. Compared to nurses, vaccine hesitancy was lower among physicians [aOR = 0.09; 95% CI (0.04-0.23)], non-nursing/non-physician healthcare workers [aOR = 0.55; 95% CI (0.33-0.92)], and non-healthcare care workers [aOR = 0.53; 95% CI (0.36-0.78)]. Among a racially/ethnically diverse group of safety net medical center essential workers, COVID-19 vaccine hesitancy was associated with racial/ethnic minority groups, employment type, and prior influenza vaccination hesitancy. Interestingly, we found no association with the Health Belief Model construct measures of perceived susceptibility, threat, and self-efficacy. Psychological constructs not assessed may be drivers of vaccine hesitancy in our population.

1967. Receipt of Influenza Vaccination as Predictor of COVID-19 Vaccination among United States Veterans

Abstract Background Vaccine hesitancy has been a major barrier during the COVID-19 pandemic. Surveys administered to assess vaccine acceptance have indicated several factors associated with individual’s intention to receive COVID-19 vaccination, including risk perception, concern for side effects, political orientation, male sex, and having received an influenza (flu) vaccine. However, it is unknown whether these factors predict receipt of vaccination. We sought to determine factors that predicted COVID-19 vaccination in the Veterans Health Administration (VHA). Methods We extracted COVID-19 vaccine status among Veterans with any VHA outpatient or inpatient visit from 12/01/2020 - 12/01/2021 from the VHA Corporate Data Warehouse. To ensure participants were engaged in ongoing VHA care, deceased individuals, and those with no visits in the prior year were excluded. We estimated association of proportion of years of VHA care in which influenza vaccine was received in the preceding 5 years with COVID-19 vaccination by logistic regression, adjusting for age, sex, and rurality of home address. Results We identified 5,700,590 Veterans with outpatient/inpatient visits during the study period, with median age 66 years, of whom 5,131,617 (90%) were male. A total of 3,704,617 (65%) received at least 1 COVID-19 vaccination. Individuals who received influenza vaccination during each year in care had more than 4 times the odds of receiving COVID-19 vaccination than those who never received influenza vaccination. (Table 1). Age groups 50-64 years had twice the odds, and years 65-74 and over 75 had 3 times the odds of receiving COVID-19 vaccination versus those 18-49, while Veterans living in rural and highly rural areas had lower odds of receiving COVID-19 vaccination versus those in urban areas. Table 1.Multiple logistic regression analysis of predictors of COVID-19 vaccination among Veterans cared for in the Veterans Health Administration, December 2020 – December 2021. N=5,700,590 Abbreviations: aOR = Adjusted Odds Ratio, CI = Confidence Interval. 1 Proportion of years in care influenza vaccine received was calculated by dividing the total number of years a Veteran received influenza vaccine by the total number years the Veteran received care for the 5 years prior to the study time period. 2 VHA uses the Rural Urban Commuting Areas (RUCA) system to define rurality (RURAL VETERANS - Office of Rural Health (va.gov) Conclusion Influenza vaccination on a regular basis (i.e., annually) was strongly linked to receipt of COVID-19 vaccination, indicating that prior influenza vaccine acceptance predicted COVID-19 vaccination. Public health efforts to reduce vaccine hesitancy (including targeted messaging to younger individuals, and those in rural areas) are important to increase vaccine acceptance in preparation for the next pandemic, as well as to decrease annual disease burden. Disclosures All Authors: No reported disclosures.

DYNAMIC cohort study evaluating metabolic predictors of influenza vaccine immune response in older adults

Immunosenescence (age-related immune dysfunction) and inflamm-aging contribute to suboptimal immune responses in older adults to standard-dose influenza vaccines, which may be exacerbated in those with metabolic co-morbidities. We sought to investigate metabolic factors/predictors of influenza vaccine immune response in an older adult (age ≥65 years) cohort in Singapore, where influenza typically circulates year-round. The primary outcome for the DYNAMIC prospective cohort study was haemagglutination-inhibition titer (HAI) response to each of the trivalent inactivated influenza vaccine strains at day 28 (D28) compared to baseline (D0), as assessed by seroconversion and D28/D0 log2 HAI fold rise. Baseline blood samples were tested for total Vitamin D (25-(OH) D) levels. We enrolled 234 participants in June–Dec 2017. Two hundred twenty completed all study visits. The median age was 71 [IQR 68–75] years, 67 (30.5%) had diabetes mellitus (DM), and the median BMI was 24.9 [IQR 22.2–27.8] kg/m2. Median baseline totals 25-(OH) D was 29 [IQR: 21–29] ng/ml. Age, DM, obesity, and baseline 25-(OH) D were not associated with HAI fold rise in multivariable analysis. More recent prior influenza vaccination and higher baseline HAI titers were associated with lower HAI fold rise for influenza A/HK/H3N2. Physical activity was associated with a higher HAI fold rise for influenza A/HK/H3N2 in a dose-response relationship (p-test for trend = 0.015). Older adults with well-controlled metabolic co-morbidities retain HAI response to the influenza vaccine, and physical activity had a beneficial effect on immune response, particularly for influenza A/HK/H3N2.