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The 2019–2020 Northern Hemisphere influenza vaccine includes antigens from 3c3.A H3N2 viruses; however, over half of circulating H3N2 viruses belong to subclade 3c2.A1b. Here, we analyze antibody responses elicited by the egg-adapted 3c3.A H3N2 vaccine strain in ferrets and humans. We find that this vaccine strain elicits antibodies that have reduced reactivity to a wild-type 3c3.A strain and very limited reactivity to 3c2.A strains, including the currently circulating 3c2.A1b strain. Vaccine mismatch and changes in antigenicity due to vaccine strain egg adaptation can affect seasonal influenza vaccine effectiveness. Here, Gouma et al. show that the egg-adapted 3c3.A H3N2 vaccine strain elicits antibodies with limited reactivity to a wildtype 3c3.A strain and currently circulating 3c2.A H3N2 strains.

Background For antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared with others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross‐sectional antibody‐derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season. Methods We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using focus reduction neutralization tests (FNRT) and enzyme‐linked lectin assays (ELLA). We estimated relative population‐average and age‐specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017–2018 season. Results The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age‐associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups. Conclusions This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza.

Influenza virus exposures in childhood can establish long-lived memory B cell responses that can be recalled later in life. Here, we complete a large serological survey to elucidate the specificity of antibodies against contemporary H3N2 viruses in differently aged individuals who were likely primed with different H3N2 strains in childhood. We find that most humans who were first infected in childhood with H3N2 viral strains from the 1960s and 1970s possess non-neutralizing antibodies against contemporary 3c2.A H3N2 viruses. We find that 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving many of them in a perpetual state of 3c2.A H3N2 viral susceptibility. Influenza exposure in early childhood can affect the immune response to distinct viral strains later in life. Here, Gouma et al. show that contemporary 3c2.A H3N2 virus infections boost non-neutralizing H3N2 antibodies in middle-aged individuals, potentially leaving them vulnerable to recurrent infections.

Purpose Precepting is an essential component of health professional educational programs, yet barriers exist for the recruitment and retention of preceptors. Our goal was to determine the incidence of precepting by physicians, physician assistants (PAs), and advanced practice registered nurses (APRNs) in Minnesota; whether the incidence of precepting varies by region or work setting; and to identify the factors that motivate or inhibit precepting. Method A survey study of physicians, PAs, and APRNs in Minnesota from February 9, 2023 through March 6, 2024. The survey was conducted at the time of health care professional (HCP) license renewal to determine the incidence, work setting, region, motivators, and inhibitors of healthcare precepting. The primary outcome was the incidence of precepting with other variables being work setting, region, motivators, and inhibitors. Results A total of 18,021 health care professionals were surveyed including 12,530 physicians, 3,073 PAs, and 2418 APRNs. The response rate was 97.4%. Across all professions, work settings, and regions the incidence of precepting was 67% (APRNs 70.7%; physicians 68.2%; PAs 61.2%). Precepting was more common in rural (73.6%) versus urban areas (66.9%); and at hospitals (75.6%) versus clinics (61.5%), long-term care (56.7%), or community settings (58.2%). The main motivators for precepting were intrinsic (because they enjoyed it and/or had a personal desire to serve the profession). For those that did not precept, the most common reasons were having no time in their schedule and not being paid to precept. Conclusions The majority of HCPs in Minnesota precept learners. The sites with the highest proportion of precepting were rural clinics and urban hospitals. Intrinsic factors were the major reason given for the decision to precept, with extrinsic factors playing a minor role in these decisions, but a major role for those that did not precept. Our results suggest organizational solutions could enhance the recruitment of preceptors. Keywords: shortage of preceptors; rural preceptors; clinical precepting and training.

Some studies suggest that recent common coronavirus (CCV) infections are associated with reduced COVID-19 severity upon SARS-CoV-2 infection. We completed serological assays using samples collected from health care workers to identify antibody types associated with SARS-CoV-2 protection and COVID-19 symptom duration. Rare SARS-CoV-2 cross-reactive antibodies elicited by past CCV infections were not associated with protection; however, the duration of symptoms following SARS-CoV-2 infections was significantly reduced in individuals with higher common betacoronavirus (βCoV) antibody titers. Since antibody titers decline over time after CCV infections, individuals in our cohort with higher βCoV antibody titers were more likely recently infected with common βCoVs compared with individuals with lower antibody titers. Therefore, our data suggest that recent βCoV infections potentially limit the duration of symptoms following SARS-CoV-2 infections through mechanisms that do not involve cross-reactive antibodies. Our data are consistent with the emerging hypothesis that cellular immune responses elicited by recent common βCoV infections transiently reduce symptom duration following SARS-CoV-2 infections.

To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system. Prospective observational cohort study open to adult employees at the Children's Hospital of Philadelphia, conducted April 20-December 17, 2020. Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity. In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03-3.68), Black race (HR, 2.70; 95% CI, 1.24-5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71-6.88) were associated with statistically significant increased risk for seropositivity. Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.

Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy. To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2. This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads. SARS-CoV-2 infection vs COVID-19 vaccination. IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines. A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination. This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

Here, we find that the egg-adapted H3N2 component of the 2019 Southern Hemisphere influenza vaccine elicits an antibody response in ferrets that is highly focused on antigenic site A of hemagglutinin. This is potentially problematic as most H3N2 viruses currently circulating in the Southern Hemisphere possess antigenic site A substitutions.

Cancer patients have high mortality from COVID-19, and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 cancer patients hospitalized for COVID-19, patients with hematologic cancers had higher mortality relative to solid cancers. In two additional cohorts, flow cytometric and serologic analyses demonstrated that solid cancer and non-cancer patients had a similar immune phenotype during acute COVID-19 whereas hematologic cancer patients had impairment of B cells and SARS-CoV-2-specific antibody responses. Despite the impaired humoral immunity and high mortality in hematologic cancer patients with COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Further, 77% of hematologic cancer patients had detectable SARS-CoV-2 specific T-cell responses. Thus, CD8 T cells may influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in hematologic cancer patients even in the setting of limited humoral responses.

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three \"immunotypes\" associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.