Changes in general and COVID-19 vaccine hesitancy among U.S. adults from 2021 to 2022.

INTRODUCTION: Understanding changes in vaccine hesitancy, overall and by sociodemographic characteristics, may highlight sub-populations for whom more intensive efforts are needed to increase vaccine uptake and confidence. METHODS: We analyzed data using the CDC's Research and Development Survey (RANDS), a nationally representative survey of U.S. adults ≥18 years, collected from 17 May 2021-30 June 2021 (n = 5,458) and 3 November 2022-12 December 2022 (n = 6,821). We assessed changes in vaccine hesitancy, changes in vaccine attitudes and attitudes, and factors associated with hesitancy toward both vaccines in general and COVID-19 vaccines among a nationally representative sample of U.S. adults. RESULTS: Although COVID-19 vaccination (≥1 dose) increased from 67.2% (2021) to 74.7% (2022), COVID-19 vaccine hesitancy increased from 40.7% to 44.6% during the same period. During the same period, hesitancy toward both COVID-19 vaccines and vaccines in general increased among those who were aged ≥65 years and who were non-Hispanic White. However, COVID-19 vaccine hesitancy decreased among non-Hispanic Black adults. Current or former smokers were more hesitant toward vaccines in general (aPR = 1.13, 95%CI: 1.03-1.24) and toward COVID-19 vaccines (aPR = 1.08, 95%CI: 1.01-1.16) compared to never smokers. Among adults who did not receive any COVID-19 vaccines, COVID-19 vaccine hesitancy increased from 86.6% in 2021 to 92.4% in 2022. Furthermore, belief in the overall social benefit of the COVID-19 vaccine decreased from 47.5% to 25.1%. CONCLUSION: This study highlights concerning trends in vaccine hesitancy and uptake of the COVID-19 and other recommended vaccines. We found that some high-risk groups (e.g. smokers) and population subgroups have become more vaccine hesitant, suggesting the need for improved and intensified strategies to increase vaccine confidence and uptake. Future research may focus on qualitative inquiry to understand specific concerns and determinants contributing to increased hesitancy among these groups to help inform interventions and communication campaigns to support vaccination.

COVID-19 vaccine hesitancy increased from 40.7% in 2021 to 44.6% in 2022.During the same period, hesitancy regarding both the COVID-19 vaccine and vaccines in general increased among those who were ≥65 years and non-Hispanic White while hesitancy toward COVID-19 vaccines decreased among non-Hispanic Black adults.Belief in the overall social benefit of the COVID-19 vaccine decreased from 47.5% to 25.1%, sug­gesting need to frame messaging on benefits such as protection from severe disease outcomes.

HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant.

Limited understanding of the immunopathogenesis of human herpesvirus 6B (HHV-6B) has prevented its acceptance as a pulmonary pathogen after hematopoietic cell transplant (HCT). In this prospective multicenter study of patients undergoing bronchoalveolar lavage (BAL) for pneumonia after allogeneic HCT, we test blood and BAL fluid (BALF) for HHV-6B DNA and mRNA transcripts associated with lytic infection and perform RNA-seq on paired blood. Among 116 participants, HHV-6B DNA is detected in 37% of BALs, 49% of which also have HHV-6B mRNA detection. We establish HHV-6B DNA viral load thresholds in BALF that are highly predictive of HHV-6B mRNA detection and associated with increased risk for overall mortality and death from respiratory failure. Participants with HHV-6B DNA in BALF exhibit distinct host gene expression signatures, notable for enriched interferon signaling pathways in participants clinically diagnosed with idiopathic pneumonia. These data implicate HHV-6B as a pulmonary pathogen after allogeneic HCT.

Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms.

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone ("CLAG-M") may result in higher remission rates than standard-dose cytarabine plus anthracycline ("7 + 3") but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06-2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed.

Reliability of Self-Sampling for Accurate Assessment of Respiratory Virus Viral and Immunologic Kinetics.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with flocked swabs. Using longitudinal home-based self-sampling, we demonstrate that nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics.

The SARS-CoV-2 pandemic demonstrates the need for accurate and convenient approaches to diagnose and therapeutically monitor respiratory viral infections. We demonstrated that self-sampling with foam swabs at home is well-tolerated and provides quantitative viral output concordant with flocked swabs. Nasal cytokine levels correlate and cluster according to immune cell of origin. Periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Nasal foam swab self-sampling at home provides a precise, mechanistic readout of respiratory virus shedding and local immune responses.

Human Herpesvirus 6B and Lower Respiratory Tract Disease After Hematopoietic Cell Transplantation.

PURPOSE: Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear. METHODS: We tested BALF for HHV-6B DNA using polymerase chain reaction in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992 to 2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B+ BALF with overall mortality, death from respiratory failure, and the effect of anti-HHV-6B antivirals on these outcomes. We used branched-chain RNA in situ hybridization to detect HHV-6 messenger RNA (U41 and U57 transcripts) in lung tissue. RESULTS: We detected HHV-6B+ BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B+ BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio [aHR], 2.18; 95% CI, 1.41-3.39) and death from respiratory failure (aHR, 2.50; 95% CI, 1.56-4.01) compared with subjects with HHV-6B- BALF. Subjects with HHV-6B+ BALF who received antivirals within 3 days pre-BAL had an approximately 1 log10 lower median HHV-6B BALF viral load, as well as a lower risk of overall mortality (aHR, 0.42; 95% CI, 0.16-1.10), compared with subjects with HHV-6B+ BALF not receiving antivirals. We detected intraparenchymal HHV-6 gene expression by RNA in situ hybridization in lung tissue in all three tested subjects with HHV-6B+ BALF and sufficient tissue RNA preservation. CONCLUSION: These data provide evidence that HHV-6B detection in BALF is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with LRTD. Definitive evidence of causation will require a randomized prevention or treatment trial.