Diminished humoral and cellular responses to SARS-CoV-2 vaccines in patients with chronic lymphocytic leukemia.

Previous studies have demonstrated low rates of seroconversion to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with chronic lymphocytic leukemia (CLL). In this national collaboration of 11 cancer centers in the United States, we aimed to further characterize and understand vaccine-induced immune responses, including T-cell responses, and the impact of CLL therapeutics (#NCT04852822). Eligible patients were enrolled in 2 cohorts (1) at the time of initial vaccination and (2) at the time of booster vaccination. The serologic response rates (anti-S) from 210 patients in the initial vaccination cohort and 117 in the booster vaccination cohort were 56% (95% confidence interval [CI], 50-63) and 68% (95% CI, 60-77), respectively. Compared with patients not on therapy, those receiving B-cell-directed therapy were less likely to seroconvert (odds ratio [OR], 0.27; 95% CI, 0.15-0.49). Persistence of response was observed at 6 months; anti-S titers increased with the administration of booster vaccinations. In the initial vaccination cohort, positive correlations were observed between the quantitative serologic response and CD4 T-cell response for the Wuhan variant and, to a lesser degree, for the Omicron variant (Spearman P = 0.45 Wuhan; P = 0.25 Omicron). In the booster vaccination cohort, positive correlations were observed between serologic responses and CD4 T-cell responses for both variants (P = 0.58 Wuhan; P = 0.57 Omicron) and to a lesser degree for CD8 T-cell responses (P = 0.33 Wuhan; P = 0.22 Omicron). Although no deaths from coronavirus disease 2019 (COVID-19) have been reported after booster vaccinations, patients should use caution as newer variants emerge and escape vaccine-induced immunity. This trial was registered at www.clinicaltrials.gov as #NCT04852822.

The impact of B-cell-directed therapy on SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia.

Prior reports evaluating SARS-CoV-2 vaccine efficacy in chronic lymphocytic leukaemia (CLL) used semiquantitative measurements of anti-S to evaluate immunity; however, neutralization assays were used to assess functional immunity in the trials leading to vaccine approval. Here, we identified decreased rates of seroconversion in vaccinated CLL patients and lower anti-S levels compared to healthy controls. Notably, we demonstrated similar results with the Roche anti-S assay and neutralization activity. Durable responses were seen at six months; augmentation with boosters was possible in responding patients. Absence of normal B cells, frequently seen in patients receiving Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors, was a strong predictor of lack of seroconversion.

Risk Factors for Postpartum Emergency Department Visits in an Urban Population.

Objectives To identify risk factors associated with urban postpartum emergency department utilization. Methods This case-control study included 100 matched pairs of postpartum women who had delivered at a large, integrated urban medical system in Bronx, New York, in 2012-2013, with the cases having had an emergency department visit within 42 days of delivery. The cases, identified utilizing administrative and billing data, were matched 1:1 with controls by labor unit, delivery mode and date, excluding nonviable pregnancies. The controls did not have a known postpartum emergency department visit. Variables were abstracted from administrative data and chart review, and included demographics, antenatal/intrapartum/postpartum complications and neonatal intensive care unit admission. Factors associated with puerperal emergency department use were identified via univariate and multivariable analyses. Results Following conditional logistic regression, primiparity [54% vs. 32%, aOR 5.91, 95% CI 2.34-14.91], public insurance [70% vs. 56%, aOR 4.22, 95% CI 1.60-11.12], weekend delivery [30% vs. 26%, aOR 7.61, 95% CI 1.15-52.43] and delivery-related complications [47% vs. 28%, aOR 2.95, 95% CI 1.16-7.51] were associated with an increased risk of postpartum emergency department use, while women of younger ages (17-24 years old) were less likely to have postpartum emergency department use [aOR 0.23, 95% CI 0.07-0.74]. Univariate analysis of individual events within the composite variables showed an association between gestational hypertension/pre-eclampsia and postpartum emergency department use [28% vs. 13% OR 2.60, 95% CI 1.26-5.39]. Psychiatric history, social instability, preterm delivery/neonatal intensive care unit admission, pre-existing medical/antepartum conditions and prolonged postpartum stay were not associated. Conclusions for Practice Delivery-related complications, delivery timing, and certain sociodemographic factors are identifiable risk factors for increased postpartum emergency department utilization. These may be targeted for development of interventions improving puerperal care and potentially preventing emergency department visits, which are costly to the health system and disruptive to the lives of women and their families.

Correlation of Physical Exam Findings with Fever in Patients with Skin and Soft Tissue Infections.

INTRODUCTION: The objectives of this study were to determine the prevalence of fever in adult ED patients with skin and soft tissue infections (SSTI) and to determine which, if any, physical exam, radiograph and laboratory test findings were associated with fever. METHODS: We conducted a prospective, observational study at an urban county trauma center of adults who presented to the ED for evaluation of suspected SSTI. ED providers measured area of erythema and induration using a tape measure, and completed data sheets indicating comorbid conditions and the presence or absence of physical exam findings. Fever was defined as any recorded temperature ≥ 38°C during the first six hours of ED evaluation. RESULTS: Of the 734 patients enrolled, 96 (13.1%) had fever. Physical and laboratory exam findings associated with the presence of a fever in multivariable logistic regression were the area of erythema, particularly the largest quartile of area of erythema, 144 - 5,000 cm2, (odd ratio [OR] = 2.9; 95% confidence interval [CI] [1.6 - 5.2]) and leukocytosis (OR = 4.4, 95% CI [2.7 - 7.0]). Bullae, necrosis, streaks, adenopathy, and bone involvement on imaging were not associated with fever. CONCLUSION: Fever is uncommon in patients presenting to the ED for evaluation of suspected SSTI. Area of erythema and leukocytosis were associated with fever and should be considered in future decision rules for the evaluation and treatment of SSTI.