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.

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.