Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies. We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies. A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive seroconversion. Through a predesigned survey, patients also self-reported side effects from each dose of vaccination. Seroconversion on vaccination was seen in 6/12 (50%) patients with CLL, 7/11 (63.6%) patients with NHL, 9/10 (90%) patients with MM, and 17/20 (85%) patients with solid organ malignancy. Only 6 of the 14 (42.8%) patients currently on or with previous history of rituximab use seroconverted. Injection site soreness was the most reported side effect. The only severe side effect occurred in a patient with solid organ malignancy who developed Parsonage-Turner syndrome. Patients with CLL and NHL appear less likely to respond to vaccination against COVID-19 in contrast to patients with MM or solid organ malignancies. Previous treatment with rituximab is a possible risk factor for suboptimal response to vaccination. These data highlight the importance of continuing risk mitigation strategies against COVID-19 in individuals with hematologic malignancy, particularly those with CLL or on treatment with rituximab

Patient Satisfaction with In-Person, Video, and Telephone Allergy/Immunology Evaluations During the COVID-19 Pandemic

Background: The SarsCoV2, novel coronavirus (COVID-19) pandemic necessitated a rapid transition from in-person evaluations to remote delivery of care, including both video and telephone visits, in allergy/immunology practices. Objective: To evaluate patient satisfaction, patient and physician impression of encounter completeness, and reimbursement between in-person, video, and telephone encounters. This study also assessed factors influencing patient satisfaction, perception of completeness, and choice of future evaluation type. Methods: This was a prospective study of all encounters at a health care-system owned practice. Encounter type, encounter modality, patient demographics, primary diagnoses, reimbursement data, and physician assessment of encounter completeness were tracked. Patient satisfaction was assessed via standardized questions. Results: There were 447 encounters, with 303 in-person (67.8%), 98 video (21.9%), and 46 telephone (10.3%). Patient satisfaction data was obtained from 251 patients. There was similar patient satisfaction among all encounter modalities. Both patients and physicians were more likely to deem an in-person encounter as complete. Physicians were more likely to report an in-person encounter to be complete for food allergy (P \u3c .001) and chronic rhinitis (P = .001) compared with video or telephone, whereas patients reported in-person encounters for food allergy to be complete compared with other modalities (P = .002). Patients reported that future encounter types should depend on the clinical situation. Conclusions: There was similar patient satisfaction with in-person, video, and telephone encounters in an allergy/immunology practice during the COVID-19 pandemic. Chronic rhinitis and food allergy are more likely to call for an in-person evaluation. New patient visits are likely to be the highest yield to focus on for in-person evaluations

Efficacy of epinephrine and diphenhydramine rinses in decreasing local reactions to subcutaneous aeroallergen immunotherapy

Background: Although local reactions (LR) to subcutaneous immunotherapy (SCIT) occur in 26-86% of patients, there are no well-studied strategies to manage LRs. Objective: To complete a prospective, randomized, single-blind, controlled trial that compared pre-rinsing SCIT syringes with diphenhydramine, epinephrine, or placebo in patients who were receiving aeroallergen SCIT and experiencing LRs despite pretreatment with an antihistamine. Methods: Patients ages ≽5 years who were receiving aeroallergen SCIT per a conventional dosing schedule and who were experiencing LRs despite premedicating with an oral antihistamine were randomized to diphenhydramine, epinephrine, or placebo rinse, and were followed up for three subsequent visits. At each visit, the patients were asked (yes or no) if LRs improved. Results: A total of 490 patients were enrolled in the study. Seventy-four of the 490 patients (15.1%) experienced an LR despite pretreatment with an oral antihistamine and were randomized into an intervention group. At visit 1, an epinephrine rinse was strongly associated with decreasing LR compared with both diphenhydramine rinse and placebo (p \u3c 0.001). There was no difference among the intervention groups at visits 2 and 3. In patients who reported a consistent outcome at all three visits, the epinephrine rinse was significantly associated with a decrease in LR compared with both diphenhydramine rinse and placebo rinse (p = 0.05). Conclusion: In patients who received aeroallergen SCIT per a conventional dosing schedule, an epinephrine rinse significantly decreased LR at the first visit, and also within a population that reported a consistent outcome at all three study visits. In patients already premedicating with an oral antihistamine, adding an epinephrine rinse is a safe and effective strategy to decrease LRs to aeroallergen SCIT

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab

BACKGROUND: Rituximab is an anti-CD20 chimeric antibody used to treat autoimmune conditions and B cell neoplasms. We characterized immunoglobulin (Ig) levels and vaccine responses in rituximab-treated B cell non-Hodgkin lymphoma (NHL) patients. Patients with impaired vaccine responses were offered therapy with 20% subcutaneous (subq) Ig. PATIENTS AND METHODS: Patients with a biopsy-proven diagnosis of B cell NHL who had received rituximab within the past 24 months were eligible for the study and underwent the following immune evaluation: serum IgG, IgM, IgA, IgE, T/B cell lymphocyte panel, and pre/post vaccine IgG titers to diphtheria, tetanus, and streptococcus pneumoniae. Patients were vaccinated with tetanus, diphtheria and pneumococcal polysaccharide vaccine. Patients with abnormal vaccine responses were offered prophylactic subq Ig for 52 weeks. RESULTS: Fifteen patients with NHL were enrolled in the study. The median IgG was 628 mg/dL [interquartile range, 489-718 mg/dL]. Three (20%) of 15 patients responded to diphtheria vaccination, 1 (6.7%) of 15 responded to tetanus vaccination, and 3 (20%) of 15 responded to vaccination to streptococcus pneumoniae. Thirteen (86.7%) of 15 met criteria for humoral immunodeficiency. Ten patients received subq Ig, and experienced a significant increase in serum IgG (P = .008). There were no serious adverse events, and there was a decrease in nonneutropenic infections while on subq Ig therapy. CONCLUSIONS: Patients with NHL treated with rituximab may have significant humoral immunodeficiency as defined by abnormal vaccine responses even in the setting of relatively normal IgG levels. For these patients, subq Ig replacement therapy is well-tolerated and efficacious in improving serum IgG, and may decrease reliance on antibiotics for the treatment of nonneutropenic infections

Dupilumab as Add-on Therapy for Chronic Rhinosinusitis With Nasal Polyposis in Aspirin Exacerbated Respiratory Disease

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) affects 7% of asthmatics. Usual therapies are inadequate for asthma and/or nasal polyposis, leading to decreased quality of life. OBJECTIVE: Our objective was to evaluate the efficacy of dupilumab in AERD patients with uncontrolled, chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODS: Patients 18 years and older with a physician diagnosis of AERD and sino-nasal outcome test 22 (SNOT 22) score ≥19 despite standard medical therapy were eligible for the study. Patients received one month of placebo dosing, followed by 6 months of dupilumab. Patients were blinded to the order of therapy. Wilcoxon-paired rank sum test was used to compare study outcomes at baseline and the completion of the study. RESULTS: Ten patients completed the study. The median baseline SNOT 22 score improved from 46 [IQR: 34 to 64.8] to 9.5 [IQR: 2.5 to 19] after 6 months of therapy (p = 0.0050). The median baseline Lund MacKay score improved from 21.5 [IQR: 17 to 23.3] to 4 [IQR: 1.2 to 6] after 6 months of therapy (p = 0.0050). There was also improvement in the following secondary outcomes: asthma control test (ACT), mini asthma quality of life questionnaire (AQLQ), and University of Pennsylvania Smell Identification test (UPSIT). Exhaled nitric oxide (FeNO), total serum IgE, 24-hour urinary leukotriene E, and serum thymus and activation regulated cytokine (TARC) also decreased. There were no significant study-related adverse events. CONCLUSION: Dupilumab was highly effective as add-on therapy for CRSwNP in AERD, improving patient-reported outcomes, sinus opacification, and markers of T2 inflammation

Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic lymphocytic leukemia

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population. PATIENTS AND METHODS: Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks. RESULTS: Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG. CONCLUSIONS: Patients with CLL demonstrate humoral immunodeficiency despite IgG \u3e 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs. CLINICAL TRIALS REGISTRATION: NCT03730129

Screening for humoral immunodeficiency in patients with community-acquired pneumonia

BACKGROUND: Immunodeficiency is an underrecognized risk factor for infections, such as community-acquired pneumonia (CAP). OBJECTIVE: We evaluated patients admitted with CAP for humoral immunodeficiency. DESIGN: Prospective cohort study SETTING: Inpatients PATIENTS, INTERVENTION, AND MEASUREMENTS: We enrolled 100 consecutive patients admitted with a diagnosis of CAP from February 2017 to April 2017. Serum IgG, IgM, IgA, and IgE levels were obtained within the first 24 hours of admission. CURB-65 score and length of hospital stay were calculated. The Wilcoxon rank-sum test, Kruskal-Wallis test, and simple linear regression analysis were used in data analysis. RESULTS: The prevalence of hypogammaglobinemia in patients with CAP was 38% (95% CI: 28.47% to 48.25%). Twenty-seven of 100 patients had IgG hypogammaglobinemia (median: 598 mg/dL, IQ range: 459-654), 23 of 100 had IgM hypogammaglobinemia (median: 38 mg/dL, IQ range: 25-43), and 6 of 100 had IgA hypogammaglobinemia (median: 36 mg/dL, IQ range: 18-50). The median hospital length of stay for patients with IgG hypogammaglobinemia was significantly higher when compared to patients with normal IgG levels (five days, IQ range [3-10] vs three days, IQ range [2-5], P = .0085). Fourteen patients underwent further immune evaluation, resulting in one diagnosis of multiple myeloma, three patients diagnosed with specific antibody deficiency, and one patient diagnosed with selective IgA deficiency. CONCLUSION: There is a high prevalence of hypogammaglobinemia in patients hospitalized with CAP, with IgG and IgM being the most commonly affected classes. IgG hypogammaglobinemia was associated with an increased length of hospitalization. Screening immunoglobulin levels in CAP patients may also uncover underlying humoral immunodeficiency or immuno-proliferative disorders