Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study.

Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B cell malignancies have profound and prolonged immunodeficiencies and are at risk for serious infections, including respiratory virus infections. Vaccination may be important for infection prevention, but there are limited data on vaccine immunogenicity in this population. We conducted a prospective observational study of the humoral immunogenicity of commercially available 2019-2020 inactivated influenza vaccines in adults immediately prior to or while in durable remission after CD19-, CD20-, or B cell maturation antigen-targeted CAR-T-cell therapy, as well as controls. We tested for antibodies to all four vaccine strains using neutralization and hemagglutination inhibition (HAI) assays. Antibody responses were defined as at least fourfold titer increases from baseline. Seroprotection was defined as a HAI titer ≥40. Enrolled CAR-T-cell recipients were vaccinated 14-29 days prior to (n=5) or 13-57 months following therapy (n=13), and the majority had hypogammaglobulinemia and cellular immunodeficiencies prevaccination. Eight non-immunocompromised adults served as controls. Antibody responses to ≥1 vaccine strain occurred in 2 (40%) individuals before CAR-T-cell therapy and in 4 (31%) individuals vaccinated after CAR-T-cell therapy. An additional 1 (20%) and 6 (46%) individuals had at least twofold increases, respectively. One individual vaccinated prior to CAR-T-cell therapy maintained a response for >3 months following therapy. Across all tested vaccine strains, seroprotection was less frequent in CAR-T-cell recipients than in controls. There was evidence of immunogenicity even among individuals with low immunoglobulin, CD19+ B cell, and CD4+ T-cell counts. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B cell aplasia. However, relatively impaired humoral vaccine immunogenicity indicates the need for additional infection-prevention strategies. Larger studies are needed to refine our understanding of potential correlates of vaccine immunogenicity, and durability of immune responses, in CAR-T-cell therapy recipients.

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.

Clinical and Virologic Characteristics and Outcomes of Coronavirus Disease 2019 at a Cancer Center.

BACKGROUND: High morbidity and mortality have been observed in patients with cancer and coronavirus disease 2019 (COVID-19); however, there are limited data on antimicrobial use, coinfections, and viral shedding. METHODS: We conducted a retrospective cohort study of adult patients at the Seattle Cancer Care Alliance diagnosed with COVID-19 between February 28, 2020 and June 15, 2020 to characterize antimicrobial use, coinfections, viral shedding, and outcomes within 30 days after diagnosis. Cycle threshold values were used as a proxy for viral load. We determined viral clearance, defined as 2 consecutive negative results using severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction results through July 30, 2020. RESULTS: Seventy-one patients were included with a median age of 61 years; 59% had a solid tumor. Only 3 patients had documented respiratory bacterial coinfection. Empiric antibiotics for pneumonia were prescribed more frequently early in the study period (February 29-March 28, 2020; 12/34) compared to the later period (March 29-June 15, 2020; 2/36) (P = .002). The median number of days from symptom onset to viral clearance was 37 days with viral load rapidly declining in the first 7-10 days after symptom onset. Within 30 days of diagnosis, 29 (41%) patients were hospitalized and 12 (17%) died. Each additional comorbidity was associated with 45% lower odds of days alive and out of hospital in the month following diagnosis in adjusted models. CONCLUSIONS: Patients at a cancer center, particularly those with multiple comorbidities, are at increased risk of poor outcomes from COVID-19. Prolonged viral shedding is frequently observed among cancer patients, and its implications on transmission and treatment strategies warrant further study.

Assessment of the Inclusion of Racial/Ethnic Minority, Female, and Older Individuals in Vaccine Clinical Trials.

Importance: Medical research has not equitably included members of racial/ethnic minority groups or female and older individuals. There are limited data on participant demographic characteristics in vaccine trials despite the importance of these data to current trials aimed at preventing coronavirus disease 2019. Objective: To investigate whether racial/ethnic minority groups and female and older adults are underrepresented among participants in vaccine clinical trials. Design, Setting, and Participants: This cross-sectional study examined data from completed US-based vaccine trials registered on ClinicalTrials.gov from July 1, 2011, through June 30, 2020. The terms vaccine, vaccination, immunization, and inoculation were used to identify trials. Only those addressing vaccine immunogenicity or efficacy of preventative vaccines were included. Main Outcomes and Measures: The numbers and percentages of racial/ethnic minority, female, and older individuals compared with US census data from 2011 and 2018. Secondary outcome measures were inclusion by trial phase and year of completion. Results: A total of 230 US-based trials with 219 555 participants were included in the study. Most trials were randomized (180 [78.3%]), included viral vaccinations (159 [69.1%]), and represented all trial phases. Every trial reported age and sex; 134 (58.3%) reported race and 79 (34.3%) reported ethnicity. Overall, among adult study participants, White individuals were overrepresented (77.9%; 95% CI, 77.4%-78.4%), and Black or African American individuals (10.6%; 95% CI, 10.2%-11.0%) and American Indian or Alaska Native individuals (0.4%; 95% CI, 0.3%-0.5%) were underrepresented compared with US census data; enrollment of Asian individuals was similar (5.7%; 95% CI, 5.5%-6.0%). Enrollment of Hispanic or Latino individuals (11.6%; 95% CI, 11.1%-12.0%) was also low even among the limited number of adult trials reporting ethnicity. Adult trials were composed of more female participants (75 325 [56.0%]), but among those reporting age as a percentage, enrollment of participants who were aged 65 years or older was low (12.1%; 95% CI, 12.0%-12.3%). Black or African American participants (10.1%; 95% CI, 9.7%-10.6%) and Hispanic or Latino participants (22.5%; 95% CI, 21.6%-23.4%) were also underrepresented in pediatric trials. Among trials reporting race/ethnicity, 65 (48.5%) did not include American Indian or Alaska Native participants and 81 (60.4%) did not include Hawaiian or Pacific Islander participants. Conclusions and Relevance: This cross-sectional study found that among US-based vaccine clinical trials, members of racial/ethnic minority groups and older adults were underrepresented, whereas female adults were overrepresented. These findings suggest that diversity enrollment targets should be included for all vaccine trials targeting epidemiologically important infections.

Antibiotic Prescribing and Respiratory Viral Testing for Acute Upper Respiratory Infections Among Adult Patients at an Ambulatory Cancer Center.

BACKGROUND: Outpatient antibiotic prescribing for acute upper respiratory infections (URIs) is a high-priority target for antimicrobial stewardship that has not been described for cancer patients. METHODS: We conducted a retrospective cohort study of adult patients at an ambulatory cancer center with URI diagnoses from 1 October 2015 to 30 September 2016. We obtained antimicrobial prescribing, respiratory viral testing, and other clinical data at first encounter for the URI through day 14. We used generalized estimating equations to test associations of baseline factors with antibiotic prescribing. RESULTS: Of 341 charts reviewed, 251 (74%) patients were eligible for analysis. Nearly one-third (32%) of patients were prescribed antibiotics for URIs. Respiratory viruses were detected among 85 (75%) of 113 patients tested. Antibiotic prescribing (P = .001) and viral testing (P < .001) varied by clinical service. Sputum production or chest congestion was associated with higher risk of antibiotic prescribing (relative risk [RR], 2.3; 95% confidence interval [CI], 1.4-3.8; P < .001). Viral testing on day 0 was associated with lower risk of antibiotic prescribing (RR, 0.4; 95% CI 0.2-0.8; P = .01), though collinearity between viral testing and clinical service limited our ability to separate these effects on prescribing. CONCLUSIONS: Nearly one-third of hematology-oncology outpatients were prescribed antibiotics for URIs, despite viral etiologies identified among 75% of those tested. Antibiotic prescribing was significantly lower among patients who received an initial respiratory viral test. The role of viral testing in antibiotic prescribing for URIs in outpatient oncology settings merits further study.