PurposeBlood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group.MethodsLung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves.ResultsA total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility.ConclusionTransplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities. Blood group O individuals are universal donors, but O recipients are limited to O donors. This constraint combined with the current lung allocation system places O recipients at a hypothetical disadvantage. This study evaluates waitlist outcomes, post-transplant outcomes, and overall survival from time of listing by blood group. Lung transplant candidates from 2/2015 - 2/2019 were identified from the Scientific Registry of Transplant Recipients. A Fine and Gray model adjusted for OPO region, height, sex, and LAS was used to determine the competing risk for waitlist mortality or transplant by blood group and a model adjusted for LAS at transplant used to determine the competing risk for post-transplant mortality. A Cox proportional hazards regression model utilizing a time-varying covariate of transplant and adjusted for the above was used to determine the adjusted risk from listing to death by blood group. Unadjusted outcomes were visualized using Kaplan-Meir curves. A total of 9,846 candidates were identified, with 8,181 (83%) receiving a lung transplant and 964 (10%) experiencing waitlist death. Blood group A candidates had higher adjusted access to transplant (sHR 1.23, 1.17-1.29) and lower waitlist mortality (sHR 0.77, CI 0.66-0.89) (Fig 1a). AB candidates had a higher adjusted access to transplant (sHR 1.24, CI 1.1-1.4). There was no difference in the adjusted risk for post-transplant death by blood type (Fig 1b). There was no significant difference in mortality from time of listing across blood groups (Fig 1c) and in graft failure or post-transplant mortality by ABO compatibility. Transplant equity varies across blood groups with significant differences in adjusted access to transplant and waitlist mortality by blood group. Despite this, post-transplant survival and survival from the time of listing are similar across blood groups. These results support the need to reconsider allocation schemas to mitigate blood group waitlist inequalities.

AbstractBackgroundFavipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.MethodsWe conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1:1 to receive placebo or favipiravir (1800 mg BID Day 1, 800mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 deep sequencing, we assessed favipiravir’s impact on mutagenesis.ResultsFrom July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants’ mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48 – 1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54 – 1.29; sustained: HR 0.87, 95% CI 0.52 – 1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.ConclusionsOur data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.Trial registration numberNCT04346628SummaryIn this phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or uncomplicated patients with COVID-19, we found no difference in time to shedding cessation or time to symptom resolution by treatment arm.

Oral immunotherapy (OIT) desensitization is an emerging treatment for food allergy. Despite attempts to minimize adverse events during desensitization, many participants still experience gastrointestinal symptoms and some develop eosinophilic esophagitis (EoE). It is unclear whether these subjects have subclinical esophageal eosinophilia (EE) at baseline. We evaluated the presence of EE in subjects with food allergy before peanut OIT. Baseline esophagogastroduodenoscopies (EGD) were conducted with 21 adults before peanut OIT. Endoscopic findings were assessed using the EoE Endoscopic Reference Score (EREFS), and biopsies were obtained from the proximal, middle, and distal esophagus. Esophageal biopsies were evaluated using the EoE Histologic Scoring System (EoEHSS). Hematoxylin and eosin stains of each biopsy were assessed for eosinophil density. Automated image analysis of eosinophil peroxidase (EPX) immunohistochemistry was also performed to assess eosinophil degranulation. All subjects were asymptomatic at enrollment. Pre-existing EE was present in 5 participants (24%), 3 (14%) of whom had >15 eosinophils per high-power field (eos/hpf) associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS=0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis of the esophageal mucosa. EPX deposition (EPX/mm2) correlated with eos/hpf (r=0.53, p<0.0001) EE is present in some (24% in this study) adults with IgE-mediated peanut allergy before initiation of OIT. Such eosinophilic inflammation may be accompanied by mild endoscopic and histologic findings. Additional EGD and biopsies for longitudinal data collection during OIT are ongoing and may provide insight into mechanisms underlying gastrointestinal side effects.

Omalizumab has shown efficacy as an adjuvant to multi-food oral immunotherapy (mOIT). However, there is no evidence of the minimum dose necessary for optimal outcome.

Introduction Oral food challenges (OFCs) are considered the gold standard of diagnosing food allergy. Repeat food challenges are necessary to assess if food allergies are persistent or outgrown. Methods A retrospective chart review was conducted on all clinical protocols initiated at our institution involving standardized screening OFCs. Analysis was performed among participants who were challenged to the same food twice at variable time points. Repeat challenges were available for 8 food allergens. Allergic reactions were assessed by modified Bock's criteria and ranked in order of severity. Results Twenty-eight participants repeated challenges to the same allergen once or twice for a total of 65 challenges. Forty-two positive challenges corresponding to 18 participants were analyzed. Peanut had the largest number of repeat challenges (n=19 participants), followed by almond (n=4), milk, walnut and egg (n=2), cashew, hazelnut, and sesame (n=1). Among the positive challenges, sixteen repeat challenges were conducted to peanut, two to egg, and one each to almond, milk, and walnut. In participants with a repeat positive food challenge, the eliciting dose (ED) did not change (p=0.66), but reactions were more severe (p=0.02). Change in either ED or severity rank was not associated with time between repeat challenges (p=0.94 and p = 0.56, respectively). Additionally, our analysis showed that symptoms varied widely during subsequent challenges. Conclusions Our findings show increased severity with variable allergic reactions between OFCs, regardless of the duration of time between challenges. Larger cohorts are needed to validate these preliminary findings.

Introduction Improved biomarkers predictive of food challenge thresholds are needed. Methods A retrospective chart review was performed on IRB-approved clinical protocols where standardized screening oral food challenges (OFCs) to a cumulative dose of 500 mg protein were conducted to any of 11 potential food allergens. Dose-dependent receiver operating characteristic (ROC) curves for specific IgE (sIgE), sIgE/total IgE ratio (sIgEr), and skin prick test (SPT) were generated to determine optimal allergen-specific biomarker thresholds predictive of OFC outcome adjusting for cumulative tolerated dose (CTD). Results A total of 1274 OFCs completed by 427 participants were analyzed. The majority of food-specific SPT, sIgE, and sIgEr thresholds calculated from the CTD-dependent ROC curves were highly predictive of OFC outcome [area under the curves (AUCs) > 0.75]. Participants with values above the thresholds were more likely to have a positive challenge and react at lower doses compared to those with values below (p Conclusions These reported SPT, sIgE, and sIgEr threshold values appear highly predictive of challenge outcome and may serve as a substitute for food challenges in the appropriate setting.

Double-blind, placebo-controlled, food challenges (DBPCFCs) are considered the gold standard for diagnosing food allergy. Previous literature suggests an increased rate of anaphylaxis in adults and adolescents compared to children based on emergency room presentations, which may raise concern when considering an oral food challenge. There is limited data comparing adverse events (AEs) across different age groups during oral food challenges in food allergic individuals.