ABSTRACT
Background: Patients with autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) have a frameshift mutation on one allele of the MUC1 genotype, resulting in production an abnormal MUC1frameshift protein on on allele and normal MUC1 on the other allele. The C variant of the rs4072037 SNP increases production of MUC1 or MUC1fs if it is contained in the corresponding promoter. In addition to the kidneys, MUC1 is expressed in the nose and lungs. ADTKD-UMOD has a very similar clinical presentation, but UMOD is expressed only in the kidney. Method(s): We conducted a survey (after emergence of the delta variant) using the REDCAP database of 957 individuals in our ADTKD cohort to determine if COVID-19 infection was more severe in ADTKD-MUC1 patients. Result(s): There were 89 ADTKD-MUC1 and 132 ADTKD-UMOD respondents, with similar age, body mass index, transplant rates, vaccination rates,. 25/89(28%) ADTKDMUC1 individuals developed COVID-19 vs. 21/132(16%) ADTKD-UMOD individuals (odds ratio 2.35(1.6-3.1) (p=0.028). 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) ADTKD-UMOD individuals (p=0.013), with an odds ratio of 9.4 (7.2-11.5). The mean plasma mucin1 level in 13 infected and 23 uninfected ADTKDMUC1 individuals was 6.40+/-3.4 vs.10.89+/-3.82 U/mL (p=0.0012). Of ADTKD-MUC1 individuals who developed COVID-19, only 19% had the CC phenotype (associated with increased MUC1 production) vs. 51% of the ADTKD-MUC1 individuals who did not develop COVID-19 (p=0.01). There was no difference in rs4073037 genotype frequencies in the ADTKD-UMOD group. Of the 10 ADTKD-MUC1 patients who died, 8 were transplanted, with only 3 greater than 60 years of age. 50 percent had received 2 COVID-19 vaccines. Conclusion(s): Patients with ADTKD-MUC1 have a 2-fold increased odds of developing COVID-19 and a 9-fold increased mortality from COVID-19. Among ADTKD-MUC1 patients, those producing less MUC1 were more likely to develop COVID-19.
ABSTRACT
Introduction: Clinicians in academia face four major career challenges: 1. Gaining clinical advice from colleagues experienced in a particular disease or treatment 2. Experiencing Life-long coaching and mentoring from senior experienced clinicians 3. Accessing high quality continuing medical education relevant for patient care 4. Support to carry out medical research All four challenges have been adversely impacted during the Covid-19 pandemic as traditional face-to-face networks have become harder to access. This is especially pertinent when treating complex or rare diseases like acute lymphoblastic leukemia (ALL). Atypical or refractory patients, and those who experience toxicities often benefit from timely input from experts with considerable experience managing ALL. Online networks offer a robust pandemic-proof source of health and care support and advice. Until recently there have been few dedicated professional networks that provide a regular online forum dedicated to research and care on specific diseases across countries and none related to ALL. Methods: We describe the Resonance ALL Research and Care Network (ALL RCaN;https://resonancehealth.org/networks/all-rcan ) which includes a network of colleagues and a weekly, multidisciplinary online forum that brings together pediatric and adult hematologists and oncologists from around the world to share data, discuss cases and support patient care. In addition, there is a monthly ‘Fellows Fourth Friday’ to help fellows build their own professional network and gain scientific and clinical advice. The network was born out of a monthly meeting of study chairs (the “Study Chair Affinity Group”) for ALL research protocols which had been running for 10 years. Results: The network launched formally in June 2020 with 30 founding members but has expanded rapidly through word of mouth. The Acute Leukemia network grew by 850% by Dec 2020 and 1460% by March 2021 and as of July 2021 has 579 members across 18 time zones. It has succeeded in 'Building ALL Bridges“ between physicians that treat adults and pediatricians for joint discussions in acute leukemia. This collaboration has been severely lacking in the past. The network also presents selected s from major national and international conferences every 4 weeks. This model has been replicated for other cancers including the Global Neuroblastoma Network (resonancehealth.org/networks/gnn) and High-dose Methotrexate Quality Improvement Network (resonancehealth.org/networks/hdmtx). Network software development, video conferencing, meeting coordination, and content hosting have been funded by volunteer network leaders, many volunteer presenters, philanthropic contributions, and unrestricted educational grants. Now that the Resonance infrastructure is fully developed (and available to all at no cost), most Networks function well without funding. Conclusions: Providing free video conferencing, content hosting, and network management tools combined with dedicated leadership and clinically relevant discussions and presentations has led to massive growth of the ALL Research and Care Network, which continues to grow. Networks for other cancers are in various stages of development since the tool set and methodology easily scales to new groups of colleagues and new diseases. [Formula presented] Disclosures: Guscott: EUSA Pharma UK Ltd: Ended employment in the past 24 months. Douer: Amgen: Consultancy, Speakers Bureau;Servier: Consultancy, Speakers Bureau;Jazz: Consultancy;Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau. Howard: Cellworks Group Inc.: Consultancy;Sanofi: Consultancy, Other: Speaker fees;Servier: Consultancy.