ABSTRACT
Background: Among immunocompromised patients with immune mediated infammatory diseases (IMIDs), those undergoing therapy with B cell depleting agents are among the most vulnerable to both severe COVID-19 disease and sub-optimal response to COVID-19 vaccines(1). Numerous studies have documented suppressed humoral, but relatively maintained cell mediated, responses to COVID-19 vaccines in these patients. However, the clinical signifcance of such immunity in terms of protection from infection and its sequelae are poorly understood. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Objectives: To defne the frequency and outcomes of COVID-19 breakthrough infection in fully or partially vaccinated IMIDs patients receiving B cell depleting therapies. To assess the characteristics and risk factors for severe outcomes and death. Methods: All pharmacy records from within a large health care system were electronically searched for patients undergoing B cell depleting therapies with approved monoclonal antibodies in 2020. Records with ICD codes for IMIDs but not malignancies were included;patients must also have had at least one documented COVID-19 vaccine. From this cohort all patients with breakthrough COVID-19 disease from time of 1st vaccination through December 15, 2021 were identifed;each record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, use of monoclonal antibodies, dose and timing of B cell depleting therapy, and outcomes as assessed by an 8 point NIH ordinal scale. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results: A total of 1677 IMIDs patients were identifed who received any B cell depleting monoclonal antibody and at least one COVID-19 vaccine in 2021. From this cohort 74 patients (4.4%) experienced a breakthrough COVID-19 infection. Among the breakthrough patients 34 (46%) had a rheumatic disease (RA 11, AAV 15, SLE 2), 34 (46%) had CNS infammatory disease (MS 32, 2 other), and 6 (8%) had immune hematologic/miscellaneous diseases. Four patients had a previous history of COVID-19 infection. Overall 24 (35%) were hospitalized with 11 patients requiring critical level care (15%) and 6 deaths (8 %). All fatal cases had rheumatic diseases. Monoclonal antibodies were given as outpatient therapy to 21 patients and among these only 1 patient was hospitalized without requiring O2 and none died. In univariate analysis only number of comorbidi-ties had a signifcant positive effect (p=.001) on severe outcomes (i.e. groups 1-4 vs. groups 5-8: Table 1) while monoclonal antibody therapy was associated with more favorable outcomes (p=.005 group 1-2 vs.3-8, Table 1). There were no associations between the dose, duration or timing of the B cell therapy, concomitant therapies including glucocorticoids, vaccine status (incomplete, complete, boosted) or date of vaccination with severe outcomes. Conclusion: In IMIDs patients treated with B cell depleting therapies breakthrough infections are common with many experiencing severe outcomes. Concomitant comorbidities were associated with risk of severe disease. Monoclonal antibody therapy was used in only 28% but was associated with enhanced clinical outcomes with only 1 in 21 requiring hospitalization and zero mortality. This population of immunocompromised patients remains vulnerable to COVID-19 disease despite vaccination. More aggressive use of outpatient management with monoclonal antibody therapy and other preventive and therapeutic measures are urgently needed.
ABSTRACT
Introduction: The Covid-19 pandemic in the UK led to much un-certainty about the delivery of cancer services. A shift from established therapy (and its timing) in patients with Muscle invasive Bladder Cancer (MIBC) has potential deleterious consequences. To understand outcomes, we formed a collaborative to measure overall and diseasefree survival at 3-years in patients with non-metastatic MIBC (Figure 1) treated during the UK's first wave of Covid-19. Secondary aims included comparison between treatment modalities and pre-Covid controls. Patients and Methods: The collaborative included clinicians from 13 major centres, representing 3 UK nations. A prospective clinical audit, endorsed by the National Cancer Research Institute, was started to collect comprehensive data. MIBC patients discussed at the multidisciplinary meeting (MDM) between 1/3/2020-30/06/2020 were included. Results: At submission, data were available from 12 centres for 299 patients. The mean age was 69.3 years (27- 90), and there were 72 female and 227 male patients. Mean Charlson Co-morbidity Index was 5 (1-12). Preliminary analysis of available data indicate the following: MDM recommendations for (at least) 1 in 4 patients were deemed as being modified from standard practice. Twenty six patients received neoadjuvant chemotherapy. In total (from available data), 99 received radical radiotherapy and 146 underwent radical cystectomy (65 and 74 specified as open and robotic assisted, respectively). Preliminary analysis suggests that 1 in 3 patients had died within 1 year. Conclusions: Preliminary Results indicate that recommendations for MIBC patients were significantly altered consequent to the pandemic and mortality was high. Analyses towards endpoints are awaited.
ABSTRACT
Background: Over the previous 48 months the training landscape has been significantly disrupted as a result of the COVID-19 pandemic. This has compounded pre-existing challenges for trainees relating to training requirements, exams, service demands, and other personal circumstances. As a result, the need for advocacy and representation of trainees within the RANZCP has never been greater. However, opportunities for trainees to directly engage in College dialogue and decision-making remains limited. These limitations are out of keeping with contemporary processes for trainee representation across other specialty Colleges in Australasia. To progress these discussions further, we believe that trainees need to first have a seat at the table. Objectives: •• Deliver a trainee-led discussion with a focus on the RANZCP training pathway and associated trainee experiences;•• Describe the challenges faced by RANZCP trainees during the COVID-19 pandemic;•• Describe the challenges reasonably expected in a post-COVID-19 training landscape;•• Explore the role of trainee representation within the RANZCP. Methods: This session will utilise the representation of a diverse group of trainees, recognising that representation within the RANZCP currently takes many forms. The panel will consist of representatives from state-based Associations of Trainees (APTs), current and resigning members of the RANZCP Trainee Representative Committee (TRC), and individual trainee members. Conclusions: Trainees have been impacted by the COVID-19 pandemic and subsequent disruptions to training and assessment. Although trainees are the future of the RANZCP, opportunities for trainees to engage in College dialogue and decision-making remains limited. Further engagement of trainee representation within the RANZCP is needed. It's time for trainees to have a seat at the table.
ABSTRACT
Introduction: Several studies have demonstrated reduced serological response to SARS-CoV-2 vaccines in multiple sclerosis (MS) patients treated with anti-CD20 and sphingosine 1-phosphate receptor (S1PR) modulator disease modifying therapies (DMTs). However, there are limited data on the factors affecting protective immunity. Objectives: Investigating factors affecting protective immunity in a population of patients with MS Methods: MS Patients on DMT diagnosed with COVID-19 following at least one dose of a SARS-CoV-2 vaccine were identified in the Cleveland Clinic COVID-19 registry or during routine clinical care. Cases outside the registry were confirmed to have positive SARS-CoV-2 by PCR at time of diagnosis. Demographics, disease history, DMTs, comorbidities, exposures, vaccination status, and COVID-19 outcomes were collected from the registry or chart review. Additional data collection is ongoing for patients vaccinated outside the Cleveland Clinic. Results: 18 patients were identified (13 relapsing remitting, 2 secondary progressive, and 2 primary progressive MS): 13(72.2%) female, 14(77.8%) Caucasian, median age 43 years, median disease duration 12.5 years. Of the 10 patients for whom detailed vaccination data are readily available, 80% completed a full vaccination series. All received an mRNA vaccine. In the registry population, 8/629 (1.3%) fully vaccinated and 2/130 (1.5%) partially vaccinated patients tested positive for COVID- 19 after vaccination. 11(61.1%) were on anti-CD20 therapies, 5(27.1%) S1PR modulators, and 2(11.1%) dimethyl fumarate. 4 patients were hospitalized. Median length of stay was 8, range 1-15. No patients required supplemental oxygen, intubation, or ICU stay. 1 patient was discharged to a rehabilitation hospital and 3 home Conclusions: Patients treated with anti-CD20 agents and S1PR modulators still may be at risk for COVID-19 despite vaccination. While still at risk for hospitalization, intubation and death from COVID-19 appear rare. Larger studies analyzing the temporal relation between DMT administration and vaccination, and the relationship of serological response and overall protective immunity are needed to guide patient counselling.