HUMORAL AND T CELL RESPONSES TO COVID-19 VACCINATION IN INFLAMMATORY BOWEL DISEASE

BACKGROUND: The characteristics of SARS-CoV-2 vaccine-induced immunity in inflammatory bowel disease (IBD) patients on immune modifying agents has not been clearly defined due to their exclusion in vaccine trials. Emerging results suggest infliximab impairs antibody response compared to vedolizumab. However there has not been direct comparison to controls. We evaluated this with both humoral and T cell response in IBD patients. METHODS: Antibody and T cell response were analysed in IBD patients who received BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccination from a single Australian centre. The control group were healthcare workers (HCW) without IBD. Blood samples were taken at 4 time points: at baseline V0 (before vaccination);V1 (7- 14 days after vaccine 1);V2 (7-14 days after vaccine 2);V3 (21-42 days after vaccine 2). Antibodies to the S1/2 IgG subunit and receptor-binding protein (RBD) were measured and reported here. RESULTS: 88 (28 ulcerative colitis, 50 Crohn's disease) IBD patients were included and compared to 53 healthy controls (Table 1). IBD patients medications included 6 5ASA (6.8%), 6 immunomodulator monotherapy (6.8%), 14 anti-TNF monotherapy (15.9%), 32 anti-TNF combination therapy with immunomodulator (36%), 16 IL12/23 (18%) and 13 vedolizumab (14%). Pre-vaccine baseline sera showed absence of anti-RBD antibodies in all participants. 84 patients (87%) received BNT162b2 and 4 (4.5%) received ChAdOx1 nCoV-19 vaccines. Geometric mean [SD] anti-S1/2 antibody concentrations at 4 weeks after second vaccination (V3) were significantly lower in IBD TNF treated patients (162.6[1.7]) compared to IBD non TNF treated patients (325.2[1.3]), and healthy controls (325.2[1.3]), p<0.0001 (Figure 1). There was no difference between non-TNF treated patients including those on vedolizumab or IL12/23 compared to controls. Similarly there was a significant difference between anti-RBD IgG titres between TNF and non-TNF IBD patients at V3 but not when compared to controls. There was no difference in RBD IgG and anti-S1/2 antibodies between anti-TNF monotherapy and combination therapy. All healthy controls and most IBD patients seroconverted at V3. 2 patients that failed to seroconvert were on steroid. CONCLUSION: TNF agents influence SARS-CoV-2 vaccine-induced antibody response in IBD patients, with lower anti-S1/2 IgG concentrations compared to non-TNF IBD patients and healthy controls. However, there was no difference in RBD IgG concentrations. It is unclear whether these subtle differences in antibody response in IBD patients on TNF agents is biologically meaningful, as most seroconverted after second dose vaccination. They may translate to differences in antibody longevity, but this is yet to be demonstrated. Neutralising antibody and T cell (CD4+/CD8+/follicular T cell) data from this study to come. (Table Presented) (Figure Presented)

Time Spent in the Electronic Health Record by Neurologists: Analyzing daily use inside and outside the clinic using EPIC Signal data

Objective: To quantify how long neurologists spend in the electronic health record (EHR). Background: Neurologists have extensive information needs for decision-making (e.g., neuroimaging, video-recordings) that are likely to affect time spent in the EHR. While EHRrelated burden is being increasingly studied due to the national spotlight on physician burnout, few studies have focused on neurology. Design/Methods: Data were obtained using Epic Signal, which provides detailed data on how long clinicians spent on different EHR interfaces. We focused on all neurologists from an academic health system in Florida who practiced during November 2019 to October 2020 inclusive. Our EHR outcome measures were time spent interacting with the EHR, time spent in the EHR outside scheduled clinic hours, inbox management, writing notes, and chart review. We reported the median and range of outcome measures because they had skewed distributions. We also assessed whether changes related to the coronavirus pandemic (e.g., telemedicine adoption) were associated with differences in EHR use via Wilcoxon signed-rank tests. Results: Our sample contained 2,286 physician-week observations (83 neurologists). They spent up to: 333.6 minutes/day (median:66.5, range:0.5-333.6) interacting with the EHR, 303.4 minutes/day (median:27.8, range:0.0-303.4) in the EHR outside scheduled hours, 45.6 minutes/day (median:3.4, range:0.0-45.6) in the In Basket, 240.3 minutes/day (median:31.1, range:0.0-240.3) writing notes, and 73.1 minutes/day (median:11.0, range:0.0-73.1) in clinical review. EHR measures were comparable before and during the pandemic. Conclusions: Similar to physicians in other specialties, neurologists spend a significant proportion of their clinical effort engaged with the EHR. Neurologists may benefit from interventions that reduce time spent in the EHR, such as after-hours EHR use and documentation.

Humoral and T cell responses to COVID-19 vaccination in IBD

Background: The characteristics of SARS-CoV-2 vaccine-induced immunity in inflammatory bowel disease (IBD) patients on immune modifying agents has not been clearly defined due to their exclusion in vaccine trials. Emerging results suggest infliximab impairs antibody response compared to vedolizumab. However there has not been direct comparison to controls. We evaluated this with both humoral and T cell response in IBD patients. Methods: Antibody and T cell response were analysed in IBD patients who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination from a single Australian centre. The control group were healthcare workers (HCW) without IBD. Blood samples were taken at 4 time points: at baseline V0 (before vaccination);V1 (7-14 days after vaccine 1);V2 (7-14 days after vaccine 2);V3 (21-42 days after vaccine 2). Antibodies to the S1/2 IgG subunit and receptor-binding protein (RBD) were measured and reported here. Results: 88 (28 ulcerative colitis, 50 Crohn's disease) IBD patients were included and compared to 53 healthy controls (Table 1). IBD patients medications included 6 5ASA (6.8%), 6 immunomodulator monotherapy (6.8%), 14 anti-TNF monotherapy (15.9%), 32 anti- TNF combination therapy with immunomodulator (36%), 16 IL12/23 (18%) and 13 vedolizumab (14%). Pre-vaccine baseline sera showed absence of anti-RBD antibodies in all participants. 84 patients (87%) received BNT162b2 and 4 (4.5%) received ChAdOx1 nCoV-19 vaccines. Geometric mean [SD] anti-S1/2 antibody concentrations at 4 weeks after second vaccination (V3) were significantly lower in IBD TNF treated patients (162.6[1.7]) compared to IBD non TNF treated patients (325.2[1.3]), and healthy controls (325.2[1.3]), p<0.0001 (Figure 1). There was no difference between non-TNF treated patients including those on vedolizumab or IL12/23 compared to controls. Similarly there was a significant difference between anti-RBD IgG titres between TNF and non-TNF IBD patients at V3 but not when compared to controls (Figure 2). There was no difference in RBD IgG and anti-S1/2 antibodies between anti-TNF monotherapy and combination anti-TNF with immunomodulator. All IBD and healthy controls seroconverted at V3 (Figure 3). Conclusion: TNF agents influence SARS-CoV-2 vaccine-induced antibody response in IBD patients, with lower anti-S1/2 IgG concentrations compared to non-TNF IBD patients and healthy controls. However, there was no difference in RBD IgG titres between controls and IBD patients overall. It is unclear whether these subtle differences in antibody response in IBD patients on TNF agents is biologically meaningful, as all groups seroconverted after second dose vaccination. Neutralising antibody and T cell data (CD4+/CD8+) from this study to come.

Prolonged positive SARS-CoV-2 RT-PCR in cancer outpatients requires specific reorganization of cancer centres

Background: Patients with cancer are more susceptible to infection because of immunosuppressive treatment given to cure cancer. Several guidelines published at the beginning of the COVID-19 pandemic recommend delaying systemic anticancer treatment until complete resolution of COVID-19 symptoms. In addition, it is important to segregate patients with cancer from patients with COVID-19 to avoid transmission. Nevertheless, some patients will present both diseases, and the duration of eviction from cancer units and delay of cancer treatment after COVID-19 remains unclear. Notably the duration of viral excretion after COVID-19 is a concern in immunosuppressed patients. Methods: We tested all patients with a confirmed initial diagnosis of COVID-19 who needed to receive cancer or immunosuppressive treatment for a solid tumour, haematological or inflammatory disease in our centre from April 1st to May 15th 2020. We have repeated SARS-COV2 RT-PCR until negative viral shedding. Results: We tested 49 consecutive patients: 53% had solid tumours, 37% haematological disease and 10% inflammatory disease. 59% were under 65 years. Overall, 82% of patients had a positive RT-PCR from day 14 to 20 after the initial diagnosis of COVID-19 infection, 60% from day 21 to 27 and 30% from day 28 to 34. Only 4/37 patients evaluated remained with a positive RT-PCR after day 35. No predictive factors were associated with a positive RT-PCR but our results suggest that patients treated for inflammatory disease had a shorter duration of positive RT-PCR. 18 patients had their treatment delayed according to guideline recommendations and 17 patients received their treatment in a dedicated COVID-19 outpatient unit. No symptomatic COVID-19 recurrence was observed during follow-up in patients who had received chemotherapy despite persistent positive RT-PCR. Conclusions: We report here the first assessment of SARS-CoV2 RT-PCR kinetic in cancer patients. A prolonged viral excretion is observed in patients treated for cancer. A systematic retest is needed after day 14 if RT-PCR remains positive. A specific unit dedicated to outpatients with persistent positive RT-PCR allows urgent anticancer treatment and avoids the risk of viral exposure for other immunodepressed patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.