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)

ATTITUDES AND PREDICTORS OF COVID-19 VACCINE UPTAKE IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE

Background: Vaccination has proven to be an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine “hesitancy” has limited uptake in some populations. We surveyed individuals with inflammatory bowel disease (IBD) to explore factors associated with vaccine uptake, concerns, and which sources of information were considered trustworthy surrounding vaccination. Methods: Patients with IBD were recruited from a specialist IBD clinic at a tertiary hospital in Australia, and through a national IBD patient society (Crohn's & Colitis Australia). Patients were invited to complete an anonymous electronicsurvey between 31 October – 17 November 2021. Logistic regression was used to identify variables associated with vaccine uptake, using SPSS (Version 13.0 IBM). Results: There were a total of 441 respondents. Demographic and IBD characteristics are presented in Table 1. There were 337 females and 98 males. 262 (59.4%) had Crohns disease, 161 (36.5%) ulcerative colitis, and 18 (4.1%) indeterminant colitis. Most respondents 411 (93.2%) had received at least 1 dose of COVID-19 vaccination. 283 (61.9%) obtained BNT162b2 Pfizer, 133 (30.2%) ChAdOx1 nCoV-1 Astra Zeneca, and 5 (1.1%) mRNA-1273 Moderna. Most agreed that that vaccination in general was safe 306 (90.1%). Among 30 (6.8%) respondents who had not been vaccinated, concern about experiencing an IBD flare with vaccination and vaccine safety were most commonly identified. Multivariate analysis (Table 2) demonstrated past influenza vaccination (OR 3.28, 95% CI 1.34-8.9, p = 0.009) and self-perceived risk of being more unwell with COVID-19 infection due to IBD was positively associated with COVID-19 vaccine uptake (OR 5.25, 95% CI 1.96-14.04, p <0.001). The perceived risk of COVID-19 vaccination causing an IBD flare, and concern that vaccination is unsafe in pregnancy were both negatively associated with vaccine uptake (OR 0.28, 95% CI 0.10-0.77, p = 0.01) and (OR 0.22, 95% CI 0.08-0.65, p = 0.006) respectively. . Trust in healthcare workers was high with 282 (73.7%) responders ranking them the most trusted source to obtain information surrounding vaccination. Social media was ranked the least trusted source of information by 225 (58.6%). Conclusion: Past influenza vaccination and self-perceived risk of being more unwell with COVID-19 due to IBD, were positive predictors of COVID-19 vaccine uptake in IBD patients. Concerns about an IBD flare with vaccination is a unique consideration in those vaccine hesitant and is a negative predictor of vaccine uptake. Healthcare providers were ranked the most trusted source of information, highlighting the key role they have in exploring vaccination concerns and misconceptions in IBD patients. This is particularly so when navigating rapidly changing vaccine recommendations, and in the consideration of primary third dose and booster vaccination uptake. (Table Presented) (Table Presented)

HOSPITILISATIONS FOR NOROVIRUS DECREASE DURING THE COVID-19 PANDEMIC

Background Gastrointestinal infections cause a significant burden to the Australian healthcare system each year, with acute gastroenteritis infections costing up to $359 million AUD ($258 million USD) in 2016. Viral causes of gastroenteritis, particularly Norovirus, account for the majority of these cases. Given the contagious nature of many causes of bacterial and viral gastroenteritis, it was hypothesized that widespread lockdowns and increased public health focus on regular hand hygiene would contribute to a reduction in hospital presentations with gastrointestinal infections. Melbourne, Victoria, Australia first went into lockdown in March 2020 and remained in various forms of lockdown until late 2020. Methods A retrospective study comparing rates of hospitalization for bacterial and viral gastroenteritis was performed at The Royal Melbourne Hospital between February-August in both 2019 and 2020. Rates of admission were compared between the two years, as well as the causative organism and the outcome of the presentation. Descriptive statistics were provided to summarise demographic characteristics. Outcomes between the two years were compared using paired t-tests for continuous variables and Pearson chi-square for categorical variables. All data analysis was performed using Stata 16.1 and p-values £0.05 were considered statistically significant. Results Demographic data are summarised in Table 1. 283 patients were hospitalized with gastroenteritis in 2019 pre-pandemic, compared to 147 in 2020 during the COVID-19 pandemic. There was a significant reduction in the number of patients admitted with positive fecal cultures from 2019 to 2020 (87 vs 57, p < 0.01). The number and percentage of patients presenting with Norovirus reduced by greater than 90% in 2020 compared to 2019 (Table 2) (Odds Ratio: 0.093 [Confidence Interval: 0.02-0.41], p<0.01). There was a reduction in the number of presentations with Salmonella, however, this did not reach statistical significance (p=0.50). The number of patients presenting with Clostridium difficile significantly increased in 2020 compared to 2019 (21 versus 25, p=0.01) (Table 2). Rates of antibiotic treatment and intensive care admission were greater in 2020 compared to 2019 however there was no significant difference in biomarkers, length of stay, or mortality (Table 2). Conclusion A significant decrease in the incidence of hospitalization secondary to acute gastrointestinal infections was observed during the COVID-19 pandemic. Norovirus presentations decreased by greater than 90% between 2019 and 2020. The rate of other GI infections was similar between pre-pandemic and pandemic time points. These findings suggest that public health measures, such as social distancing and hand hygiene, may be a useful adjunct to prevent Norovirus infections in the future and could result in significant healthcare savings.(Table Presented)TABLE 1: PATIENT DEMOGRAPHICS(Table Presented) TABLE 2: GASTROINTESTINAL CULTURE POSITIVE INFECTIONS 2019 VERSUS 2020

Attitudes and predictors of COVID-19 vaccine uptake in patients with Inflammatory Bowel Disease

Background: Vaccination has proven to be an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine hesitancy has limited uptake in some populations. We surveyed individuals with IBD to explore factors associated with vaccine uptake, concerns, and which sources of information were considered trustworthy surrounding vaccination. Methods: Patients with IBD were recruited from a specialist IBD clinic at a tertiary hospital in Australia, and through a national IBD patient society (Crohn's & Colitis Australia). Patients were invited to complete an anonymous survey between 31 October - 17 November 2021. Logistic regression was used to identify variables associated with vaccine uptake. Data was analysed using SPSS (Chicago, IL). Results: There were a total of 441 respondents. Demographic and IBD characteristics are presented in Table 1. Most respondents 411 (93.2%) had received at least 1 dose of COVID-19 vaccination. Among 30 (6.8%) respondents who had not been vaccinated, concern about experiencing an IBD flare with vaccination and vaccine safety were most commonly identified. Of those who had not yet been vaccinated, the possibility of getting vaccinated in the future was likely in 3 (10.7%), unlikely in 12 (42.8%), whilst 13 (45.4%) were unsure about future vaccination. Multivariate analysis [Table 2] demonstrated past influenza vaccination (OR 3.28, 95% CI 1.34-8.9, p = 0.009) and self-perceived risk of being more unwell with COVID-19 infection due to IBD was positively associated with COVID-19 vaccine uptake (OR 5.25, 95% CI 1.96-14.04, p <0.001). Most agreed that that vaccination in general was safe 306 (90.1%). The perceived risk of COVID-19 vaccination causing an IBD flare, and concern that vaccination is unsafe in pregnancy were both negatively associated with vaccine uptake (OR 0.28, 95% CI 0.10-0.77, p = 0.01 and OR 0.22, 95% CI 0.08-0.65, p = 0.006) respectively. Trust in healthcare workers was high with 282 (73.7%) responders ranking them the most trusted source to obtain information surrounding vaccination [Figure 1]. Social media was ranked the least trusted source of information by 225 (58.6%). Conclusion: Past influenza vaccination and self-perceived risk of being more unwell with COVID-19 due to IBD, were positive predictors of COVID-19 vaccine uptake in IBD patients. Concerns about an IBD flare with vaccination is a unique consideration in those vaccine hesitant and is a negative predictor of vaccine uptake. Among those not yet vaccinated, 45% were uncertain about future vaccination. Given healthcare providers were ranked the most trusted source surrounding this domain, this survey highlights the key role they have in exploring vaccination concerns and misconceptions in IBD patients.

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.

Novel, low-volume, point-of-care coagulation test successfully detects anticoagulation resistance in hospitalized patients with COVID-19

Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19.Hypothesis: Evaluation of a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE. Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (<10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response. Results: The CTS detected subtherapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R =0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 94% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%). Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.

Christmas article: The effect of correct use of face masks in preventing disease transmission in a standardised study population

INTRODUCTION: Through centuries, face masks have been used by health professionals to prevent disease transmission. Currently, there is an increased use of face masks due to the corona pandemic. However, the preventive effect of face masks is still unclear. The aim of this study is to investigate the effect of correct use of face masks, without touching the face, in the prevention of disease transmission in a standardised study population. METHODS: We used a standardised study population consisting of Danish cakes "kajkager". One kajkage was wearing a face mask and one kajkage did not wear a face mask, n=2. Kajkager consist of approximately 100% sugar. Since kajkager have no arms, correct use of the face mask was guaranteed. The study population was placed in a hospital setting and observed for six months regarding weight, surface and filling. Changes in these parameters were used as a surrogate measure of disease transmission. RESULTS: After the six months observation period, both study groups had a similar decline in weight. We observed no significant differences on the surface, but the kajkage wearing a facemask had a slightly fresher filling. CONCLUSION: Correct use of face masks has no significant effect on weight, surface or filling in kajkager and therefore no effect on disease transmission in this study population. Thus, in December when the Danish population consumes very large quantities of sugar, health personnel may omit using face masks without an increased risk of disease transmission.none.