ABSTRACT
Conspiracy theorists' unpopular opinions likely make them more apprehensive about interactions with others, frustrating their need to belong. Therefore, they may be susceptible to believing misinformation because evidence that others share their beliefs provides "social proof” that they can expect interactions with others to be positive and rewarding. The present research examined whether alternatively fulfilling the need for social connection through romantic relationships could protect conspiracy theorists against COVID-19 misinformation. In a 3-week daily diary study (N = 555), experimental participants implicitly learned to associate their romantic partners with positive experiences (by repeatedly pairing their partner with highly positive and approachable stimuli, McNulty et al., 2017). We then assessed how much participants trusted individuals they might normally distrust, as a manipulation check, and how much participants tuned their daily personal beliefs and behavior to match the U.S. public's daily susceptibility to COVID-19 misinformation. Participants high on conspiratorial thinking trusted fellow community members more in the experimental than control condition. Participants high on conspiratorial thinking in the experimental condition were also less likely to treat the U.S. public's greater daily susceptibility to COVID-19 misinformation as proof that they could discount the virus. The present findings suggest that rewarding romantic connections might be leveraged to limit conspiracy theorists' susceptibility to believing public skepticism about COVID-19. © 2023 The Authors
ABSTRACT
People who believe they are invulnerable to infectious diseases often fail to protect themselves against the disease threats that others pose to them. The current paper hypothesizes that social pain-the experience of feeling interpersonally hurt or rejected-can sensitize the behavioral-immune system by giving people added reason to see others as worthy of protecting themselves against. We obtained four daily diary samples involving 2,794 participants who reported how hurt/rejected they felt by those they knew, how personally concerned they were about the spread of illness/COVID-19, and how vigilantly they engaged in self-protective behaviors to safeguard their health each day. An integrative data analysis revealed robust evidence that people who believed they were invulnerable to infectious disease engaged in more concerted efforts to protect themselves against the greater daily risk of contracting COVID-19 when being in acute social pain gave them added reason to see others as harmful to them.
ABSTRACT
Although the isolated threat of disease often motivates people to avoid others, people need the help and cooperation of others to protect themselves against pandemic disease threats. Therefore, the fear of contracting a highly contagious virus like COVID-19 should motivate people to believe that they can in fact count on the help and cooperation of others for protection. Trusting in others provides the basis to anticipate their cooperation. Therefore, we expected a greater daily threat of contracting COVID-19 to motivate people to trust more in others, providing needed assurance that others would keep them safe from harm. We obtained 4 daily diary samples involving 2794 participants who provided in excess of 18,000 daily observations within the first three months of the COVID-19 pandemic. Each day, we tracked (1) disease threat, captured daily by personal concerns about COVID-19 and infection totals in the nearest most populous city, and (2) trust in others, captured daily by expressions of trust in intimates, collective caregivers (e.g., President, Congress), and strangers. Participants in two samples completed 2-month follow-ups. Integrative analyses of the daily diaries revealed that people trusted more in intimates and collective caregivers on days they had greater (vs. less) reason to be concerned about COVID-19. Further integrative analyses of the follow-up data revealed that participants who were initially more likely to trust in others on days when COVID-19 cases in nearby communities spread more rapidly later reported greater confidence that others would keep them safe from harm. That is, they evidenced greater physical, interpersonal, and collective security in social connection than participants who were initially less likely to defensively trust in others on such occasions. The present findings suggest that ecological threats may dynamically motivate people to trust others more than they otherwise would, providing optimism that collectively-faced crises may motivate social cooperation when it is most needed. © 2022
ABSTRACT
Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .
ABSTRACT
Background. Increased prescribing of antibiotics commonly used for respiratory infections, including azithromycin, ceftriaxone, and doxycycline was observed in nursing homes (NH) during the COVID-19 pandemic however antibiotic prescribing was not linked to resident diagnosis. Therefore, our objective was to characterize antibiotic prescribing in residents with SARS-CoV-2 infection in a large cohort of US NHs. Methods. We conducted a retrospective cohort study using PointClickCare (PCC) data containing longitudinal NH electronic health records. We included 4,891 NHs that reported >=1 medication order/month from April 2020-November 2021. We identified the first onset of SARS-CoV-2 infection using ICD-10-CM diagnosis code U07.1. To validate the number of SARS-CoV-2 infections per facility captured in PCC, we compared the total number of SARS-CoV-2 infections documented in PCC to those reported to the National Healthcare Safety Network (NHSN). Antibiotic orders were determined to be associated with a SARS-CoV-2 infection if 3 days before or <=7 days after diagnosis. We characterized the proportion of residents with a SARS-CoV-2 infection with an associated antibiotic by month. Results. We included 2,086 (43%) NHs that had <=20% difference in total number of SARS-CoV-2 infections documented in PCC and reported to NHSN. From April 2020-November 2021, a total of 118,180 residents with a SARS-CoV-2 infection were identified and 24% had an associated antibiotic prescription (N=27,972). The highest prescription rate (30%, 95% Confidence Interval [29%-31%]) was observed in April 2020 and varied by less than 8% from May 2020-November 2021 (Fig.1). The most commonly prescribed antibiotics were azithromycin (53%), doxycycline (13%) and ceftriaxone (10%). Conclusion. An antibiotic prescription was linked to up to a quarter of NH residents with SARS-CoV-2 infection, highlighting potential opportunities for avoiding unnecessary antibiotic prescribing for viral infections in NHs. Appropriate antibiotic prescribing in NH populations is important to reduce potential harm when antibiotics offer no treatment benefit to the resident. Identifying facility-level characteristics that lead to variability in antibiotic prescribing is a next step to inform antibiotic stewardship interventions.
ABSTRACT
People who believe they are invulnerable to infectious diseases often fail to protect themselves against the disease threats that others pose to them. The current paper hypothesizes that social pain—the experience of feeling interpersonally hurt or rejected—can sensitize the behavioral-immune system by giving people added reason to see others as worthy of protecting themselves against. We obtained four daily diary samples involving 2,794 participants who reported how hurt/rejected they felt by those they knew, how personally concerned they were about the spread of illness/COVID-19, and how vigilantly they engaged in self-protective behaviors to safeguard their health each day. An integrative data analysis revealed robust evidence that people who believed they were invulnerable to infectious disease engaged in more concerted efforts to protect themselves against the greater daily risk of contracting COVID-19 when being in acute social pain gave them added reason to see others as harmful to them. © The Author(s) 2022.
ABSTRACT
Background : Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccineinduced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/ml, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/ml;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/ml;p<0.0001) and uste (561U/ml;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/ml;p=0.62), nor between controls and vedo-treated patients (944U/ml;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusions : COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment. (Figure Presented) (Figure Presented)
ABSTRACT
INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.
ABSTRACT
Introduction: Emerging data suggests that seroresponse (SR) in patients with hematologic malignancy following COVID-19 vaccination is likely lower than in patients without blood cancer. The objective of this study was to perform a systematic review and meta-analysis on SR in patients with hematologic malignancy who received COVID-19 vaccination (submitted to PROSPERO for registration). Methods: We searched PubMed and EMBASE from December 1, 2020, to July 22, 2021, to identify studies of SR following COVID-19 vaccine in adult patients with hematologic malignancy (including studies in which patients with hematologic malignancy represented a subset of a broader population). Patients with positive serologic response at baseline (prior to vaccination) or known COVID-19 infection were excluded. The primary outcomes were pooled SR estimates following COVID-19 vaccination in patients with hematologic malignancy, and pooled SR estimates of subgroups based on hematologic malignancy type. Secondary outcomes were pooled relative risk ratio (RR;compared to non-cancer controls) based on dichotomous-effect SR in all patients, and subgroups based on hematologic malignancy type, treatment status, and use of anti-CD20 therapy. Pooled estimates and RR with its associated 95% confidence intervals (CIs) were calculated using MetaXL (EpiGear), and Reference Manager (Cochrane) using random effects model. Results A total of 17 studies comprising 2834 patients with hematologic malignancy from Europe, United Kingdom and North America were included (Figure 1). The pooled estimate for SR was 58% (95% CI 48-67%, I 2 95%), with a RR of 0.53 (95% 0.42-0.66, I 2 94%) when compared to controls (10 studies with comparison group, 1092 hematologic malignancy patients, 830 controls;Figure 2). The pooled estimate for SR varied by type of hematologic malignancy: lymphomas SR 52% (95% CI 36-68%, 7 studies, 832 patients, I 2 94%);chronic lymphocytic leukemia (CLL) SR 42% (95% CI 25-60%, 6 studies, 921 patients, I 2 93%);plasma cell dyscrasias SR 66% (95% CI 47-83%, 8 studies, 611 patients, I 2 95%);myeloproliferative neoplasms (MPNs, including chronic myelogenous leukemia) SR 83% (95% CI 68-95%, 6 studies, 227 patients, I 2 58%);acute leukemia SR 86% (95% CI 77-94%, 2 studies, 67 patients, 46 acute myelogenous leukemia [AML] and 15 acute lymphocytic leukemia], I 2 0%). The RR for SR also varied by type of hematologic malignancy: lymphomas (excluding CLL) RR 0.48 (95% CI 0.34-0.68, 4 studies, 337 patients, I 2 89%);CLL RR 0.37 (95% CI 0.25-0.53, 3 studies, 194 patients, I 2 54%);plasma cell dyscrasias RR 0.73 (95% CI 0.62-0.86, 5 studies, 323 patients, I 2 70%);RR MPN 0.78 (95% CI 0.62-0.99, 3 studies, 199 patients, I 2 90%). The pooled estimate for SR in those receiving treatment was 42% (95% CI 26-58%, 9 studies, 683 patients, I 2 94%). The pooled estimates for SR for those receiving anti-CD20, bruton tyrosine kinase inhibitor (BTKi), or venetoclax were 13% (95% CI 1-32%, 6 studies, 367 patients, I 2 88%), 42% (95% CI 17-71%, 3 studies, 319 patients, I 2 75%), and 20% (95% CI 0-54%, 3 studies, 39 patients, I 2 66%), respectively. The RR for those receiving treatment for their hematologic malignancy compared to those who were not receiving treatment was 0.51 (95% CI 0.37-0.71, 8 studies, 579 patients, I 2 89%;Figure 3). The RR of patients receiving anti-CD20 therapy compared to non-cancer controls was 0.13 (95% CI 0.02-0.93, 102 patients, I 2 73%). For patients treated with anti-CD20 therapy, the RR of those receiving vaccination within 9-12 months compared to beyond 9-12 months was 0.12 (95% CI 0.06-0.25, 2 studies, 74 patients, I 2 0%;Figure 4). Conclusion: Our systematic review and meta-analysis suggests that patients with hematologic malignancy have a lower SR rate following vaccination compared to controls. Furthermore, SR is variable across different types of hematologic malignancy, with very good response rates seen in patients with myeloid diseases (MPN and AML) and poor response rates seen in lymphoma and CLL. Active treatment, particu arly anti-CD20 therapy within 12 months of vaccination, is associated with a particularly low SR following vaccination. Additional studies are needed to understand non-humoral responses to vaccination, and to guide decisions regarding how to optimize vaccine response in patients with blood cancer. We plan to update the systematic review and meta-analysis as more data become available. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Background: The COVID-19 pandemic continues to pose complex problems across Europe and the world, with rising numbers of infections and the ongoing need for drastic public health interventions. This is difficult for patients with immune-mediated disorders like Inflammatory Bowel Disease (IBD), where immunosuppressive medications may affect susceptibility to serious infection. It was particularly challenging for physicians and patients during the first wave of the pandemic, when it was unclear whether anti-inflammatory flare treatment should be adapted to reduce infection risk, whilst trying to ensure symptomatic control and avoid admission to overwhelmed hospitals. Despite the development of various IBD / COVID-19 databases, the treatment adaptations and outcomes of patients experiencing IBD flares during the COVID-19 pandemic remain undefined. We aimed to compare IBD management and outcomes between pandemic and prepandemic cohorts. Methods: An observational cohort study was performed, comprising patients who contacted IBD teams for a symptom flare between March - June, 2020 in, 60 National Health Service trusts in the United Kingdom. Data were compared to a pre-pandemic cohort after propensity- matching for age and disease severity. Statistical analyses were performed using R (version, 4.1.0, Vienna, Austria). Results: In total, 3728 patients in the pandemic (n=1864) and pre-pandemic (n=1864) cohorts were included. The principal findings were reduced systemic corticosteroid prescription during the pandemic in both Crohn's disease (prednisolone: pandemic, 199/752, 26.5% vs, 263/708, 37.1%;p<0.001) and ulcerative colitis (UC) (prednisolone: pandemic, 372/1112, 33.5% vs, 470/1156, 40.7%, p<0.001), with increases in poorly bioavailable oral corticosteroids in Crohn's (pandemic, 117/752, 15.6% vs, 48/708, 6.8%;p<0.001) and UC (pandemic, 131/1112, 11.8% vs, 60/1156, 5.2%;p<0.001). Ustekinumab (Crohn's and UC) and vedolizumab (UC) treatment also significantly increased during the pandemic. Three-month steroid-free remission was similar in both Crohn's (pandemic, 175/616, 28.4% vs, 195/608, 32.1%;p=0.17) and UC (pandemic, 312/858, 36.4% vs, 404/1006, 40.2%;p=0.095). The, 65 patients experiencing a flare and COVID-19 were more likely to have moderate-to-severely active disease at three months compared to those with a flare alone. Conclusion: Despite several treatment adaptations during the pandemic, steroid-free outcomes were comparable to pre-pandemic levels, though patients with a flare and COVID-19 experienced worse outcomes. These findings have implications for IBD management during future waves or pandemics.
ABSTRACT
Background: Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/mL, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy- treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72- 4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusion: COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment.
ABSTRACT
Background: Predictors of severe infection and outcomes with COVID-19 in patients (pts) with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) are lacking. Pts with active disease may experience worse outcomes due to overall prognosis and cytopenias. Here we identify risk factors for severe COVID-19 infection and mortality in pts with AML, MDS, and ALL using the ASH RC COVID-19 Registry for Hematology. Methods: The ASH RC COVID-19 Registry for Hematology includes features and outcomes of a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection in adult pts with ongoing or a history of blood disorders. The Registry opened for data collection on April 1, 2020 and is a global effort housed on a secure data platform hosted by Prometheus Research, an IQVIA company. Data are made publicly available and regularly updated on the ASH RC website. Pt characteristics, outcomes, and predictors were analyzed and stratified by disease status (active initial diagnosis and relapsed/refractory vs. remission) and type of hematologic malignancy. Variables included age, comorbidities, type of hematologic malignancy (AML, MDS, ALL), neutrophil and lymphocyte count at time of COVID-19 diagnosis, and active treatment at the time of COVID-19 diagnosis. COVID-19 severity was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (ICU admission required). Categorical pt characteristics for each response group and associations between response groups and characteristics (i.e., alive vs. dead, severity vs. non-severity) were summarized by frequency with differences between response groups evaluated by Fisher's exact test and odds ratios with 95% confidence intervals (CIs) estimated by logistic regression. Multivariable analyses identified independent predictors of outcomes. Results: Analyses were conducted on data from 257 pts with AML (n=135), MDS (n=40), and ALL (n=82);46% were in remission and 44% had active disease (10% unknown). Overall mortality from COVID-19 infection was 21%. Pts with active disease were significantly more likely to present with moderate and severe COVID-19 compared to those in remission (remission vs. active disease, severe 33% (n=20) vs. 67%(n=40), moderate 45% (n=35) vs.55% (n=42), and mild: 67% (n=56) vs. 33% (n=28), p value <0.001) (Figure 1). This was significant when categorized as severe vs. non severe as well (p=0.002). COVID-19 severity was also associated with AML diagnosis, major comorbidities, and neutropenia and lymphopenia at the time of COVID-19 diagnosis. Univariate analyses of increased mortality after COVID-19 diagnosis were significantly associated with advanced age, male sex, pre-diagnosis survival < 6 months, active disease status, neutropenia, lymphopenia and forgoing ICU care. Multivariable analyses in all pts (Figure 1), revealed that increased COVID-19 related mortality was significantly associated with neutropenia at diagnosis (OR 3.15, 95% C.I. 1.31-8.08, p=0.01), estimated pre-COVID-19 prognosis of < 6 months (OR 8.58, 95% C.I. 3.24-24.46, p<0.001) and forgoing ICU care (OR 6.66, 95% C.I. 2.56-18.23, p<0.001). Among hospitalized pts, increased COVID-19 mortality was associated with estimated pre-COVID-19 prognosis of < 6 months (OR 6.77, 95% C.I. 2.34-22.24, p<0.001) and forgoing ICU care (OR 3.98, 95% C.I. 1.45-11.66, p=0.007). Pts who were older, male, smokers, with active disease, or estimated to have pre-COVID-19 survival of < 6 months were more likely to forgo ICU care. Forgoing ICU care (n=37,16%) was associated with a higher COVID-19 mortality in all pts (n=234, OR 15.6, 95% C.I. 6.4-40.9, p<0.001), hospitalized pts (n=143, OR 9.2, 95% C.I., 3.5-26.5, p<0.001) and in pts where ICU admission was indicated and declined (n=61 OR 5.6, 95% C.I. 1.1-56.4, p=0.03)). Neither active disease status nor ongoing cancer treatment were associated with increased mortality among hospitalized patients. Conclusions: These data suggest that patients with active disease experience significantly higher COVID-19 severity but not increased mortality from COVID-19. Patients who had neutropenia and a pre-COVID-19 prognosis of < 6 months had higher mortality from COVID-19 infection and may be more likely to forgo ICU care. If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate regardless of remission status. [Formula presented] Disclosures: Desai: Agios: Consultancy;Janssen R&D: Research Funding;Kura Oncology: Consultancy;Bristol Myers Squibb: Consultancy;Astex: Research Funding;Takeda: Consultancy. Goldberg: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Aprea: Research Funding;Prelude Therapeutics: Research Funding;Pfizer: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Honoraria;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Arog: Research Funding;Celularity: Research Funding;Aptose: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Neuberg: Pharmacyclics: Research Funding;Madrigal Pharmaceuticals: Other: Stock ownership. Radhakrishnan: Emcure Pharmaceuticals: Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Astrazeneca: Consultancy, Honoraria;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Pfizer: Consultancy, Honoraria;Johnson and Johnson: Honoraria;Novartis: Honoraria;Aurigene: Speakers Bureau;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Amgen: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Consultancy;Blueprint Medicines: Consultancy;Astex: Consultancy;Janssen: Research Funding;Daiichi Sankyo: Consultancy;Jazz: Consultancy;Agios: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Otsuka: Consultancy;Astellas: Consultancy;Helsinn: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Jasper Therapeutics: Consultancy;Bristol Myers Squibb: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Sehn: Novartis: Consultancy;Genmab: Consultancy;Debiopharm: Consultancy. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Syros: Membership on an entity's Board of Directors or advisory committees;Kura: Membership on an entity's Board of Directors or advisory committees;NYU Grand Rounds: Honoraria;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria. Wood: Pfizer: Research Funding;Teladoc: Consultancy;Koneksa Health: Consultancy, Current equity holder in publicly-traded company.
ABSTRACT
Introduction Endoscopy services were paused during the first wave of the COVID-19 pandemic between March - April 2020. Endoscopy resumed in May 2020 at a reduced productivity alongside early clinical triage in an effort to use resources responsibly. We assessed whether our reduced service led to reductions in gastrointestinal (GI) cancer detection. We assessed differences in the choice of initial investigation, clinical triage and referral to endoscopy time among GI cancers diagnosed via the suspected GI cancer referral pathway. Methods GI cancer diagnoses were reviewed retrospectively over a seven month period (Mar-Oct 2020). Inclusion criteria were patients coded with a new diagnosis of GI cancer. The volume of endoscopic procedures performed was assessed using our endoscopy reporting software. Results were compared to the equivalent time period in 2019. Differences in time to endoscopy (days) were evaluated with a two-sample unpaired t-test. Results There was a 28.5% reduction in GI cancer diagnoses in 2020 (Mar-Oct) compared to 2019 (191 vs 267), with a 27.1% reduction in GI cancers diagnosed via endoscopic procedures (132 vs 181). There was a 42.7% reduction in endoscopic procedures in 2020 (Mar-Oct) compared to 2019 (6977 vs 12186). In terms of referrals for suspected GI cancers from GPs, there was a 30% reduction (3188 vs 4579). In 2020 (Mar-Oct), among cancers diagnosed via endoscopic procedures on the suspected GI cancer pathway, 40 of 68 (58.8%) patients had imaging as their first investigation (n=5 Barium swallow, n=13 CT abdomen, n=22 CT colonography) compared to 21 of 81 (25.9%) patients in 2019 (n=11 CT abdomen, n=9 CT colonography). Following the start of clinical triage (May-Oct 2020), 36 of 54 (67%) patients were triaged as 'very urgent'. 17 of 54 (31%) patients were triaged as 'urgent'. 1 patient was not prioritised as their barium swallow suggested a diagnosis of achalasia which was later found to be an oesophageal malignancy (referral to endoscopy 95 days). There was no significant difference in referral to endoscopy time in 2020 (Mar-Oct) [mean 45 days, SD 40.2] compared to 2019 [mean 41.6 days, SD 26.7] (mean difference 3.4 days p=0.55). Conclusions The COVID-19 pandemic has led to a 28.5% reduction in GI cancer diagnoses. This worrying reduction in cancer detection will need to be ameliorated by an increase in endoscopy capacity. Radiological investigations were utilised more during this period to assess suspected GI cancer referrals. 98% of cancer patients were appropriately prioritised as very urgent or urgent based on clinical triage, and radiological investigations aided in triage. There was no significant difference in referral to endoscopy time. We highlight that achalasia diagnosed on barium swallow should always visualised directly, even with curtailed endoscopy capacity.