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1.
Inflamm Bowel Dis ; 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1931837

ABSTRACT

We demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.

2.
Am J Gastroenterol ; 117(3): 462-469, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1625333

ABSTRACT

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Ad26COVS1 , BNT162 Vaccine , COVID-19/prevention & control , Immunity, Humoral/physiology , Inflammatory Bowel Diseases/immunology , Adult , Age Factors , Cohort Studies , Female , Humans , Immunologic Factors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged , Odds Ratio , Risk Factors , Sex Factors , Tumor Necrosis Factor Inhibitors/therapeutic use
3.
Inflamm Bowel Dis ; 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1556255

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. METHODS: We evaluated coronavirus disease 2019 (COVID-19) vaccine-related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. RESULTS: A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. CONCLUSIONS: Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.


The severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with inflammatory bowel disease (IBD). Severe localized and systemic vaccine-related adverse events were rare, and rates of IBD flare were low (2%) following severe acute respiratory syndrome coronavirus 2 vaccination in a cohort of 3316 participants with IBD.

4.
Clin Gastroenterol Hepatol ; 20(8): 1831-1838, 2022 08.
Article in English | MEDLINE | ID: covidwho-1517086

ABSTRACT

BACKGROUND & AIMS: Integrated inflammatory bowel disease (IBD) care is effective but not routinely implemented. Validated methods that simultaneously address mind and body targets such as resilience may improve access and outcomes. We describe the development and implementation of the GRITT method and its impact on resilience, health care utilization (HCU), and opioid use in IBD. METHODS: Consecutive patients from an academic IBD center were evaluated for low resilience on the basis of provider referral. Low resilience patients were invited to participate in the GRITT program. Primary outcome was % reduction in HCU. Secondary outcomes were change in resilience and corticosteroid and opioid use. Patients were allocated into 2 groups for analysis: GRITT participants (GP) and non-participants (NP). Clinical data and HCU in the year before enrollment were collected at baseline and 12 months. One-way repeated measures multivariate analysis of covariance evaluated group × time interactions for the primary outcome. Effect size was calculated for changes in resilience over time. RESULTS: Of 456 screened IBD patients 394 were eligible, 184 GP and 210 NP. GP had greater reduction in HCU than NP: 71% reduction in emergency department visits, 94% reduction in unplanned hospitalizations. There was 49% reduction in opioid use and 73% reduction in corticosteroid use in GP. Resilience increased by 27.3 points (59%), yielding a large effect size (d = 2.4). CONCLUSIONS: Mind-body care that focuses on building resilience in the context of IBD care may be a novel approach to reduce unplanned HCU and opioid use, but large, multicenter, randomized controlled trials are needed.


Subject(s)
Analgesics, Opioid , Inflammatory Bowel Diseases , Analgesics, Opioid/therapeutic use , Chronic Disease , Hospitalization , Humans , Inflammatory Bowel Diseases/drug therapy , Patient Acceptance of Health Care
6.
Sci Rep ; 11(1): 13308, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281741

ABSTRACT

Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.


Subject(s)
COVID-19 , Feces , Gastrointestinal Microbiome , Nasopharynx/virology , RNA, Viral/isolation & purification , Aged , Biomarkers/metabolism , COVID-19/epidemiology , COVID-19/immunology , Cohort Studies , Cytokines/metabolism , Feces/virology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Male , Middle Aged , New York City/epidemiology , SARS-CoV-2/isolation & purification
9.
Gastroenterology ; 160(1): 287-301.e20, 2021 01.
Article in English | MEDLINE | ID: covidwho-796100

ABSTRACT

BACKGROUND AND AIMS: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes. METHODS: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment. RESULTS: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. Commonly used IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines. In addition, we have defined molecular responses to COVID-19 infection that are also enriched in IBD, pointing to shared molecular networks between COVID-19 and IBD. CONCLUSIONS: These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. Preprint doi: https://doi.org/10.1101/2020.05.21.109124.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/enzymology , Inflammatory Bowel Diseases/enzymology , Intestinal Mucosa/enzymology , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Case-Control Studies , Clinical Trials as Topic , Cross-Sectional Studies , Disease Models, Animal , Female , Gene Regulatory Networks , Host-Pathogen Interactions , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Intestinal Mucosa/drug effects , Intestinal Mucosa/virology , Longitudinal Studies , Male , Mice , SARS-CoV-2/drug effects , Serine Endopeptidases/genetics , Signal Transduction
10.
J Pediatr Gastroenterol Nutr ; 71(2): 153-155, 2020 08.
Article in English | MEDLINE | ID: covidwho-729245

ABSTRACT

Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor-alpha (TNF-α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 polymerase chain reaction was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID-19 requires further investigation.


Subject(s)
Coronavirus Infections/drug therapy , Crohn Disease/complications , Genetic Diseases, X-Linked/complications , Ichthyosiform Erythroderma, Congenital/complications , Infliximab/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Limb Deformities, Congenital/complications , Pneumonia, Viral/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Abnormalities, Multiple , Adolescent , Antirheumatic Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Humans , Male , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Tumor Necrosis Factor-alpha/blood
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