RESUMEN
Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedades Inflamatorias del Intestino , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/inmunología , Medición de RiesgoAsunto(s)
Vacunas contra la COVID-19/administración & dosificación , COVID-19/inmunología , COVID-19/prevención & control , Inmunización Secundaria/métodos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , Niño , Humanos , Esquemas de Inmunización , Inmunización Secundaria/normas , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Reino Unido , Adulto JovenRESUMEN
The recent emergency use authorization of a third COVID-19 vaccine means that most patients with inflammatory bowel disease (IBD) will soon be eligible to be vaccinated. Gastroenterology clinicians should be prepared to address patients' concerns regarding safety and efficacy of vaccines. They should also strongly recommend that all their patients be vaccinated with a COVID-19 vaccine. Additionally, they should be prepared to educate patients about logistics that will result in successful vaccination completion. All these measures will be crucial to ensure high uptake among their patients with IBD.
Asunto(s)
Vacunas contra la COVID-19/farmacología , COVID-19 , Gastroenterólogos , Enfermedades Inflamatorias del Intestino , Vacunación , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/psicología , Participación del Paciente/métodos , Participación del Paciente/psicología , Rol del Médico , Servicios Preventivos de Salud , Medición de Riesgo , SARS-CoV-2 , Vacunación/métodos , Vacunación/psicología , Cobertura de Vacunación/métodosRESUMEN
Alu retrotransposons belong to the class of short interspersed nuclear elements (SINEs). Alu RNA is abundant in cells and its repetitive structure forms double-stranded RNAs (dsRNA) that activate dsRNA sensors and trigger innate immune responses with significant pathological consequences. Mechanisms to prevent innate immune activation include deamination of adenosines to inosines in dsRNAs, referred to as A-to-I editing, degradation of Alu RNAs by endoribonucleases, and sequestration of Alu RNAs by RNA binding proteins. We have previously demonstrated that widespread loss of Alu RNA A-to-I editing is associated with diverse human diseases including viral (COVID-19, influenza) and autoimmune diseases (multiple sclerosis). Here we demonstrate loss of A-to-I editing in leukocytes is also associated with inflammatory bowel diseases. Our structure-function analysis demonstrates that ability to activate innate immune responses resides in the left arm of Alu RNA, requires a 5'-PPP, RIG-I is the major Alu dsRNA sensor, and A-to-I editing disrupts both structure and function. Further, edited Alu RNAs inhibit activity of unedited Alu RNAs. Altering Alu RNA nucleotide sequence increases biological activity. Two classes of Alu RNAs exist, one class stimulates both IRF and NF-kB transcriptional activity and a second class only stimulates IRF transcriptional activity. Thus, Alu RNAs play important roles in human disease but may also have therapeutic potential.
Asunto(s)
Elementos Alu/genética , Elementos Alu/inmunología , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Adenosina , COVID-19 , Humanos , Inosina , ARN Bicatenario/genética , ARN Bicatenario/inmunología , SARS-CoV-2RESUMEN
Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.
Asunto(s)
Artritis Reumatoide/terapia , Infecciones Bacterianas/prevención & control , Terapia Biológica/efectos adversos , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/terapia , Inhibidores de las Cinasas Janus/efectos adversos , Virosis/prevención & control , Artritis Reumatoide/inmunología , COVID-19/etiología , Hepatitis A/prevención & control , Hepatitis B/prevención & control , Herpes Zóster/prevención & control , Humanos , Enfermedades Inflamatorias del Intestino/inmunología , Gripe Humana/prevención & control , Infecciones Neumocócicas/prevención & control , Factores de Riesgo , Tuberculosis Pulmonar/prevención & control , Cobertura de Vacunación , Vacunas de Productos Inactivados/administración & dosificaciónRESUMEN
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.
Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , Ad26COVS1 , Vacuna BNT162 , COVID-19/prevención & control , Inmunidad Humoral/fisiología , Enfermedades Inflamatorias del Intestino/inmunología , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Factores Sexuales , Inhibidores del Factor de Necrosis Tumoral/uso terapéuticoAsunto(s)
Unión Europea/organización & administración , Gastroenterología/estadística & datos numéricos , Sociedades Médicas/organización & administración , Vacuna nCoV-2019 mRNA-1273/farmacología , Administración Intravenosa , Profilaxis Antibiótica/métodos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Colecistectomía/métodos , Colecistectomía/normas , Ensayos Clínicos como Asunto , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn , Tratamiento de Urgencia , Endoscopía/métodos , Gastroenterología/organización & administración , Gastroparesia/cirugía , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Miotomía/métodos , Cuidados Preoperatorios , Inducción de Remisión , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Interfaz Usuario-ComputadorAsunto(s)
COVID-19 , Enfermedades Inflamatorias del Intestino , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/inmunología , SARS-CoV-2 , Vacunas Sintéticas , Vacunas de ARNmAsunto(s)
COVID-19/prevención & control , Microbioma Gastrointestinal/inmunología , Hipótesis de la Higiene , Enfermedades Inflamatorias del Intestino/etiología , Salud Global/tendencias , Humanos , Higiene , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Factores de RiesgoAsunto(s)
Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Inmunosupresores/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , COVID-19/inmunología , COVID-19/virología , Vacunas contra la COVID-19/efectos adversos , Toma de Decisiones Clínicas , Humanos , Huésped Inmunocomprometido , Enfermedades Inflamatorias del Intestino/inmunología , Vacunas contra la Influenza/efectos adversos , Gripe Humana/inmunología , Gripe Humana/virología , Vacunación Masiva/efectos adversos , Medición de Riesgo , Factores de Riesgo , Estaciones del AñoRESUMEN
BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas â¼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (â¼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.
Asunto(s)
Vacuna BNT162/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/inmunología , Inhibidores del Factor de Necrosis Tumoral/inmunología , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Israel , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/inmunologíaAsunto(s)
Terapia Biológica/efectos adversos , Vacunas contra la COVID-19 , COVID-19/inmunología , Huésped Inmunocomprometido , Enfermedades Inflamatorias del Intestino/inmunología , Cobertura de Vacunación/estadística & datos numéricos , Negativa a la Vacunación/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , COVID-19/prevención & control , Femenino , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Reino UnidoAsunto(s)
Vacuna nCoV-2019 mRNA-1273/inmunología , Anticuerpos Antivirales/sangre , Vacuna BNT162/inmunología , COVID-19/prevención & control , Huésped Inmunocomprometido , Enfermedades Inflamatorias del Intestino/inmunología , Adulto , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Persona de Mediana Edad , SARS-CoV-2Asunto(s)
Infecciones Asintomáticas/epidemiología , Productos Biológicos/efectos adversos , COVID-19/epidemiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , SARS-CoV-2/aislamiento & purificación , Adulto , COVID-19/sangre , COVID-19/inmunología , COVID-19/virología , Prueba Serológica para COVID-19/estadística & datos numéricos , Estudios de Cohortes , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/inmunología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , SARS-CoV-2/inmunología , Estudios SeroepidemiológicosRESUMEN
BACKGROUND & AIMS: Patients with immune-mediated inflammatory diseases (IMIDs) have an increased risk of coronavirus disease 2019 (COVID-19), primarily attributed to the use of immunosuppressive drugs such as glucocorticoids, which may attenuate the response to vaccines. This meta-analysis assessed the serologic response to COVID-19 vaccination in patients with IMIDs. METHODS: Electronic databases were searched on August 1, 2021, for observational studies. Data extracted included reference population, medications, vaccination, and proportion of patients achieving a serologic response. RESULTS: The analysis included 25 observational studies (5360 patients). Most of the studies used messenger RNA (mRNA) vaccines (BNT162b2, mRNA-1273), with a small number of studies including other types of vaccines (AZD1222, CoronaVac, BBV152, Ad26.COV2.S). Serologic response after 1 dose (6 studies) and 2 doses (17 studies) of mRNA vaccine were 73.2% (95% confidence interval [CI], 65.7%-79.5%) and 83.4% (95% CI, 76.8%-88.4%), respectively. On meta-regression, anti-CD20 therapy was associated with lower response rates (P < .001) and anti-tumor necrosis factor therapy also showed a trend toward lower response rates (P = .058). Patients with IMIDs were less likely to achieve a serologic response compared with controls after 2 doses of mRNA vaccine (6 studies; odds ratio, 0.086; 95% CI, 0.036-0.206; P < .001). There were not enough studies to assess response to the adenoviral or inactivated vaccines. CONCLUSIONS: Our meta-analysis demonstrated that patients with IMIDs have a reduced response to mRNA COVID-19 vaccines. These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine.
Asunto(s)
Vacunas contra la COVID-19/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Reumáticas/inmunología , Vacunación , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna BNT162/inmunología , HumanosRESUMEN
Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.
Asunto(s)
Bacterias/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Inmunoglobulina A/uso terapéutico , Agentes Inmunomoduladores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Intestinos/efectos de los fármacos , Animales , Bacterias/inmunología , Disbiosis , Interacciones Huésped-Patógeno , Humanos , Inmunoglobulina A/efectos adversos , Agentes Inmunomoduladores/efectos adversos , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Intestinos/inmunología , Intestinos/microbiología , Especificidad de la EspecieRESUMEN
Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is threatening global health worldwide with unprecedented contagiousness and severity. The best strategy to overcome COVID-19 is a vaccine. Various vaccines are currently being developed, and mass vaccination is in progress. Despite the very encouraging clinical trial results of these vaccines, there is insufficient information on the safety and efficacy of vaccines for inflammatory bowel disease (IBD) patients facing various issues. After reviewing current evidence and international guidelines, the Korean Association for the Study of Intestinal Diseases (KASID) developed an expert consensus statement on COVID-19 vaccination issues for Korean IBD patients. This expert consensus statement emphasizes that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination be strongly recommended for IBD patients, and it is safe for IBD patients receiving immunomodulatory therapy.