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1.
J Pediatr Gastroenterol Nutr ; 70(6): 727-733, 2020 06.
Article in English | MEDLINE | ID: covidwho-1722710

ABSTRACT

INTRODUCTION: With the current coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised about the risk to children with inflammatory bowel diseases (IBD). We aimed to collate global experience and provide provisional guidance for managing paediatric IBD (PIBD) in the era of COVID-19. METHODS: An electronic reporting system of children with IBD infected with SARS-CoV-2 has been circulated among 102 PIBD centres affiliated with the Porto and Interest-group of ESPGHAN. A survey has been completed by major PIBD centres in China and South-Korea to explore management during the pandemic. A third survey collected current practice of PIBD treatment. Finally, guidance points for practice have been formulated and voted upon by 37 PIBD authors and Porto group members. RESULTS: Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. No cases have been reported in China and South Korea but biologic treatment has been delayed in 79 children, of whom 17 (22%) had exacerbation of their IBD. Among the Porto group members, face-to-face appointments were often replaced by remote consultations but almost all did not change current IBD treatment. Ten guidance points for clinicians caring for PIBD patients in epidemic areas have been endorsed with consensus rate of 92% to 100%. CONCLUSIONS: Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other.


Subject(s)
Coronavirus Infections/therapy , Inflammatory Bowel Diseases/therapy , Pneumonia, Viral/therapy , Adolescent , Adult , Betacoronavirus , COVID-19 , Child , Consensus , Coronavirus Infections/chemically induced , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Health Care Surveys , Humans , Immunologic Factors/adverse effects , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Pandemics , Pneumonia, Viral/chemically induced , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Severity of Illness Index
2.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
3.
J Crohns Colitis ; 15(4): 687-691, 2021 Apr 06.
Article in English | MEDLINE | ID: covidwho-1387845

ABSTRACT

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15-80 µg/L], C-reactive protein [CRP] [ >100mg/L for  >10 days, normal 0-5 mg/L], erythrocyte sedimentation rate [ESR] consistently  >100mm/h [normal 0-15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.


Subject(s)
COVID-19/diagnosis , Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Infliximab/therapeutic use , Systemic Inflammatory Response Syndrome/diagnosis , COVID-19/complications , COVID-19/therapy , Child , Colitis, Ulcerative/complications , Female , Humans , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/therapy
4.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1146071

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
5.
Arch Dis Child ; 105(12): 1186-1191, 2020 12.
Article in English | MEDLINE | ID: covidwho-690253

ABSTRACT

BACKGROUND: COVID-19 has impacted on healthcare provision. Anecdotally, investigations for children with inflammatory bowel disease (IBD) have been restricted, resulting in diagnosis with no histological confirmation and potential secondary morbidity. In this study, we detail practice across the UK to assess impact on services and document the impact of the pandemic. METHODS: For the month of April 2020, 20 tertiary paediatric IBD centres were invited to contribute data detailing: (1) diagnosis/management of suspected new patients with IBD; (2) facilities available; (3) ongoing management of IBD; and (4) direct impact of COVID-19 on patients with IBD. RESULTS: All centres contributed. Two centres retained routine endoscopy, with three unable to perform even urgent IBD endoscopy. 122 patients were diagnosed with IBD, and 53.3% (n=65) were presumed diagnoses and had not undergone endoscopy with histological confirmation. The most common induction was exclusive enteral nutrition (44.6%). No patients with a presumed rather than confirmed diagnosis were started on anti-tumour necrosis factor (TNF) therapy.Most IBD follow-up appointments were able to occur using phone/webcam or face to face. No biologics/immunomodulators were stopped. All centres were able to continue IBD surgery if required, with 14 procedures occurring across seven centres. CONCLUSIONS: Diagnostic IBD practice has been hugely impacted by COVID-19, with >50% of new diagnoses not having endoscopy. To date, therapy and review of known paediatric patients with IBD has continued. Planning and resourcing for recovery is crucial to minimise continued secondary morbidity.


Subject(s)
COVID-19 , Child Health Services , Endoscopy, Gastrointestinal , Health Services Accessibility , Inflammatory Bowel Diseases , Tumor Necrosis Factor Inhibitors/therapeutic use , Adolescent , Ambulatory Care Facilities/statistics & numerical data , Ambulatory Care Facilities/supply & distribution , COVID-19/epidemiology , COVID-19/prevention & control , Child , Child Health Services/statistics & numerical data , Child Health Services/supply & distribution , Communicable Disease Control/methods , Endoscopy, Gastrointestinal/methods , Endoscopy, Gastrointestinal/statistics & numerical data , Enteral Nutrition/methods , Enteral Nutrition/statistics & numerical data , Female , Health Care Surveys , Health Services Accessibility/standards , Health Services Accessibility/statistics & numerical data , Health Services Needs and Demand , Humans , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/therapy , Male , SARS-CoV-2 , United Kingdom/epidemiology
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