ABSTRACT
BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial. METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and high-throughput neutralization assay that incorporates SARS-CoV-2 spike protein onto a lentivirus and measures pseudoviral entry into ACE2-angiotensin converting enzyme 2 (ACE2) expressing human embryonic kidney 293 (HEK-293) cells was used. RESULTS: There were 436 patients enrolled (mean age, 17 years, range 2-26 years; 58% male; 71% Crohn's disease, 29% ulcerative colitis, IBD-unspecified). Forty-four (10%) of enrolled subjects had SARS-CoV-2 S-RBD IgG antibodies. Compared to non-IBD adults (ambulatory) and hospitalized pediatric patients with PCR documented SARS-CoV-2 infection, S-RBD IgG antibody levels were significantly lower in the IBD cohort and by 6 months post infection most patients lacked neutralizing antibody. Following vaccination (nâ =â 33), patients had a 15-fold higher S-RBD antibody response in comparison with natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2. CONCLUSIONS: The lower and less durable SARS-CoV-2 S-RBD IgG response to natural infection in IBD patients receiving biologics puts them at risk of reinfection. The robust response to immunization is likely protective.
Subject(s)
Antibody Formation , COVID-19 Vaccines , COVID-19 , Inflammatory Bowel Diseases , Adolescent , Adult , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Child , Child, Preschool , Female , HEK293 Cells , Humans , Immunoglobulin G , Inflammatory Bowel Diseases/drug therapy , Longitudinal Studies , Male , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Young AdultABSTRACT
Objectives and Study: SARS-CoV-2, a novel coronavirus causing the pandemic clinical disease COVID-19, is generally associated with mild disease in most young patients with inflammatory bowel disease (IBD) despite their receiving immunosuppressive therapy. The aim of this study was to longitudinally evaluate characteristics of clinical and serologic response to SARS-CoV-2 infection in a cohort of young patients with IBD receiving biologics. Methods: Starting May 2020 we obtained serum on patients with IBD at the time of infusion with either infliximab or vedolizumab, along with baseline demographic and clinical data, as well possible SARSCoV2 exposure history (patient, family member). To measure antibodies to SARS-CoV-2, we used a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. We immobilized biotinylated SARS-CoV-2 Spike protein receptor binding domain (S-RBD) or Nucleocapsid protein of SARS-CoV-2 (N) to detect specific IgG antibodies to the virus in patient serum. Spike protein-RBD-specific antibodies were detectable in serial dilutions up to 100,000-fold of serum samples. Titration curves from COVID-19 convalescent and healthy controls were used to normalize the area under the curve (AUC) values to quantitate the antibody levels. Antibody isotypes were measured using anti-Ig (IgG, IgA, IgM, IgG1-4) specific secondary antibodies conjugated to a fluorescent tag. We used a sensitive and high throughput SARS-CoV-2 neutralization assay using a lentivirus that expresses Spike protein to assess specific inhibition of viral entry. The results shown reflect the first serum sample obtained from unique patients. Results: 410 subjects were studied (mean age 17 years, 59% male, 305 (74%) Crohn's disease, 105 (25%) ulcerative colitis/IBD-U, 341 (83%) on infliximab, 69 (17%) vedolizumab, 13% concomitant methotrexate. 27/410 (6.6%) were positive for S-RBD and Nucleocapsid specific IgG. AUC values varied from 3150 to 285724 (Fig 1). S-RBD specific IgA+ 4/27 (15%) and IgG1+ 20/27 (74%) were found. Other isotypes undetectable. Patients' serum efficiently neutralized the virus at up to 10,000-fold serial dilution in only 10/27 (37%). (Fig 2). No differences in age, gender, diagnosis, or specific therapies were noted for (+) vs (-) anti-SARS-CoV-2 antibody status. 13/27 (48%) patients were asymptomatic. Non-exclusive symptoms were rhinorrhea 9 (33%), headache 8 (30%), sore throat 4 (15%). cough 4 (15%), diarrhea 4 (15%), chills 3 (11%), loss of smell/taste 2 (7%), fever 1 (4%). No patient was hospitalized. 4 (15%) had a family member with PCR+ COVID-19. Conclusions: We found a significant prevalence of anti SARS-CoV-2 antibody in our IBD population with the majority of + patients having non-neutralizing antibody. The role of biologics in mitigating clinical and serologic response to SARS-CoV-2 requires exploration.