Antibody Responses to SARS-CoV-2 After Infection or Vaccination in Children and Young Adults With Inflammatory Bowel Disease

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 (n = 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.

Protective SARS-CoV-2 Antibody Response in Children With Inflammatory Bowel Disease

“…They are also in line with a recent study reporting a high rate of seroconversion (85%) in immunocompromised PIBD patients ( n = 12, median age 10 years, range 2–17 years) at a median time of 8 weeks after SARS-CoV-2 infection ( 46 ). Our results differ, however, from the study of Dailey et al who reported lower titers of anti-SARS-CoV-2 S-RBD antibodies in pediatric and young adult IBD patients ( n = 44, median age 18 years, range 11–26 years) in comparison to a control group of non-IBD children and adults ( 47 ). The different outcome may be related to the diverse characteristics of control groups: in the study of Dailey's et al control subjects consisted of non-IBD children hospitalized with SARS-CoV-2 infection and of non-IBD adults with mild to moderate COVID-19, while we compared PIBD patients 1:4 to healthy children matched for age, sex, and COVID-19 severity.…”

“…Moreover, independently from the ongoing IBD treatment, the titer of anti-spike antibodies resulted similar to a control population of healthy children matched for age, sex, and COVID-19 severity. These results are in agreement with the observation that immunocompromised adult IBD patients with COVID-19 can develop a serologic response comparable to that of agematched healthy controls (45) Contrarily to adult IBD reports (9) but similarly to another PIBD study (47), we did not observe different levels of anti-SARS-CoV-2 antibodies between children treated with anti-TNFs and children receiving other biologics or immunomodulatory drugs, probably due to the small size of our patient population. We also did not observe serological differences relative to COVID-19 severity since all patients in our cohort had a mild form of disease.…”

“…Moreover, none of the PIBD patients experiencing a disease flare during the study period tested positive for SARS-CoV-2. These results are in agreement with those of a single, recent, study reporting that no children with IBD (n = 44) suffered a disease flare following SARS-CoV-2 infection (47).…”

“…How long these antibodies persist after infection in exogenously immunocompromised subjects is still under investigation ( 36 ). In our cohort of children with IBD, we detected anti-SARS-CoV-2 S-RBD IgG at 3 months after COVID-19, consistently with the observation of detectable anti-SARS-CoV-2 antibodies up to 2 months after infection in adult and pediatric IBD patients treated with biologics ( 47 , 48 ). We did not investigate the kinetic of antibody response over time.…”

“…Contrarily to adult IBD reports ( 9 ) but similarly to another PIBD study ( 47 ), we did not observe different levels of anti-SARS-CoV-2 antibodies between children treated with anti-TNFs and children receiving other biologics or immunomodulatory drugs, probably due to the small size of our patient population. We also did not observe serological differences relative to COVID-19 severity since all patients in our cohort had a mild form of disease.…”