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. 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 expressing HEK-293 cells was used. Results: 436 patients were enrolled (mean age 17 years, range 2-26 years, 58% male, 71% Crohn disease, 29% ulcerative colitis, IBD-unspecified). 44 (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 to natural infection, and all developed neutralizing antibodies to both wild type and variant SARS-CoV-2. Conclusions and Relevance: 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.

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…The vast majority of included studies evaluated vaccines developed by Pfizer (BNT162b2) or Moderna (mRNA-1273). Thirteen studies included patients who received the vaccine developed by Janssen (Ad26.COV2.S) [ [25] , [26] , [27] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] ], nine included patients vaccinated with the AstraZeneca vaccine (ChAdOx1) [ [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] ], three included patients receiving the CoronaVac vaccine (Sinovac Biotech) [ [50] , [51] , [52] ], and one randomized controlled trial evaluated the vaccine developed by Novavax (NVX-CoV2373) vaccine [ 53 ]. One study included patients receiving the BBV152-Covaxin (Bharat Biotech) vaccine [ 44 ] and one included patients receiving the BBIBP-CorV (Sinopharm) vaccine [ 54 ].…”

“…Thirty-one studies reported immunogenicity in 4680 patients with inflammatory immune-mediated diseases ( Table S6 ) [ 27 , 28 , 32 , 36 , 37 , 39 , [45] , [46] , [47] , 50 , 51 , 54 , 55 , 82 , [161] , [162] , [163] , [164] , [165] , [166] , [167] , [168] , [169] , [170] , [171] , [172] , [173] , [174] , [175] , [176] , [177] , [178] ]. Main represented groups included rheumatoid arthritis ( n = 665), inflammatory bowel diseases ( n = 476) and multiple sclerosis ( n = 231).…”

“…Main represented groups included rheumatoid arthritis ( n = 665), inflammatory bowel diseases ( n = 476) and multiple sclerosis ( n = 231). Twenty of those studies had a control group [ 32 , 37 , [45] , [46] , [47] , 50 , 51 , 55 , [161] , [162] , [163] , [164] , 166 , 167 , 169 , 171 , 172 , 174 , 177 , 178 ] ( n = 1609), among which 16 participants failed to mount a post-vaccine antibody response [ 47 , 50 , 51 , 55 , 163 , 164 ].…”

“…found high rates (respectively 47% and 50%) in patients with multiple sclerosis (MS) [ 164 , 168 ]. Six studies tested participants' sera with neutralization assays [ 32 , 37 , 51 , 163 , 172 , 174 ], one tested neutralization on a SARS-CoV-2 spike protein bearing the N501Y mutation (present in the alpha variant) [ 32 ]. Two studies provided non-response rates which were either the same as with anti-S IgG assay (0%, 0/26 [ 172 ]) or higher (44%, 375/859 vs. 29%, 245/859 with the anti-S assay [ 51 ]).…”

Comparison of SARS-CoV-2 Antibodies and Six Immunoassays in Pediatric and Adult Patients 12 Weeks After COVID-19

“…Besides, SARS-CoV-2 serological tests were mostly evaluated in adults, so we have limited knowledge of pediatric patients. The studies that compared antibody levels of both children and adults are limited [11][12]. Recently, evidence of natural immunity to SARS-CoV-2 in children has drawn attention as a parameter that may help diagnose multisystem inflammatory syndrome in children (MIS-C or MIS-A in adults) [13].…”