ABSTRACT
Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by immune dysregulation and decreased T cell receptor (TCR) repertoire diversity. Patients with immune-mediated disorders such as IBD have attenuated convalescent antibody responses after COVID-19 infection. We sought to understand the immune configuration associated with high versus low convalescent SARS-CoV- 2 antibodies in patients with IBD using single-cell immunophenotyping. Methods: We performed a study of 9 patients with IBD who were SARS-CoV-2 convalescent (recovered from COVID-19 and converted RNA positive to negative) and 9 matched SARS-CoV-2 naïve controls (no prior COVID-19, confirmed RNA negative). We measured plasma SARS-CoV- 2 antibody (N protein IgG, S1RBD IgG, S1RBD IgA) levels from patients with IBD two months after recovering from COVID-19 (RNA negative). We selected three patients with the highest SARS-CoV-2 antibodies and three matched (for age, sex, IBD subtype and disease activity, medications, COVID-19 severity) patients with the lowest antibodies and performed their peripheral blood mononuclear cell (PBMC) single-cell transcriptomics with paired TCR and BCR sequencing using 10X Genomics. Normalization, dimensionality reduction, and clustering were performed using Seurat. TCR and BCR immune repertoire analyses were performed using Immunarch. Results: SARS-CoV-2 convalescent patients with IBD had detectable but variable SARS-CoV-2 antibody levels (range 0-469 U/mL), whereas SARSCoV- 2 naïve IBD patients had no detectable antibodies. The mean SARS-CoV-2 antibody concentration among the three IBD patients with the highest and three patients with the lowest groups differed by more than 10-fold (206.0 vs 17.5 U/mL, P<0.001). PBMC singlecell immunophenotyping revealed decreased naïve CD4+ T cell and increased CD14+ monocyte and memory CD4+ T cell proportions in IBD patients in the low versus high SARSCoV- 2 antibody group. There were higher numbers of HLA-DQA1+ B cells and CD8 T cells and lower GPR183+ B cells and CD8 T cells in the high SARS-CoV-2 antibody group. There was a trend towards decreased TCR and BCR repertoire diversity in the low SARS-COV-2 antibody group. Finally, we identified immunoglobulin gene signatures (IGHV1-69D/IGLV3- 25, IGHV3-48, IGHV3-7/IGKV41/IGLV1-47, IGHV3-7/IGKV4-1, IGHV3-7/IGKV4-44) that were enriched only in the high SARS-CoV-2 antibody group. Conclusions: Single-cell immunophenotyping of PBMC from convalescent patients with IBD reveal differences in CD4+ T cell, CD14+ monocyte, and HLA-DQA1+ and GPR183+ B and CD8 T cell immunophenotypes, immune repertoire diversity, and immunoglobulin gene signatures in patients with high versus low SARS-CoV-2 antibody levels.(Figure Presented)Figure 1. SARS-COV-2 Antibodies in Convalescent Patients with IBD and Single-Cell Immunophenotypes. A) SARS-COV-2 antibody levels in COVID-19 convalescent versus SARS-CoV-2 naïve patients with IBD B) T-SNE plot of PBMC immunophenotypes in all convalescent patients with IBD C) Differences in proportion of single-cell PBMC immunophenotypes in high versus low SARS-COV-2 antibody patients D) Differences in HLA-DQA1 and GPR183 immunophenotypes in high versus low SARS-COV-2 antibody patients.
ABSTRACT
Introduction: SARS-CoV-2 is known to infect the gastrointestinal tract and COVID-19 may manifest with gastrointestinal symptoms. Studies regarding the risks factors for COVID-19 and the impact of the pandemic on healthcare utilization in patients with functional gastrointestinal disorders (FGID) are lacking. Methods: We performed a retrospective study of consecutive patients with FGID (irritable bowel syndrome, gastroparesis, functional dyspepsia) who tested positive for SARS-CoV-2 and compared to a randomly selected sample of FGID who tested negative. We used multivariate logistic regression to determine risk factors for SARS-CoV-2 infection. We also evaluated healthcare utilization by comparing health care visits (ED, inpatient, outpatient), medication prescriptions, abdominal CT scans, and endoscopy rate 6 month pre pandemic and 6 months after the start of the pandemic (using 3/15/20 as a cut-off point). Results: We identified and analyzed 2592 patients with FGID who underwent SARS-CoV-2 testing (83 positive COVID-19 cases). The total positivity rate was 3.9%. Inpatient admissions (0.36 vs 0.50, p<0.001), outpatient visits (4.78 vs 5.68, p<0.001), number of abdominal CT scans (0.18 vs 0.23, p=0.002), number of upper endoscopies (0.10 vs 0.19, p<0.001), and number of colonoscopies (0.04 vs 0.10, p<0.001) were higher during the 6 months after the start of the pandemic (compared to the 6 months before). Prescription rate for PPIs, H2 blockers, opioids, and anti-platelet agents were also higher during the pandemic (Table 1). Patients had higher rates of symptoms including abdominal pain, vomiting, diarrhea, constipation, and weight loss during the pandemic, as reported by ICD coding. Similar trends were seen when stratifying by FGID type, and by SARS-CoV-2 test positivity (but did not reach statistical significance in the SARS-CoV-2 positive group. Active smoking, cough, pneumonia, and diarrhea-predominant IBS were associated with increased risk of COVID-19 among patients with FGID, while alcohol use and functional dyspepsia decreased this risk (Table 2). Discussion: Health care utilization among patients with FGIDs increased significantly during the pandemic, independent of SARS-CoV-2 positivity. Increased psychosocial stress and increased utilization of telehealth visits may partially explain this trend. Our data suggest that smoking status, cough, pneumonia, and diarrhea-predominant IBS could independently determine the increased risk of COVID-19 among patients with FGID.(Table presented)(Table presented)