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1.
Gastroenterology ; 162(7):S-291-S-292, 2022.
Article in English | EMBASE | ID: covidwho-1967287

ABSTRACT

Background: Post-COVID-19 conditions are defined as new, recurring, or ongoing health issues which present weeks after SARS-CoV-2 infection. The gastrointestinal (GI) involvement of COVID-19 suggests that a group of patients with lingering GI symptoms may develop Post-COVID-19 DGBI including irritable bowel syndrome (IBS) (Schmulson M et al. Am J Gastroenterol. 2021;116:4-7). In this study, we aimed to determine the epidemiological features of Post-COVID-19 DGBI. Methods: Subjects with confirmed COVID-19 at least 6 months before the study who had sustained GI symptoms were invited to complete an internet-based survey on Qualtrics, between March and August 2021. The survey included demographics, acute symptoms, comorbidities, as well as Rome IV questionnaire, Generalized Anxiety Disorder questionnaire (GAD-7) and Patient Health Questionnaire (PHQ)-9 for depression. Data was analyzed using ANOVA and multivariate analysis. Findings were reported as percentage or [p-value;(95% odds ratio CI)]. Results: Overall, 164 subjects (70% female, 14% male, and others unknown) with a positive COVID-19 test completed the survey. Among them, 4% were >65 years old and 24% reported hospitalization. Body mass index ³30 was present in 38%, diabetes in 6.7%, and vitamin D deficiency in 11% of the participants. In total, 108 (66%) subjects fulfilled Rome IV criteria for at least one DGBI. Of 108 with DGBI, only 27 (25%) had DGBI before COVID-19;DGBI developed in 81 subjects after COVID-19. The most common Post-COVID-19 DGBI were functional dyspepsia observed in 38 (postprandial distress syndrome n=31, epigastric pain syndrome n=22) followed by IBS in 26 subjects (IBS with Diarrhea n=7, IBS with Constipation n=4, Mixed-IBS n=14, Unsubtyped IBS n=1) (Table-1). The risk factors of severe COVID-19 including age >65, diabetes, and obesity were not associated with developing Post-COVID- 19 DGBI. Seventy (86%) of subjects with Post-COVID-19 DGBI had at least one GI symptom (abdominal pain, nausea/vomiting, and/or diarrhea) in the acute phase of COVID-19. Nausea/ vomiting during the acute illness increased [p-value of 0.02 with 95% OR CI (0.7-10.4)], and BMI less than 25 also increased the odds [p-value of 0.03 (95% OR CI: 0.26-8.4)] for Post-COVID-19 IBS. Anxiety was present in 48% and depression in 65% of subjects with Post-COVID-19 DGBI. Conclusions: Post-COVID-19 DGBI are new entities associated with a high rate of anxiety and depression. Although the majority of those with Post-COVID-19 DGBI reported having GI symptoms in the acute illness, some appeared in subjects without acute GI symptoms. (Table Presented)

2.
Gastroenterology ; 162(7):S-247, 2022.
Article in English | EMBASE | ID: covidwho-1967258

ABSTRACT

Background: Gastric muscularis propria immune cells play an instrumental role in homeostasis and disease. A subset of these cells, muscularis macrophages (MMs) are involved in the pathobiology of diabetic gastroparesis (DG) but are poorly understood. This study aims to survey transcriptional and functional profiling of gastric MMs in DG and diabetes. Methods: Full-thickness gastric body biopsies were obtained from patients with DG and diabetic controls. CD45+ cells were isolated from dissociated muscle tissue using magnetic beads. 10xGenomics was used for scRNA-seq library prep and cells sequenced by Illumina HiSeq4000. Bioinformatic analyses was performed using Suite and Seurat. Myeloid cells were annotated through a pseudogating strategy that identifies cells by differential expression levels of HLA-DR, CD14, CD11b, and CD11c based on flow cytometry-based gating utilized in a recent analysis of human small intestinal MMs. Canonical signaling pathways were determined using Ingenuity Pathway Analysis (IPA). Results: A total of 21,740 high-quality single-cell transcriptomes were generated from 16 subjects (DG=6, age 32±8 yr, BMI 23.7±3.9, 48.2±40.1% 4 hr gastric retention, average GCSI score 3.7±0.5;Diabetic controls= 10, age 53±13 yr, BMI 42.2±5.7). Through annotating 8,693 myeloid cells (DG 1509, Controls 7184), we characterized 1,788 as MMs (CD45+HLA-DR+) and 448 as dendritic cells (CD14-CD11c+). Utilizing a priori markers for pseudogating, the MMs were divided into four populations (Figure 1): subset 1 (CD14+CD11c+HLA-DRint, 5.6%), subset 2 (CD14+CD11c+HLA-DRhi, 36.0%), subset 3 (CD14+CD11c-CD11b-, 41.8%), and subset 4 (CD14+CD11c-CD11b+, 16.6%). The overall proportions of cells in the 4 subsets were similar to a prior approach in small bowel using gating. The expected ratio of cells from DG/diabetic control was 21% based on imputed cells. Subsets 1 and 4 were significantly decreased in DG compared to controls with ratios 15% and 14% respectively while subsets 2 and 3 were unchanged (21% and 20%). On IPA, phagosome formation and immune cell trafficking represented canonical signaling pathways of subset 1 and coronavirus phagocytosis pathway and phagosome formation of subset 4. Canonical genes of subset 1 included S100A12, A8, A9, and CSTA and subset 4 as LYVE1, MAF, MRC1 (CD206), MS4A4, and A2M. Subset 4 also had the highest expression of neuron-related genes (NPTX2, BMP2) similar to that observed in the small intestine. Conclusions: Pseudogating based on the transcriptomic expression of gastric immune cells reveal MM clusters similar in gene expression and proportions to previously characterized MMs in human small bowel using gating. The reduction of MM clusters associated with anti-inflammatory, phagocytosis, and neuronal signaling in specialized MMs subsets may suggest candidate targets in the pathophysiology of DG. Supported by NIHDK074008. (Figure Presented) Figure 1. Single-Cell RNA-Seq Profiling of Human Gastric Muscularis Macrophages in DG and Diabetes. T-distributed Stochastic Neighbor Embedding (tSNE) plot of muscularis macrophages in DG and diabetic control subjects by their differential genes from MAST (FDR < 0.05), color-coded by Status. *Mf1 and Mf2 not visualized as distinct clusters due to inadequate separation of overall gene expression in cells distinguished by HLA-DRint (Mf1) and HLA-DRhi (Mf2)

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