Seroconversion following SARS-CoV-2 Infection or Vaccination in Pediatric IBD Patients (preprint)

Objective: Inflammatory bowel disease (IBD) patients are commonly treated with immunomodulatory medications, and the effect of these medications on seroconversion to SARS-CoV-2 infection and vaccination are scant, particularly in pediatrics. We sought to determine serologic responses to SARS-CoV-2 infection and vaccination in pediatric IBD patients. Design: We conducted a single-center, retrospective study of all pediatric ([≤]21 years old) IBD patients in whom a SARS-CoV-2 IgG Antibody Assay was performed between April 2020 and May 2021 at our tertiary care center. This assay measures IgG antibody to the full-length SARS-CoV-2 spike protein and was routinely collected at infusion and outpatient clinic visits. The primary outcome was SARS-CoV-2 seroconversion, and the secondary outcome was titer level, with high titer defined as [≥]960 titer or >40 AU/mL. Clinical characteristics, including demographics, IBD location, behavior, activity, and therapy, SARS-CoV-2 exposures, COVID-19 testing and symptoms, SARS-CoV-2 infection status (WHO COVID-19: Case Definitions, 2020) and COVID-19 vaccination status and type, were gathered, and univariate analyses examined associations between clinical characteristics and outcome measures. Results: There were 340 pediatric patients with SARS-CoV-2 Antibody Testing; 15% for confirmed or probable COVID-19, 2% for suspected COVID-19, 16% for asymptomatic exposure to a close contact with SARS-CoV-2 infection, 61% without any prior symptoms or exposures, and 6% for history of COVID-19 vaccination. Patients with confirmed or probable COVID-19 infection had a 90% rate of seroconversion, with 76% of these patients on biologic therapy. Patients post-infection without seroconversion had a significantly longer interval between infection and antibody assay (P=0.03). Within those with asymptomatic SARS-CoV-2 exposure, 43% had seroconversion, and there were no identified clinical characteristics associated with positive titer. All pediatric patients who received vaccination seroconverted, and all who received mRNA vaccinations, including one after a single dose, achieved high titer levels; 100% of those who received vaccination were on biologic or small molecule therapy, including one on combination therapy with ustekinumab and tofacitinib. Conclusion: Pediatric IBD patients have strong serologic antibody responses to SARS-CoV-2 infection and COVID-19 vaccination despite high rates of immunomodulatory therapy.

SARS-CoV-2-specific IgA and limited inflammatory cytokines are present in the stool of select patients with acute COVID-19 (preprint)

Background and aims: Immune dysregulation caused by SARS-CoV-2 infection is thought to play a pathogenic role in COVID-19. SARS-CoV-2 can infect a variety of host cells, including intestinal epithelial cells. We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. Methods: We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool and serum samples from a prospectively enrolled cohort of 44 hospitalized COVID-19 patients. Results: SARS-CoV-2 RNA was detected in stool of 41% of patients and was found more frequently in patients with diarrhea than those without (16[44%] vs 5[19%], p=0.06). Patients who survived had lower median viral genome copies than those who did not (p=0.021). Compared to uninfected controls, COVID-19 patients had higher median fecal levels of IL-8 (166.5 vs 286.5 pg/mg; p=0.05) and lower levels of fecal IL-10 (678 vs 194 pg/mg; p<0.001) compared to uninfected controls. Stool IL-23 was higher in patients with more severe COVID-19 disease (223.8 vs 86.6 pg/mg; p=0.03) and we find evidence of intestinal virus-specific IgA responses, which was associated with more severe disease. Fecal cytokines and calprotectin levels were not correlated with gastrointestinal symptoms or with the level of virus detected. Conclusions: Although SARS-CoV-2 RNA was detectable in the stools of COVID-19 patients and select individuals had evidence for a specific mucosal IgA response, intestinal inflammation was limited, even in patients presenting with gastrointestinal symptoms.

Vapur: A Search Engine to Find Related Protein - Compound Pairs in COVID-19 Literature (preprint)

Coronavirus Disease of 2019 (COVID-19) created dire consequences globally and triggered an enormous scientific effort from different domains. Resulting publications formed a gigantic domain-specific collection of text in which finding studies on a biomolecule of interest is quite challenging for general purpose search engines due to terminology-rich characteristics of the publications. Here, we present Vapur, an online COVID-19 search engine specifically designed for finding related protein - chemical pairs. Vapur is empowered with a biochemically related entities-oriented inverted index in order to group studies relevant to a biomolecule with respect to its related entities. The inverted index of Vapur is automatically created with a BioNLP pipeline and integrated with an online user interface. The online interface is designed for the smooth traversal of the current literature and is publicly available at https://tabilab.cmpe.boun.edu.tr/vapur/.

Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease (preprint)

Immune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation. We have observed that IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines. Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork between COVID-19 and IBD. These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19.