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BackgroundMost studies on the safety and efficacy of antitumor necrosis factor alpha (anti-TNF) agents in the treatment of inflammatory bowel disease have included few Black patients.AimsWe aimed to evaluate the therapeutic response rate in Black IBD patients compared with White patients.MethodsWe conducted a retrospective review of IBD patients who were treated with anti-TNF agents and assessed those with therapeutic drug levels for clinical, endoscopic, and radiologic response to anti-TNF treatment.ResultsWe identified 118 patients who met the inclusion criteria. Black IBD patients had significantly higher prevalence of endoscopic and radiologic active disease compared with White patients (62% and 34%, respectively; P = .023), despite similar proportions reaching therapeutic titers (67% and 55%, respectively; P = .20). Moreover, Black patients had significantly higher rate of IBD-related hospitalizations than White patients (30% vs 13%, respectively; P = .025) while on anti-TNF agents.ConclusionsBlack IBD patients on anti-TNF agents had a significantly higher prevalence of active disease and more IBD-related hospitalizations than White patients.

Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection ofCandidaspecies-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals, including confirmatory diagnostic testing demonstrating elevated serum (1, 3)-β-D-glucan and/or confirmed fungal culture of the predicted pathogen. Using matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, we identify epithelial immune signatures suggestive of IL-17 stimulation and anti-fungal immunity. Further, we observe significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggests that IL-17 stimulation – in part driven byCandidacolonization – and blunted type I/III interferon signaling represents a common feature of severe COVID-19 infection.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which presents with respiratory symptoms including fever, sore throat, cough and congestion, suggesting that infection of the oral cavity and nasopharynx (ONP) is an obligate step in its pathogenesis Consistent with this role in the initial infection, oral and nasopharyngeal epithelial cells express the SARS-CoV-2 spike protein receptor, angiotensin-converting enzyme 2 (ACE2) (1), and RT-PCR based testing can routinely detect SARS-CoV-2 RNA within both the nasal and buccal tissues Local innate and adaptive immune responses in the oral epithelia are almost certainly involved in the defense against SARS-CoV-2 infection, yet little is known about these defenses

IntroductionThe COVID-19 pandemic has had a tremendous negative effect on the mental health and well-being of Canadians. These mental health challenges are especially acute among vulnerable Canadian populations. People living in Canada’s most populous province, Ontario, have spent prolonged time in lockdown and under public health measures and there is a gap in our understanding of how this has impacted the mental health system. This protocol describes the Mental health and Addictions Service and Care Study that will use a repeated cross-sectional design to examine the effects, impacts, and needs of Ontario adults during the COVID-19 pandemic.Methods and analysisA cross-sectional survey of Ontario adults 18 years or older, representative of the provincial population based on age, gender and location was conducted using Delvinia’s AskingCanadians panel from January to March 2022. Study sample was 2500 in phases 1 and 2, and 5000 in phase 3. The Alcohol, Smoking and Substance Involvement Screening Test and Diagnostic Statistical Manual-5 Self-Rated Level 1 Cross-Cutting Symptom Measure-Adult were used to assess for substance and mental health concerns. Participants were asked about mental health and addiction service-seeking and/or accessing prior to and during the pandemic. Analyses to be conducted include: predictors of service access (ie, sociodemographics, mental illness and/or addiction, and social supports) before and during the pandemic, and χ2tests and logistic regressions to analyse for significant associations between variables and within subgroups.Ethics and disseminationEthics approval was obtained from the Sunnybrook Research Ethics Board. Dissemination plans include scientific publications and conferences, and online products for stakeholders and the general public.

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.

SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ “hillock”-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19., Graphical abstract, A study of nasopharyngeal swabs from healthy and COVID-19-infected individuals shows how infection leads to compositional changes in the respiratory epithelium, with early dampened antiviral responses in the nasal epithelia likely underlying and preceding severe disease.

Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated respiratory co-infection among people with severe COVID-19, however the frequency and clinical impact is currently unknown. We have previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity with the local behavior of nasal epithelial and immune cells. In agreement with other human cohorts, this prior study suggested that a deficiency in host immunity, particularly in type I/ III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. Here, we have performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent nasal and/or endotracheal infection with Candida spp. We present the clinical characteristics of these individuals, including confirmatory testing demonstrating elevated serum (1,3)-β-D-glucan and/or a positive fungal culture. Finally, using the matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, in addition to blunted type I/III interferon signaling previously reported, we identified epithelial and mucosal immune signatures consistent with augmented IL-17 responses, suggestive of activated anti-fungal immunity. These results indicate that a subset of patients with severe COVID-19 exhibit increased frequency of concurrent fungal infections associated with augmented IL-17 responses and suggest that concurrent fungal infection may be contributing to SARS-C0V-2 mediated inflammatory pathology. This project has been made possible in part by grant number 2020-216949 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation to Alex K. Shalek and Jose Ordovas-Montanes. Carly G. K. Ziegler was supported by T32GM007753 from the NIH. Jose Ordovas-Montanes is a New York Stem Cell Foundation – Robertson Investigator. Jose Ordovas-Montanes was supported by the Richard and Susan Smith Family Foundation, the AGA Research Foundation’s AGA-Takeda Pharmaceuticals Research Scholar Award in IBD – AGA2020-13-01, the Food Allergy Science Initiative, and The New York Stem Cell Foundation. Bruce H. Horwitz was supported by DK122532-01A1, NIH; 12019PG-CD002, The Leona M. and Harry B. Helmsley Charitable Trust; SRA #54518, and Crohn’s and Colitis Foundation. P.L. was supported by 5T32AG000222 from the NIH. Andrew W. Navia was supported by the Ludwig Center for Molecular Oncology at MIT. Alex K. Shalek was supported by the Bill and Melinda Gates Foundation, Sloan Fellowship in Chemistry, the NIH (5U24AI118672), and the Ragon Institute of MGH, MIT and Harvard.

A protocol for recovering viable single cell suspensions from cryopreserved human nasopharyngeal swabs for downstream applications, such as single-cell RNA-seq. The illustrated schematic below details the process.