Project description:Inflammatory bowel disease (IBD) patients are generally at an increased risk for viral diseases. Viral infections of tissue affected by chronic IBD are insufficiently understood, especially in the context of flare-ups; while some studies have confidently shown aggravation of symptoms in large cohorts, others found no association. Although not considered at an increased risk of Coronavirus Disease 2019 (COVID-19), IBD patients suffer more frequent gastrointestinal symptoms during COVID-19 and a worse outcome has been associated with certain IBD medications and disease activity. For this reason, we generated intestinal epithelial organoids from ileum with Crohn’s disease (CD) and colon with ulcerative colitis (UC) together with healthy controls. Each group included five to six patients. Using RNA sequencing we showed that IBD organoids were not more susceptible to infection. The highest viral load two days after infection was in healthy ileum and is correlated to the expression of SARS-CoV-2 entry receptor ACE2 and proteases CTSL/B. Pathway analyses determined an apparently weaker defense reaction in CD organoids to SARS-CoV-2 which could simply be due to the lower viral load compared to the healthy group. In contrast to CD, there was an activation of viral defense in infected UC colon, especially interferon signaling, resembling highly infected healthy ileum. This was not seen in healthy colon and was unexpected since UC and healthy colon did not differ in viral load. In uninfected IBD organoids compared to healthy, there was an already stronger basal expression of genes implicated in viral defense, for example, of viral sensors OAS1 and OASL in CD and interferon regulatory transcription factor IRF7 in UC. Some were further influenced by SARS-CoV-2 infection with notable differences between CD and UC. To conclude, infection with SARS-CoV-2 did not lead to higher viral numbers in IBD organoids providing reassurance for patients in remission. Still, we observed a more pronounced epithelial defense reaction to the virus in UC colon, prompting further investigations on whether this could be the reason for stronger gastrointestinal symptoms of COVID-19 seen in IBD patients or if it could lead to a consequent IBD flare.
Project description:SARS-CoV2, severe acute respiratory syndrome coronavirus 2, is frequently associated with neurological manifestations. Despite the presence of mild to severe CNS-related symptoms in a cohort of patients, there is no consensus whether the virus can infect directly brain tissue or if the symptoms in patients are a consequence of peripheral infectivity of the virus. Here, we use a human stem cell-derived cortical organoid model to assess SARS-CoV2 infectivity of brain cells and unravel the cell-type tropism and its downstream pathological effects. Our results show consistent and reproducible low levels of SARS-CoV2 infection in human cortical organoids at different maturation stages in vitro. We found that astrocytes, deep projection neurons, upper callosal neurons and inhibitory neurons were infected by SARS-CoV2. Interestingly, astrocytes showed the highest infection rate among all infected cell populations that led to increased presence of reactive states. Further, transcriptomic analysis revealed overall changes in expression of genes related to oxidative phosphorylation, TNFA signaling, astrocyte activation and metabolic changes. Thus, local and minor infectivity of SARS-CoV2 in the brain may induce widespread adverse effects in brain cell populations.
Project description:This dataset looks at the transcriptome of in vitro-differentiated primary lung cells infected with SARS-CoV2. Some cells have been treated with the drug Enzalutamide.
Project description:RNA-Seq was carried out in order to obtain the time dependent expression dynamics of SARS-CoV2 (Trondheim strain)-induced transcriptome changes in human lung epithelial Calu-3 cells.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus diseases 2019 (COVID-19) and broncho-alveolar inflammation (Merad and Martin, 2020). IL-9 induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation (Temann et al., 1998). However, the role of IL-9 is not yet identified in SARS-CoV2 infection. Here we show that IL-9 promotes SARS-CoV2 infection and airway inflammation in K18-hACE2 transgenic (ACE2.Tg) mice, as IL-9 blockade reduces SARS-CoV2 infection and suppressed airway inflammation. Foxo1 is essential for the induction of IL-9 in helper T (Th) cells (Malik et al., 2017). While ACE2.Tg mice with Foxo1-deficiency in CD4+ T cells were performed to be resistant to SARS-CoV2 infection associated with reduced IL-9 production, exogenous IL-9 made Foxo1-deficient mice susceptible to SARS-CoV2 infection with increased airway inflammation. Collectively, we identify a mechanistic insight of IL-9-mediated regulation of antiviral and inflammatory pathways in SARS-CoV2 infection, and unravel a principle for the development of host-directed therapeutics to mitigate disease severity.
Project description:This dataset looks at the transcriptome of in vitro-differentiated primary lung cells during an infection time course of SARS-CoV2. Some cells have been treated with the drug Enzalutamide. Cells from one man and one female were mixed to minimize the technical variability, and can be separated by SNPs (SNPs not included, but the calculated cell-donor associations are provided).