Reduced SARS-CoV-2 infection and altered antiviral transcriptional response in IBD intestinal organoids. (preprint)

IBD is characterized by altered immune reactions and infections are thought to trigger the chronic inflammatory response in IBD. The gut represents a productive reservoir for SARS-CoV-2 and the aforementioned factors together with immunosuppression used to treat IBD are likely influencing the outcomes of IBD patients in COVID-19. We used large and small intestinal organoids from IBD patients and controls to comparatively assess the transcriptional response of the gut epithelium during SARS-CoV-2 infection. Our analysis showed that IBD epithelia exhibit reduced viral loads compared to controls associated with a reduced expression of SARS-CoV-2 entry factors including the host receptor ACE2. Moreover, several genes implicated in the epithelial response to viral infection are intrinsically altered in IBD likely counteracting viral propagation. Notably, differences between IBD phenotypes exist wherein ulcerative colitis represents with induced cell death pathways and an induction of IL-1{beta} despite overall lower viral loads suggestive of increased epithelial stress in this IBD phenotype. Altogether our analysis shows that IBD epithelia are not more prone to SARS-CoV-2 infection but epithelia from ulcerative colitis and Crohn's disease exhibit specific differences which might explain the differing COVID-19 outcomes between IBD phenotypes.

B and T Cell Response to SARS-CoV-2 Vaccination in Health Care Professionals With and Without Previous COVID-19 (preprint)

Background: In recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies.Methods: In a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon g release assays and intracellular flow cytometry. Vaccine-related side effects were captured. Findings: Prior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein.Interpretation: Herein, we corroborate recent findings suggesting that in convalescents a single vaccine dose may be sufficient to boost adequate protection against SARS-CoV-2. New spike mutated virus variants render the highly conserved nucleocapsid protein – eliciting strong SARS-CoV-2 specific T cell immunity – an interesting additional vaccine target.Funding: Christian Doppler Research Association, Johannes Kepler University LinzDeclaration of Interests: TRK and MF are employees of Baxter AG, Vienna, Austria, now part of the Takeda group of companies and have Takeda stock interest. All other authors declare no competing interests.Ethics Approval Statement: This study was approved by the ethics committee of the Johannes Kepler University Linz (EC-No. 1322/2020) and informed consent was obtained from all study subjects.