ABSTRACT
INTRO: Viruses, including SARS-CoV-2, which causes COVID-19, are constantly changing. These genetic changes (aka mutations) occur over time and can lead to the emergence of new variants that may have different characteristics. After the first SARS-CoV-2 genome was published in early 2020, scientists all over the world soon realized the immediate need to obtain as much genetic information from as many strains as possible. However, understanding the functional significance of the mutations harbored by a variant is important to assess its impact on transmissibility, disease severity, immune escape, and the effectiveness of vaccines and therapeutics. METHODS: Here in Canada, we have developed an interactive framework for visualizing and reporting mutations in SARS-CoV-2 variants. This framework is composed of three stand-alone yet connected components;an interactive visualization (COVID-MVP), a manually curated functional annotation database (pokay), and a genomic analysis workflow (nf-ncov-voc). Findings: COVID-MVP provides (i) an interactive heatmap to visualize and compare mutations in SARS-CoV-2 lineages classified across different VOCs, VOIs, and VUMs;(ii) mutation profiles including the type, impact, and contextual information;(iii) annotation of biological impacts for mutations where functional data is available in the literature;(iv) summarized information for each variant and/or lineage in the form of a surveillance report;and (v) the ability to upload raw genomic sequence(s) for rapid processing and annotating for real-time classification. DISCUSSION: This comprehensive comparison allows microbiologists and public health practitioners to better predict how the mutations in emerging variants will impact factors such as infection severity, vaccine resistance, hospitalization rates, etc. CONCLUSION: This framework is cloud-compatible & standalone, which makes it easier to integrate into other genomic surveillance tools as well. COVID-MVP is integrated into the Canadian VirusSeq data portal (https://virusseqdataportal.ca) - a national data hub for SARS-COV-2 genomic data. COVID-MVP is also used by the CanCOGeN and CoVaRR networks in national COVID-19 genomic surveillance.
ABSTRACT
Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. IBD patients were underrepresented in SARS-CoV- 2 mRNA vaccine trials. Case reports indicated that adverse events post-vaccination, including IBD flare, were more common among children, and those with prior COVID-19. Aim(s): To find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV- 2 mRNA vaccination. Method(s): In this observational case-control study, 37 children with IBD (CD:16, UC: 21) aged 12-18 years and 55 healthy age-matched children were enrolled. Blood was collected before and 2-4 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine dose. Whole blood count, fibrinogen, inflammatory markers (CRP, ferritin), anti-SARS- CoV- 2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Lag time, endogen thrombin potential (ETP), peak thrombin, time-to- peak were calculated. Detailed clinical parameters including post-vaccination symptoms, COVID-19 history, disease activity scores (PUCAI, Mayo score, PCDAI) were registered. Result(s): CRP was significantly elevated in children with IBD and showed a positive correlation with ETP (CD: R = 0.700;p = 0.003 and CU: R = 0.501;p = 0.020). TG parameters did not differ between patients and controls pre-or post-vaccination. TG parameters remained unaltered post-vaccination in both groups. IBD disease flare was not observed post-vaccination, but reduced anti-SARS- CoV- 2 antibody titers were found in 4 patients receiving immunosuppressive therapies. Previous COVID-19 infection had no effect on TG levels. Conclusion(s): Although TG parameters correlated with the level of inflammation in children with IBD, the extent of TG was not significantly different from healthy controls. TG parameters and IBD disease activity scores did not increase significantly following mRNA vaccination. Our results support the safety of SARS-CoV- 2 mRNA vaccination in children with IBD, highlighting observations of lower antibody titers in immunosuppressed children.