Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.
Transcatheter aortic valve implantation (TAVI), now a common procedure to treat high-risk patients with severe aortic stenosis, has rapidly been expanding into younger and lower-risk populations, creating a need to better understand long-term outcome after TAVI. The aim of the present investigation was to determine the incidence, risk factors for, clinical presentation of, and outcome after prosthetic valve endocarditis (PVE) in patients treated with TAVI in a nationwide study. Three registries were used: a national TAVI registry, a national diagnosis registry, and a national infective endocarditis registry. Combining these registries made it possible to perform a nationwide, all-comers study with independent and validated reporting of PVE in 4336 patients between 2008 and mid-2018. The risk for PVE after TAVI was 1.4% (95% confidence interval 1.0–1.8%) the first year and 0.8% (0.6–1.1%) per year thereafter. One-year survival after PVE diagnosis was 58% (49–68%), and 5-year survival was 29% (17–41%). Body surface area, estimated glomerular filtration rate <30 mL/min/1.73 m2, critical pre-operative state, mean pre-procedural valve gradient, amount of contrast dye used, transapical access, and atrial fibrillation were identified as independent risk factors for PVE. Staphylococcus aureus was more common in early (<1 year) PVE. Infection with S. aureus, root abscess, late PVE, and non-community acquisition was associated with higher 6-month mortality. The incidence of PVE was similar to that of surgical bioprostheses. Compromised renal function was a strong risk factor for developing PVE. In the context of PVE, TAVI seems to be a safe option for patients. NCT03768180 (http://clinicaltrials.gov/).
We compared the risk of severe COVID-19 during two periods 2021 and 2022 when Delta and Omicron, respectively, were the dominating virus variants in Scania county, Sweden. We adjusted for differences in sex, age, comorbidities, prior infection and vaccination. Risk of severe disease from Omicron was markedly lower among vaccinated cases. It was also lower among the unvaccinated but remained high (> 5%) for older people and middle-aged men with two or more comorbidities. Efforts to increase vaccination uptake should continue.