Does Atrial Fibrillation at Diagnosis Change Prognosis in Patients with Aortic Stenosis?

Background: Aortic stenosis (AS) is a common valve disease and atrial fibrillation (AF) is the most common cardiac arrhythmia, frequently associated with AS. This study aimed to evaluate the impact of AF on mortality in patients with moderate and severe AS. Methods: We retrospectively analyzed 1070 consecutive moderate and severe AS patients (57% were male, age was 69 ± 10, severe AS 22.5%), who underwent transthoracic echocardiography from March 2018 to November 2021. AS severity was defined by specific threshold values with severe AS being defined by a peak velocity > 4 m/s, an MPG > 40 mmHg, and an AVA < 1 cm2 and moderated by a peak velocity of 3-4 m/s, an MPG 20-40 mmHg and an AVA 1-1.5 cm. Patients with AF were defined as those having a history of AF when AS was found on the index echocardiography. The follow-up assessment in December 2023 ascertained vital status and data on aortic valve replacement (AVR). Results: 790 (73.8%) patients were with sinus rhythm (SR) and 280 (26.2%) patients with AF. Mortality was higher in patients with AF than in those with SR (46% vs. 36.2% HR 1.424, 95% CI 1.121-1.809, p = 0.004). After adjusting for clinical confounders, mortality risk in AF relative to SR remained significant (HR 1.284, 95% CI 1.03-1.643, p = 0.047). Patients with AF demonstrated high mortality risk in the moderate aortic stenosis stratum (HR 1.376, 95% CI 1.059-1.788, p = 0.017), with even greater risk in the severe AS stratum (HR 1.644, 95% CI 1.038-2.603, p = 0.034) with significant interaction (p = 0.007). In patients with AF AVR demonstrated a protective effect on survival (HR 0.365, 95% CI 0.202-0.627, p < 0.001), but to a lesser degree than in patients with sinus rhythm (HR 0.376, 95% CI 0.250-0.561, p < 0.001) without significant interaction (p = 0.278). In patients with AF mortality risk was high in the conservative treatment stratum (HR 1.361, 95% CI 1.066-1.739, p = 0.014), in the AVR stratum mortality risk was higher but did not reach statistical significance (HR 1.823, 95% CI 0.973-3.414, p = 0.061). However, when corrected for echocardiographic variables strongly correlated with AF, AF was no longer independently associated with all-cause mortality. (HR 0.97 95% CI 0.709-1.323, p = 0.84). Conclusions: Patients with moderate and severe AS and AF have worse prognosis than patients with SR which can be explained by cardiac damage. AVR improves survival in patients with AF and with SR.

Long-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity.

Under-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful.

A Dried Blood Spot protocol for high-throughput quantitative analysis of SARS-CoV-2 RBD serology based on the Roche Elecsys system.

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples (n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns.