RESUMO
During the SARS-CoV-2 pandemic, the Dr. Risch medical group employed the multiplex TaqPathTM COVID-19 CE-IVD RT-PCR Kit for large-scale routine diagnostic testing in Switzerland and the principality of Liechtenstein. The TaqPath Kit is a widely used multiplex assay targeting three genes (i.e., ORF1AB, N, S). With emergence of the B.1.1.7 (Alpha) variant, a diagnostic flaw became apparent as the amplification of the S-gene target was absent in these samples due to a deletion (ΔH69/V70) in the Alpha variant genome. This S-gene target failure (SGTF) was the earliest indication of a new variant emerging and was also observed in subsequent variants such as Omicron BA.1 and BA4/BA.5. The Delta variant and Omicron BA.2 did not present with SGTF. From September 2020 to November 2022, we investigated the applicability of the SGTF as a surrogate marker for emerging variants such as B.1.1.7, B.1.617.2 (Delta), and Omicron BA.1, BA.2, and BA.4/BA.5 in samples with cycle threshold (Ct) values < 30. Next to true SGTF-positive and SGTF-negative samples, there were also samples presenting with delayed-type S-gene amplification (higher Ct value for S-gene than ORF1ab gene). Among these, a difference of 3.8 Ct values between the S- and ORF1ab genes was found to best distinguish between "true" SGTF and the cycle threshold variability of the assay. Samples above the cutoff were subsequently termed partial SGTF (pSGTF). Variant confirmation was performed by whole-genome sequencing (Oxford Nanopore Technology, Oxford, UK) or mutation-specific PCR (TIB MOLBIOL). In total, 17,724 (7.4%) samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% [92.7%, 93.7%] and 99.3% [99.2%, 99.5%], respectively. Sensitivity was increased to 98.2% [97.9% to 98.4%] and specificity lowered to 98.9% [98.6% to 99.1%] when samples with pSGTF were included. Furthermore, weekly logistic growth rates (α) and sigmoid's midpoint (t0) were calculated based on SGTF data and did not significantly differ from calculations based on comprehensive data from GISAID. The SGTF therefore allowed for a valid real-time estimate for the introduction of all dominant variants in Switzerland and Liechtenstein.
RESUMO
BACKGROUND: Data on the cardiovascular risk associated with the adipose-tissue-related hormone resistin are scarce. METHODS: We measured serum resistin and established vascular risk factors in 547 consecutive patients (age 63+/-10 years) undergoing coronary angiography for the evaluation of stable coronary artery disease. Prospectively, we recorded major coronary events and cumulative vascular events over 4 years. RESULTS: 60% of our patients had significant coronary stenoses with a lumen narrowing > or =50%. Serum resistin was moderately but significantly correlated with age (r=0.139; p=0.001), high-sensitivity C-reactive protein (hsCRP; r=0.228; p<0.001) and decreasing renal function (r=0.240; p<0.001). However, there was no significant difference of serum resistin between patients with CAD and those in whom angiography did not show CAD (4.5 [3.1-5.8] vs. 4.3 [3.4-5.3] ng/ml; p=0.545) and between patients with > or =50% coronary narrowings and those without such lesions (4.5 [3.2-5.9] vs. 4.3 [3.1-5.5] ng/ml; p=0.265). Prospectively, Cox regression analyses neither indicated an association between serum resistin and major coronary events nor between serum resistin and cumulative vascular events. CONCLUSIONS: Among coronary patients serum resistin is significantly correlated with hsCRP, age and decreasing renal function but resistin is neither associated with the presence of significant coronary stenoses nor with the incidence of future vascular events.