Reliability of a 2-Bout exercise test on a Wattbike cycle ergometer

Purpose: To determine the intraday and interday reliability of a 2 × 4-min performance test on a cycle ergometer (Wattbike) separated by 30 min of passive recovery (2 × 4MMP). Methods: Twelve highly trained cyclists (mean ± SD; age = 20 ± 2 y, predicted VO2max = 59.0 ± 3.6 mL · kg–1 · min–1) completed six 2 × 4MMP cycling tests on a Wattbike ergometer separated by 7 d. Mean power was measured to determine intraday (test 1 [T1] to test 2 [T2]) and interday reliability (weeks 1–6) over the repeated trials. Results: The mean intraday reliabilities of the 2 × 4MMP test, as expressed by the typical error of measurement (TEM, W) and coefficient of variation (CV, %) over the 6 wk, were 10.0 W (95% confidence limits [CL] 8.2–11.8), and 2.6% (95%CL 2.1–3.1), respectively. The mean interday reliability TEM and CV for T1 over the 6 wk were 10.4 W (95%CL 8.7–13.3) and 2.7% (95%CL 2.3–3.5), respectively, and 11.7 W (95%CL 9.8–15.1) and 3.0% (95%CL 2.5–3.9) for T2. Conclusion: The testing protocol performed on a Wattbike cycle ergometer in the current study is reproducible in highly trained cyclists. The high intraday and interday reliability make it a reliable method for monitoring cycling performance and for investigating factors that affect performance in cycling events

Reliability and Accuracy of Six Hand-Held Blood Lactate Analysers

The reliability and accuracy of five portable blood lactate (BLa) analysers (Lactate Pro, Lactate Pro2, Lactate Scout+, Xpress™, and Edge) and one handheld point-of-care analyser (i-STAT) were compared to a criterion (Radiometer ABL90). Two devices of each brand of analyser were assessed using 22 x 6 mL blood samples taken from five subjects at rest and during exercise who generated lactate ranging ~1-23 mM. Each sample was measured simultaneously ~6 times on each device. Reliability was assessed as the within-sample standard deviation (wsSD) of the six replicates; accuracy as the bias compared with the ABL90; and overall error (the root mean squared error (√MSE)) was calculated as the square root of (wsSD2 and bias2). The √MSE indicated that both the Edge and Xpress had low total error (~0-2 mM) for lactate concentrations 15 mM. In all cases, bias (negative) was the major contribution to the √MSE. In conclusion, in a clinical setting where BLa is generally <15 mM the Edge and Xpress devices are relevant, but for athlete testing where peak BLa is important for training prescription the Edge and Lactate Pro2 are preferred

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old