Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Determinants of sudden cardiac death in patients with persistent atrial fibrillation in the rate control versus electrical cardioversion (RACE) study

This report evaluated the correlates of sudden cardiac and nonsudden cardiac death in patients with persistent atrial fibrillation randomized to rate or rhythm control in the RAte Control vs Electrical cardioversion (RACE) study. Sudden cardiac death was observed in 16 patients, 8 patients in each group. Previous myocardial infarction resulted in a 4.9-fold increased risk of sudden death (95% confidence interval 1.8 to 13.2). The use of beta blockers showed their protective nature (hazard ratio 0.2, 95% confidence interval 0.05 to 0.9). The randomized treatment strategy, heart rhythm during follow-up, use of antiarrhythmic drugs, and number of stroke risk factors were not associated with sudden cardiac death. In conclusion, the treatment of underlying disease, rather than the heart rhythm, seems essential to prevent mortality

Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies

Aims The AFFIRM and RACE studies showed that rate control is an acceptable treatment strategy for atrial, fibrillation (AF). We examined whether strict rate control offers benefit over more lenient rate control. Methods and Results We compared the outcome of patients enrolled in the rate-control arms of AFFIRM and RACE, using data from patients who met a composite of overlapping inclusion and exclusion criteria. We evaluated 1091 patients, 874 from AFFIRM and 217 from RACE. In AFFIRM, the rate-control strategy aimed for a resting heart rate = 100 (hazard ratios 0.69 and 0.58, respectively, for = 100 bpm). Conclusion Stringency of the approach to rate control, based on the comparison of the AFFIRM and RACE studies, was not associated with an important difference in clinical events

Gender-related differences in rhythm control treatment in persistent atrial fibrillation:data of the Rate Control Versus Electrical Cardioversion (RACE) study

ObjectivesThis study sought to compare whether gender affects the outcome of rate versus rhythm control treatment in patients with persistent atrial fibrillation (AF).BackgroundLarge trials have shown that rate control is an acceptable alternative to rhythm control. However, the effects of treatment may differ between male and female patients.MethodsIn the Rate Control versus Electrical Cardioversion (RACE) study, 522 patients (192 female) were included and randomized to rate or rhythm control. The occurrence of cardiovascular end points and quality of life (QoL) were compared between female and male patients.ResultsAt baseline, female patients differed from male patients with regard to age, underlying heart disease, diabetes mellitus, and left ventricular function. Female patients had more AF-related complaints, and QoL was significantly lower. After a mean follow-up of 2.3 ± 0.6 years, cardiovascular morbidity and mortality was equally distributed between female (21%) and male patients (19%). However, in contrast to male patients, female patients randomized to rhythm control developed more end points (adjusted hazard ratio was 3.1 [95% confidence interval 1.5 to 6.3], p = 0.002), mainly heart failure, thromboembolic complications, and adverse effects of antiarrhythmic drugs, compared with rate control randomized female patients. During follow-up, QoL in female patients remained worse compared with that for male patients. Randomized strategy did not influence QoL in female patients.ConclusionsIn female patients with persistent AF, a rhythm control approach leads to more cardiovascular morbidity and mortality. Because treatment strategy did not influence QoL in female patients, a rate control approach may be considered in these patients