Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Renal Sympathetic Denervation Using an Irrigated Radiofrequency Ablation Catheter for the Management of Drug-Resistant Hypertension

ObjectivesThis study sought to assess whether renal sympathetic denervation (RSDN) can be achieved using an off-the-shelf saline-irrigated radiofrequency ablation (RFA) catheter typically employed for cardiac tissue ablation.BackgroundRSDN using a specialized solid-tip RFA catheter has recently been demonstrated to safely reduce systemic blood pressure in patients with refractory hypertension. For cardiac tissue ablation, RFA technology has evolved from nonirrigated to saline-irrigated ablation electrodes to improve both safety and effectiveness.MethodsTen patients with resistant hypertension underwent renal angiography, followed by bilateral RSDN with a saline-irrigated RFA catheter. Ambulatory blood pressure recordings (24 h) were obtained at baseline, 1, 3, and 6 months after the procedure. Repeat renal angiography was performed during follow-up to assess for arterial stenosis or aneurysm. In 5 patients, pre- and post-procedural serum measures of renal function and sympathetic activity were obtained: aldosterone; metanephrine; normetanephrine; plasma renin activity; and creatinine.ResultsOver a 6-month period: 1) the systolic/diastolic blood pressure decreased by −21/−11 mm Hg; 2) all patients experienced a decrease in systolic blood pressure of at least 10 mm Hg (range 10 to 40 mm Hg); 3) there was no evidence of renal artery stenosis or aneurysm at repeat angiography; and 4) there was a significant decrease in metanephrine (−12 ± 4, p = 0.003), normetanephrine (−18 ± 4, p = 0.0008), and aldosterone levels (−60 ± 33 ng/l, p = 0.02) at 3 months. There was no significant change in plasma renin activity (−0.2 mg/l/hod, p = 0.4). There was no significant change in serum creatinine (−1 mmol/l, p = 0.4).ConclusionsThese data provide the proof-of-principle that RSDN can be performed using an off-the-shelf saline-irrigated RFA catheter

Leadless pacemaker versus transvenous single-chamber pacemaker therapy: A propensity score-matched analysis

Background: The recent introduction of leadless pacemakers (PMs) was aimed to eliminate transvenous lead- and pocket-related complications. While the initial results with the leadless PMs seem promising, the nonrandomized nature, limited implant experience of operators, and short follow-up period of these studies preclude a simple comparison to transvenous PMs. Objectives: The objective of this study was to provide a balanced comparison of leadless and transvenous single-chamber PM therapies through a propensity score-matched analysis. Methods: Leadless patients from 3 experienced leadless implant centers were propensity score-matched to VVI-R patients from a contemporary prospective multicenter transvenous PM registry. The primary outcome was device-related complications that required invasive intervention during mid-term follow-up. Separate analyses including and excluding PM advisory–related complications were performed. Results: A total of 635 patients were match-eligible (leadless: n = 254; transvenous: n = 381), of whom 440 patients (median age 78 years; interquartile range 70–84 years; 61% men) were successfully matched (leadless: n = 220 vs transvenous: n = 220). The complication rate at 800 days of follow-up was 0.9% (95% confidence interval [CI] 0%–2.2%) in the leadless group vs 4.7% (95% CI 1.8%–7.6%) in the transvenous group when excluding PM advisory–related complications (P =.02). When including these PM advisory–related complications, the complication rate at 800 days increased to 10.9% (95% CI 4.8%–16.5%) in the leadless group vs 4.7% (95% CI 1.8%–7.6%) in the transvenous group (P =.063). Conclusion: This study reveals favorable complication rates for leadless compared to transvenous single-chamber pacing therapy at mid-term follow-up in a propensity score-matched cohort. When including PM advisory–related complications, this advantage is no longer observed

Chronic performance of a leadless cardiac pacemaker: 1-year follow-up of the LEADLESS trial

A leadless cardiac pacemaker (LCP) system was recently introduced to overcome lead-related complications of conventional pacing systems. To date, long-term results of an LCP system are unknown. The aim of this study was to assess the complication incidence, electrical performance, and rate response characteristics within the first year of follow-up of patients implanted with an LCP. We retrospectively assessed intermediate-term follow-up data for 31 of 33 patients from the LEADLESS trial cohort who had an indication for single-chamber pacing and received an LCP between December 2012 and April 2013. The mean age of the cohort was 76 ± 8 years, and 65% were male. Between 3 and 12 months of follow-up, there were no pacemaker-related adverse events reported. The pacing performance results at 6- and 12-month follow-up were, respectively, as follows: mean pacing threshold (at a 0.4-ms pulse width), 0.40 ± 0.26 V and 0.43 ± 0.30 V; R-wave amplitude 10.6 ± 2.6 mV and 10.3 ± 2.2 mV; and impedance 625 ± 205 Ω and 627 ± 209 Ω. At the 12-month follow-up in 61% of the patients (n = 19 of 31), the rate response sensor was activated, and an adequate rate response was observed in all patients. The LCP demonstrates very stable performance and reassuring safety results during intermediate-term follow-up. These results support the use of the LCP as a promising alternative to conventional pacemaker systems. Continued evaluation is warranted to further characterize this system. (Evaluation of a New Cardiac Pacemaker; NCT01700244