Safety and performance of conduction system pacing: Real-world experience from a product surveillance registry.

BACKGROUND: Conduction system pacing (CSP), including His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has been used as an alternative for pacemaker indicated patients requiring ventricular pacing. OBJECTIVE: The purpose of this study was to characterize the safety and performance of HBP and LBBAP among patients enrolled in the Medtronic product surveillance registry (PSR). METHODS: This observational analysis included patients who underwent pacemaker implantations for HBP or LBBAP with a Medtronic Model 3830 lead between January 2019 and December 2023 in the Medtronic PSR. The primary outcomes were lead-related complications and pacing capture threshold. Baseline characteristics, R-wave amplitude, impedance, and all-cause mortality were summarized. RESULTS: A total of 2342 patients were included across 77 centers (mean age 74 years; 38.9% female). Of the patients implanted with a 3830 lead for CSP, 64.1% (n = 1502) had LBBAP placement and 35.9% (n = 840) had HBP placement. The most commonly reported indications for CSP were sinus node dysfunction (67.0%) and atrioventricular block (57.2%). LBBAP had lower pacing thresholds, higher R-wave sensing, and higher impedance (all P <.001) through 30 months. At 36 months postimplant, the lead complication rate for LBBAP and HBP was 2.5% and 6.3%, ,respectively with no difference in all-cause mortality. CONCLUSION: In a multicenter cohort of LBBAP and HBP patients treated with the catheter-delivered 3830 lead, lead-related complication rates were low and electrical parameters were stable through 30 months.

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

OBJECTIVES: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. METHODS: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. RESULTS: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. CONCLUSION: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Cytokine profile of anti-spike CD4+T cells predicts humoral and CD8+T cell responses after anti-SARS-CoV-2 mRNA vaccination.

Coordinating immune responses - humoral and cellular - is vital for protection against severe Covid-19. Our study evaluates a multicytokine CD4+T cell signature's predictive for post-vaccinal serological and CD8+T cell responses. A cytokine signature composed of four cytokines (IL-2, TNF-α, IP10, IL-9) excluding IFN-γ, and generated through machine learning, effectively predicted the CD8+T cell response following mRNA-1273 or BNT162b2 vaccine administration. Its applicability extends to murine vaccination models, encompassing diverse immunization routes (such as intranasal) and vaccine platforms (including adjuvanted proteins). Notably, we found correlation between CD4+T lymphocyte-produced IL-21 and the humoral response. Consequently, we propose a test that offers a rapid overview of integrated immune responses. This approach holds particular relevance for scenarios involving immunocompromised patients because they often have low cell counts (lymphopenia) or pandemics. This study also underscores the pivotal role of CD4+T cells during a vaccine response and highlights their value in vaccine immunomonitoring.

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination.

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection.

Background: Understanding factors affecting the size and the evolution of the HIV reservoir is essential for the development of curative strategies. This study aimed to assess the impact of antiretroviral therapy (ART) initiated during primary infection (PHI) vs chronic infection (CHI) on the levels and dynamics of integrated HIV-1 DNA, a biomarker of viral persistence. Methods: Integrated and total HIV-1-DNA were measured in the blood of 92 patients treated during PHI (early group) and 41 during CHI (deferred group), at diagnosis, ART initiation, and 12-24 months on treatment. Results: On ART, detectable (>1.78 log10 copies/106 PBMCs) integrated HIV-1 DNA levels were significantly lower in the early vs deferred group (2.99 log10vs 3.29 log10,p = 0.005). The proportion of undetectable integrated HIV-1 DNA tended to be higher in the early group vs deferred group (61 % vs 46 %; p = 0.133). Conclusion: Treatment initiated at PHI limits the levels of integrated HIV-1 DNA in blood. However, initiating treatment at CHI does not allow reaching such low levels in most patients, probably because the stable proviruses at that stage are present in the less prone to elimination long-lived cells. Thus, early ART could provide an opportunity to preparing for functional cure and eradication strategies.