ABSTRACT
Background: Since January 2021, the two in Switzerland approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines tozinameran (Pfizer/Biontech) and elasomeran (Moderna) have been used to vaccinate the Swiss population. These vaccines were found to be safe in licensing trials with excellent efficacy of 95% and 94% in terms of preventing COVID-19 illness 14 days after the second vaccination. However, randomized evidence on the comparative effectiveness of both vaccines in immunocompromised patients is currently lacking. Methods: We conducted a parallel, two-arm (allocation 1:1) open-label, non-inferiority randomized clinical trial (RCT) nested into the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS). Patients living with HIV and solid organ transplant recipients (i.e. lung and kidney) from these cohorts were randomized to receive either tozinameran or elasomeran. The primary endpoint was an antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain using Elecsys® Anti-SARS-CoV-2 S assay from Roche (binary, cut-off ≥0.8 Units/ml) 12 weeks after first vaccination (8 weeks after second vaccination). Secondary outcomes were immune response measured with the Antibody CORonavirus Assay (ABCORA), clinical and safety outcomes. Results: A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 HIV patients and 71 solid organ transplant recipients). Antibody response was for elasomeran 92.1% (95% CI 88.4-95.8%;186/202) and for tozinameran 94.3% (95% CI 91.2-97.4%;198/210;difference:-2.2%;95% CI-7.1-2.7%), fulfilling non-inferiority of elasomeran. Overall, neutralization activity to SARS-CoV-2 Wuhan HU-1 strain was estimated to 96.5% (95% CI 94.5-98.4%) in HIV patients and 21.1% (95% CI 11.6-30.6%) in solid organ transplant recipients. 5 SARS-CoV-2 infections occurred (3 elasomeran;2 tozinameran) and 18 serious adverse event occurred (9 elasomeran;9 tozinameran). Conclusion: In immunocompromised patients the antibody response of elasomeran was comparable to tozinameran. People living with HIV had in general a sufficient immune response while a high proportion of transplant recipients had no immune response. Nearly 80% of patients with solid organ transplant have not developed neutralizing activity and need booster vaccination.
ABSTRACT
Background: Arrhythmias may often be a result of heart failure, but they can also cause left-ventricular systolic dysfunction (LVSD), thereby presenting as arrhythmia-induced cardiomyopathy (AIC). AIC-diagnosis is established retrospectively when LVSD normalizes or improves significantly over time following rhythm restoration. However, the prevalence and most importantly the time course of this relevant disease remain unclear and hence merit investigation to enable the correct diagnosis. Purpose: Therefore, our aim was to evaluate a) the occurrence of AIC in this clinical relevant cohort of patients with newly diagnosed and otherwise unexplainable LVSD and concomitant tachycardia and b) the time needed to fulfill the diagnostic criteria of AIC in order to facilitate a diagnostic algorithm. Method: We prospectively screened patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (i.e. left ventricular ejection fraction (LVEF) <50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) >100/min) in 3 cardiological centers. Coronary angiography and cardiac magnetic resonance imaging were performed to exclude other causes for LVSD. Patients underwent a rhythm control strategy in accordance to the local clinical pathways. LVEF was assessed by echocardiography at presentation and at follow-up (FU) visits after 2, 4, and 6 months. Patients who lost sinus rhythm (SR) during FU were excluded. Patients with any increase of ≥15% in absolute EF or an EF ≥50% with an improvement of ≥10% after 6 months of FU were assigned to the AICgroup, which is a common definition of AIC. All others were assigned to an idiopathic DCM-group as final comparator. Results: 68 patients were eligible, 18 of them were excluded: 1 lost to follow-up, 1 PCI, 2 COVID-19, 1 diagnosed cancer, 1 withdraw consent and 12 lost SR. Thus, our sample consists of a total of 50 patients. At presentation, mean±SD HR was 121±17/min. After rhythm therapy, HR normalized (67±10/min) and LVEF increased in both groups, see fig. 1. Surprisingly, only 9 patients did not fulfill the AIC-criteria in this specific collective resulting in a prevalence of 82% (95%-CI: 68% - 92%). This high prevalence of AIC underlines the importance of the disease. 2 and 4 months after rhythm intervention, 58% and 73% of patients fulfilled AIC-criteria (fig. 2). The sensitivity for detection of AIC by echocardiographic LVEF-measurement at months 2 and 4 of FU was 65% and 86% with a specificity of 100%, emphasizing that a FU of 6 months is necessary to certainly distinguish between AIC and idiopathic DCM. Conclusion: The prevalence of AIC in patients with newly diagnosed and otherwise unexplainable LVSD with concomitant tachycardia is 82%. Analysis of the time course of AIC clearly suggests that the final diagnosis cannot be established before 6 months after successful rhythm restoration. These results may help to improve diagnosis of AIC in daily clinical practice.