mRNA-1273 SARS-CoV-2 vaccine safety and COVID-19 risk perception in recently transplanted allogeneic hematopoietic stem cell transplant recipients.

PURPOSE: This study aims to describe the incidence and severity of adverse events (AEs) following the mRNA-1273 SARS-CoV-2 vaccine and explore the risk perception of COVID-19 in allogeneic hematopoietic stem cell transplant (HCT) recipients. METHODS: We performed a single-center prospective study including recently transplanted (< 2 years post-infusion) allogeneic HCT recipients. AEs were assessed through phone calls and graded from 0 to 4, while COVID-19 risk perception was measured using the Brief Illness Perception Questionnaire (BIP-Q5). RESULTS: Fifty-four HCT recipients were evaluated. Incidence and grades of AE (94.4% and 85.2% after the first and second dose, respectively) were similar to those described in the general population. The most common AE was pain at the site of injection. Three patients (5.6%) developed a grade ≥ 3 AE. Vaccine-related cytopenias and graft-versus-host disease flares were not observed. Female sex (OR 3.94, 95% CI 1.14-13.58, p = 0.03) and time since HCT (per month since HCT: OR 1.09, 95% CI 1.01-1.18, p = 0.04) were associated with the occurrence of any AE. The patients' risk perception level of COVID-19 decreased over time (p < 0.05). CONCLUSION: Our study confirms that the mRNA-1273 SARS-CoV-2 vaccine is safe in recent HCT recipients and suggests that the perceived risk of COVID-19 decreases over time.

Immune Response and Safety of SARS-CoV-2 mRNA-1273 Vaccine in Patients With Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG. METHODS: We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates. RESULTS: Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46-24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13-7.13, p = 0.024). DISCUSSION: Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels.

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial.

INTRODUCTION: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. METHODS: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.

Epidemiological characteristics and outcomes of COVID-19 cases: mortality inequalities by socio-economic status, Barcelona, Spain, 24 February to 4 May 2020.

BackgroundPopulation-based studies characterising outcomes of COVID-19 in European settings are limited, and effects of socio-economic status (SES) on outcomes have not been widely investigated. AimWe describe the epidemiological characteristics of COVID-19 cases, highlighting incidence and mortality rate differences across SES during the first wave in Barcelona, Catalonia, Spain.MethodsThis population-based study reports individual-level data of laboratory-confirmed COVID-19 cases diagnosed from 24 February to 4 May 2020, notified to the Public Health Agency of Barcelona and followed until 15 June 2020. We analysed end-of-study vital status and the effects of chronic conditions on mortality using logistic regression. Geocoded addresses were linked to basic health area SES data, estimated using the composed socio-economic index. We estimated age-standardised incidence, hospitalisation, and mortality rates by SES.ResultsOf 15,554 COVID-19-confirmed cases, the majority were women (n = 9,028; 58%), median age was 63 years (interquartile range: 46-83), 8,046 (54%) required hospitalisation, and 2,287 (15%) cases died. Prevalence of chronic conditions varied across SES, and multiple chronic conditions increased risk of death (≥ 3, adjusted odds ratio: 2.3). Age-standardised rates (incidence, hospitalisation, mortality) were highest in the most deprived SES quartile (incidence: 1,011 (95% confidence interval (CI): 975-1,047); hospitalisation: 619 (95% CI: 591-648); mortality: 150 (95% CI: 136-165)) and lowest in the most affluent (incidence: 784 (95% CI: 759-809); hospitalisation: 400 (95% CI: 382-418); mortality: 121 (95% CI: 112-131)).ConclusionsCOVID-19 outcomes varied markedly across SES, underscoring the need to implement effective preventive strategies for vulnerable populations.