ABSTRACT
Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual’s medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over one year.Methods/Design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T-cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T-cell response and neutralising capacity will be assessed.The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.
Subject(s)
COVID-19ABSTRACT
BACKGROUND: From March to April 2020, Spain was the center of the SARS-CoV-2 pandemic, particularly Madrid with approximately 30% of the cases in Spain. The aim of this study is to report the suspected serious adverse drug reactions (SADRs) in COVID-19 patients versus non-COVID-19 patients detected by the prospective pharmacovigilance program based on automatic laboratory signals (ALSs) in the hospital (PPLSH) during that period. We also compared the results with the suspected SADRs detected during the same period for 2019. METHODS: All ALSs that reflected potential SADRs (including neutropenia, pancytopenia, thrombocytopenia, anemia, eosinophilia, leukocytes in cerebrospinal fluid, hepatitis, pancreatitis, acute kidney injury, rhabdomyolysis and hyponatremia were prospectively monitored in hospitalized patients during the study periods. We analyzed the incidence and the distribution of causative drugs for the COVID-19 patients. RESULTS: The incidence rate of SADRs detected in the COVID-19 patients was 760.63 (95% CI 707.89–816.01) per 10,000 patients, 4.75-fold higher than the SADR rate for non-COVID-19 patients (160.15 per 10,000 patients,95% CI 137.09–186.80), and 5.84-fold higher than the SADR rate detected for the same period in 2019 (130.19 per 10,000 patients, 95% CI 109.53–154.36). The most frequently related drugs were tocilizumab (59.84%), dexketoprofen (13.93%), azithromycin (8.43%), lopinavir-ritonavir (7.35%), dexamethasone (7.62%), and chloroquine/hydroxychloroquine (6.91%). CONCLUSIONS: The incidence rate of SADRs detected by the PPSLH in patients with COVID-19 was 4.75-fold higher than that of the non-COVID-19 patients. Caution is recommended when using medications for COVID-19 patients, especially drugs that are hepatotoxic, myotoxic, and those that induce thromboembolic events.
Subject(s)
COVID-19ABSTRACT
BACKGROUND Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the Madrid region. This article describes the first 2226 consecutive adult patients with COVID-19 admitted to the La Paz University Hospital in Madrid. METHODS Our cohort included all consecutively admitted patients who were hospitalized and who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from February 25th (first case admitted) to April 19th, 2020. Data was entered manually into an electronic case report form, which was monitored prior to the analysis. RESULTS We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients median age was 61 years; 51.8% were women. The most common comorbidity was arterial hypertension (41.3%). The most common symptoms on admission were fever (71.2%). The median time from disease onset to hospital admission was 6 days. Overall mortality was 20.7% and was higher in men (26.6% vs 15.1%). Seventy-five patients with a final outcome were transferred to the ICU (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. CONCLUSIONS We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male gender, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes.