Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov ( NCT04860739 ), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

Aims Data regarding impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) is lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and prior diagnosis of HF. Also, to identify predictors and prognostic implications for AHF decompensations during hospital admission and to determine whether there was a correlation between withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization. Methods and results A total of 3080 consecutive patients with confirmed COVID‐19 infection and at least 30‐day follow‐up were analyzed. Patients with previous history of CHF (152, 4.9%), were more prone to develop AHF (11.2% vs 2.1%; p<0.001) and had higher levels of NT‐proBNP. Also, previous CHF group had higher mortality rates (48.7% vs 19.0%; p<0.001). In contrast, 77 patients (2.5%) were diagnosed of AHF and the vast majority (77.9%) developed in patients without history of HF. Arrhythmias during hospital admission and CHF were main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs 19.7%; p<0.001). Finally, withdrawal of beta‐blockers, mineralocorticoid antagonists and ACE/ARB inhibitors was associated with a significant increase of in‐hospital mortality. Conclusions Patients with COVID‐19 have a significant incidence of AHF, entity that carries within a very high mortality. Moreover, patients with history of CHF are prone to develop acute decompensation after COVID‐19 diagnosis. Withdrawal of GDMT was associated with higher mortality.

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.

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 region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. Methods: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered 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, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The 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 intensive care unit (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 sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes.

Aims Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID‐19) has been performed. However, data regarding natriuretic peptides are scarce. N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT‐proBNP concentrations using a large cohort of patients with COVID‐19, and to investigate its association with prognosis. Methods and results Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and available NT‐proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1‐month follow‐up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow‐up of 53 (18–62) days. Of those, 192 (48.5%) presented NT‐proBNP levels above the recommended cut‐off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT‐proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT‐proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT‐proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13–1.44, per logarithmic unit). Conclusion NT‐proBNP is frequently elevated in COVID‐19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.