Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

Background. Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods. Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results. 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion. Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399

Underlying heart diseases and acute COVID-19 outcomes

Background: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). Methods: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. Results: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0–78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29–2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001).Conclusions: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

BackgroundMost evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19.MethodsAnalysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses.Results7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM.ConclusionHospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399

Comparative efficacy of novobiocin and amoxicillin in experimental sepsis caused by β-lactam-susceptible and highly resistant pneumococci.

[EN]Manuscript accepted version for publication. [ES]Versión aceptada del manuscrito para su publicación.Therapeutic alternatives are needed against infections caused by highly multidrug-resistant Streptococcus pneumoniae. Novobiocin, an old antibiotic, was tested in vitro and in a murine sepsis model against one amoxicillin-susceptible and three amoxicillin-resistant strains [minimum inhibitory concentrations (MICs) 8–64mg/L]. Novobiocin MICs for all strains were 0.25–0.5mg/L. In sepsis, novobiocin and amoxicillin were evaluated at 25, 50, 100 and 200mg/kg given at 1, 5, 24 and 48h post bacterial challenge. The most effective regimens in animals infected with the amoxicillin-susceptible strain were 200mg/kg novobiocin and 25mg/kg amoxicillin, achieving 100% survival and undetectable organisms in the peritoneum. Among mice infected with amoxicillin-resistant S. pneumoniae, 200mg/kg novobiocin gave the highest protection (90–100% survivors), followed by 200mg/kg amoxicillin (60–100%), 100mg/kg novobiocin (50–87.5%) and 50mg/kg amoxicillin (14.3–25%). The killing effect of antibiotics in the peritoneum (mean Δlog10 colony-forming units/mL between treated and control mice) was as follows: 200mg/kg novobiocin (−6.6)>200mg/kg amoxicillin (−5.6)>100mg/kg novobiocin (−3.7)>50mg/kg amoxicillin (−0.7). Total plasma and ultrafiltrate pharmacokinetics of novobiocin (200mg/kg, single dose) in non-infected mice showed, respectively, half-lives of 151min and 215min, area under the concentration–time curves (AUCs) of 945.0mg h/L and 136.6mg h/L and maximal concentrations of 147mg/L and 18mg/L. Novobiocin may be a promising agent for therapy of highly β-lactam-resistant pneumococcal infections.Research contracts were received by VR-C (COMBACT-CM, S-BIO-0260/2006) and by GdP (CPI/0305/2 007 attached to COMBACT-CM), both from Comunidad Autónoma de Madrid, Spain. VR-C is currently supported by a research contract from the Subprogram Juan de La Cierva (JCI-2008-02690; Ministerio de Ciencia e Innovación Tecnológica, Spain). LH received a grant from the Fundación Conchita Rábago (Madrid, Spain), and PN from the Alan program (European Union). This work was performed under the Research Collaboration Agreement between the Consejo Superior de Investigaciones Científicas and the Fundación Jiménez Díaz.Peer reviewe