Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Background Coronavirus disease COVID-19 produces a predominantly pulmonary affection, being cardiac involvement an important component of the multiorganic dysfunction. At the moment there are few reports about the behavior of echocardiographic images in the patients who have the severe forms of the disease. Objective Identify the echocardiographic prognostic markers for death within 60 days in patients hospitalized in intensive care. Methods A single-center prospective cohort was made with patients hospitalized in intensive care for COVID-19 confirmed via polymerase chain reaction who got an echocardiogram between May and October 2020. A Cox multivariate model was plotted reporting the HR and confidence intervals with their respective p values for clinical and echocardiographic variables. Results Out of the 326 patients included, 153 patients got an echocardiogram performed on average 6.8 days after admission. The average age was 60.7, 47 patients (30.7%) were females and 67 (44.7%) registered positive troponin. 91 patients (59.5%) died. The univariate analysis identified TAPSE, LVEF, pulmonary artery systolic pressure, acute cor pulmonale, right ventricle diastolic dysfunction, and right ventricular dilatation as variables associated with mortality. The multivariate model identified that the acute cor pulmonale with HR= 4.05 (CI 95% 1.09 - 15.02, p 0.037), the right ventricular dilatation with HR= 3.33 (CI 95% 1.29 - 8.61, p 0.013), and LVEF with HR= 0.94 (CI 95% 0.89 - 0.99, p 0.020) were associated with mortality within 60 days. Conclusions In patients hospitalized in the intensive care unit for COVID-19, the LVEF, acute cor pulmonale and right ventricular dilatation are prognostic echocardiographic markers associated with death within 60 days.

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Antecedentes: el síndrome coronario agudo es una emergencia clínica que se manifiesta principalmente por dolor torácico. Su diagnóstico representa un desafío clínico y su reconocimiento temprano es fundamental para el tratamiento. Objetivo: describir las características clínicas, identificar abordajes terapéuticos y conocer los desenlaces de los pacientes con diagnóstico definitivo de síndrome coronario agudo hospitalizados por el servicio de medicina interna y cardiología entre el 1° de enero de 2009 hasta 31 de diciembre de 2010 en el Hospital San José. Métodos: se realizó una descripción de una cohorte de pacientes con diagnóstico de síndrome coronario agudo (infarto miocárdico con y sin elevación del segmento ST y angina inestable). Se analizaron variables demográficas, características clínicas, tratamiento y desenlaces a los cuales se calcularon promedio, desviación estándar y proporciones según la naturaleza de las mismas. Resultados: se reportan 133 pacientes. El 63% correspondió a hombres, el promedio de edad fue de 64.8 años. La frecuencia de eventos fue 45.9% IMEST, 39% IMSEST y 15.1% anginas inestables. El 96.2% de los pacientes consultó por dolor torácico, 50.7% presentaron dolor en las primeras seis horas de evolución. El 93% recibió betabloqueador, 88% IECA, 87% clopidogrel y 97% ASA. Se trombolizó al 82% de los pacientes en ventana. La mortalidad intrahospitalaria fue del 8.7%. Conclusiones: en la población estudiada predominó el síndrome coronario agudo sin elevación del segmento ST. La mayoría de pacientes consultaron por dolor torácico retroesternal, en las primeras horas de inicio. El porcentaje de uso de los medicamentos fue adecuado. La reperfusión inmediata en pacientes con IMEST fue alta, sin embargo aún tenemos pacientes que no se benefician de esta terapia y el uso de angioplastias primarias fue muy bajo.

Extensive evidence was found that shows that using intelligent systems tools achieves a greater degree of accuracy than some clinical algorithms or scales and, thus, should be considered appropriate tools for supporting diagnostic decisions of acute coronary syndromes.

Introduction: Research about the risk factors associated with community-acquired acute kidney injury (CA-AKI) in acute medical diseases is scarce. Data extrapolation from surgical to medical illnesses is questionable. Objectives: To evaluate potential risk factors and hospital outcomes associated with a CA-AKI in medical illnesses. Methods: We performed an unmatched nested case-control study from a previous prospective cohort study. We included adult patients with acute illnesses treated with internal medicine. Cases were defined as patients with a CA-AKI diagnosis upon hospital admission, and controls included patients from the same cohort who did not develop AKI during the first 5 days of hospitalisation. A logistic regression model was used to assess the association between potential risk factors and CA-AKI. Results: A total of 868 patients were included in the study (223 cases and 645 controls). The median age was 65 years (interquartile range 50-78). In a logistic regression model, the risk factors associated with CA-AKI included chronic kidney disease (CKD; OR 6.27; 95% CI 2.95-13.3, p < 0.001), ≥65 years old (OR 1.72; 95% CI 1.16-2.57, p = 0.007), acute bacterial infection (OR 1.95; 95% CI 1.36-2.80, p < 0.001), hypovolaemia (OR 1.88; 95% CI 1.32-2.69, p < 0.001), pre-hospital nephrotoxic drugs (OR 1.77; 95% CI 1.23-2.55, p = 0.002), anaemia (OR 1.49; 95% CI 1.03-2.14, p = 0.031) and systolic blood pressure (SBP) < 107 mm Hg (OR 2.25; 95% CI 1.38-3.67, p = 0.001). A significant interaction between CKD and age was found (p = 0.017) and included in the model (patients with CKD and ≥65 years old [OR 10.85; 95% CI 4.14-28.41, p < 0.001]). The area under the receiver operating characteristic curve of the final model was 0.743. Conclusions: CKD is strongly associated with CA-AKI upon hospital admission in medical illnesses patients. Older age enhances the risk of CA-AKI in patients with CKD. Other risk factors include pre-hospital nephrotoxic drugs, acute bacterial infection, anaemia, low SBP and hypovolaemia.

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Introducción: la falla cardiaca (FC) es una de las principales causas de morbimortalidad a nivel mundial, la cual ha experimentado aumento gradual de su incidencia sin variación importante en su desenlace en las dos últimas décadas. En Colombia muy pocos estudios evalúan factores asociados a mortalidad por falla cardiaca. Métodos: estudio de cohorte prospectivo en el que se incluyeron pacientes con diagnóstico de falla cardiaca descompensada al momento del ingreso a urgencias, entre febrero de 2010 y marzo de 2013. Se calculó el tamaño de muestra y se realizó un análisis multivariado para la evaluación de los factores de riesgo asociados a mortalidad intrahospitalaria y a 30 días. Resultados: se incluyeron 462 pacientes. La mortalidad hospitalaria fue de 8.9% y a 30 días de 13.8%, en el modelo multivariado para el desenlace mortalidad intrahospitalaria se observó que la única variable con significancia estadística fue el BUN ≥43 mg/dL (OR, 3.45 [IC 95% 1.54-7.74], p= 0.003). Para la mortalidad a 30 días, la estancia hospitalaria >5 días (OR, 2.23 [IC 95% 1.204.12], p= 0.011), el BUN ≥43 mg/dL (OR, 2.55 [IC 95% 1.31-4.94], p= 0.005) y el NT-proBNP ≥ 4630 pg/dL (OR, 2.47 [IC 95% 1.30-4.70], p= 0.006). Conclusiones: la mortalidad intrahospitalaria de los pacientes con falla cardiaca descompensada en la población evaluada fue alta. En los análisis multivariados, se encontró que el BUN ≥ 43 mg/dL fue el único factor de riesgo independiente asociado a mortalidad intrahospitalaria; mientras que la mortalidad a 30 días se relacionó además con el NT-proBNP y la estancia hospitalaria superior a cinco días