Lung Ultrasound Score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort

Objetivos: Establecer diferentes puntos de corte basados ​​en el Lung Ultrasound Score (LUS) para clasificar la gravedad de la neumonía COVID-19. Métodos: Inicialmente, realizamos una revisión sistemática entre los puntos de corte LUS propuestos previamente. Estos resultados fueron validados por una cohorte prospectiva de un unicéntrica de pacientes adultos con infección confirmada por SARS-CoV-2. Las variables analizadas fueron mala evolución y mortalidad a los 28 días. Resultados: De 510 artículos, se incluyeron 11. Entre los puntos de corte propuestos en los artículos incluidos, solo LUS >15 pudo ser validado para su objetivo original, demostrando también la relación más fuerte con mala evolución (odds ratio [OR] = 3,636, intervalo de confianza [IC] 1.411-9.374). Respecto a nuestra cohorte, se incluyeron 127 pacientes. En estos pacientes, la LUS se asoció estadísticamente con mala evolución (OR = 1,303, IC 1,137-1,493) y con mortalidad a los 28 días (OR = 1,024, IC 1,006-1,042). LUS > 15 mostró el mejor rendimiento diagnóstico al elegir un único punto de corte en nuestra cohorte (área bajo la curva 0,650). LUS ≤7 mostró una alta sensibilidad para descartar mal resultado (0,89, IC 0,695-0,955), mientras que LUS >20 reveló gran especificidad para predecir mala evolución (0,86, IC 0,776-0,917). Conclusiones: LUS es un buen predictor de mala evolución y mortalidad a 28 días en COVID-19. LUS ≤7 se asocia con neumonía leve, LUS 8-20 con neumonía moderada y ≥20 con neumonía grave. Si se utilizara un único punto de corte, LUS > 15 sería el que mejor discriminaría la enfermedad leve de la grave.

New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations (preprint)

Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study. (preprint)

Introduction: Little evidence appears to exists for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p=0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients, and may improve their prognosis.