Clinical prediction rules for adverse outcomes in patients with SARS COV-2 infection by the omicron variant (preprint)

Background: Factors related to an adverse evolution in COVID19 infection are needed for proper decision making. We try to identify factors related to hospitalization, ICU admission, and mortality related to the infection. Methods. Retrospective cohort study of patients with SARS-CoV-2 infection from March 1st 2020 to January 9th 2022. The sample was randomly divided into two subsamples, for the purposes of derivation and validation of the prediction rule, until omicron variant appearance and afterwards, respectively. Data collected for this study included sociodemographic data, baseline comorbidities and treatments, and other background data. Multivariable logistic regression models using Lasso logistic regression were used . Results. In the multivariable models, older age, male, peripheral vascular disease, heart failure, heart disease, cerebrovascular, dementia, liver, kidney, diabetes, hemiplegia, interstitial pulmonary disease, cystic fibrosis, malignant tumors, as well as diuretics and the chronic systemic use of steroids were common predictive factors of death. Similar predictors, except liver disease, plus arterial hypertension, were also related to adverse evolution. Similar predictors to the previous, including liver disease, plus dyslipidemia, inflammatory bowel disease, respiratory diseases, and the basal prescription of NSAIDs, heparin, bronchodilators, or immunosuppressants were related to hospital admission. All risk scores developed had AUCs from 0.79 (hospital admission) to 0.94 (death) in the validation in the omicron sample. Conclusions. We propose three risk scales for adverse outcomes and hospital admission easy to calculate and with high predictive capacity, which also work with the current omicron variant, which can help manage patients in primary, emergency, and hospital care.

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.

COVID-19 IN YOUNG AND MIDDLE-AGED ADULTS. PREDICTORS OF POOR OUTCOME AND CLINICAL DIFFERENCES. (preprint)

ABSTRACT Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. Objective: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore potential differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. Methods: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of “poor outcome” including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen therapies and/or death. Results: We identified 513 patients <65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, chest pain, anosmia, low oxygen saturation, high LDH and lymphocyte count <800/mL. Conclusions: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are more common and protective. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.