Previous studies that assessed risk factors for venous thromboembolism (VTE) in COVID-19 patients have shown inconsistent results. Our aim was to investigate VTE predictors by both logistic regression (LR) and machine learning (ML) approaches, due to their potential complementarity. This cohort study of a large Brazilian COVID-19 Registry included 4120 COVID-19 adult patients from 16 hospitals. Symptomatic VTE was confirmed by objective imaging. LR analysis, tree-based boosting, and bagging were used to investigate the association of variables upon hospital presentation with VTE. Among 4,120 patients (55.5% men, 39.3% critical patients), VTE was confirmed in 6.7%. In multivariate LR analysis, obesity (OR 1.50, 95% CI 1.11–2.02); being an ex-smoker (OR 1.44, 95% CI 1.03–2.01); surgery ≤ 90 days (OR 2.20, 95% CI 1.14–4.23); axillary temperature (OR 1.41, 95% CI 1.22–1.63); D-dimer ≥ 4 times above the upper limit of reference value (OR 2.16, 95% CI 1.26–3.67), lactate (OR 1.10, 95% CI 1.02–1.19), C-reactive protein levels (CRP, OR 1.09, 95% CI 1.01–1.18); and neutrophil count (OR 1.04, 95% CI 1.005–1.075) were independent predictors of VTE. Atrial fibrillation, peripheral oxygen saturation/inspired oxygen fraction (SF) ratio and prophylactic use of anticoagulants were protective. Temperature at admission, SF ratio, neutrophil count, D-dimer, CRP and lactate levels were also identified as predictors by ML methods. By using ML and LR analyses, we showed that D-dimer, axillary temperature, neutrophil count, CRP and lactate levels are risk factors for VTE in COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-022-03002-z.

The majority of early prediction scores and methods to predict COVID-19 mortality are bound by methodological flaws and technological limitations (e.g., the use of a single prediction model). Our aim is to provide a thorough comparative study that tackles those methodological issues, considering multiple techniques to build mortality prediction models, including modern machine learning (neural) algorithms and traditional statistical techniques, as well as meta-learning (ensemble) approaches. This study used a dataset from a multicenter cohort of 10,897 adult Brazilian COVID-19 patients, admitted from March/2020 to November/2021, including patients [median age 60 (interquartile range 48–71), 46% women]. We also proposed new original population-based meta-features that have not been devised in the literature. Stacking has shown to achieve the best results reported in the literature for the death prediction task, improving over previous state-of-the-art by more than 46% in Recall for predicting death, with AUROC 0.826 and MacroF1 of 65.4%. The newly proposed meta-features were highly discriminative of death, but fell short in producing large improvements in final prediction performance, demonstrating that we are possibly on the limits of the prediction capabilities that can be achieved with the current set of ML techniques and (meta-)features. Finally, we investigated how the trained models perform on different hospitals, showing that there are indeed large differences in classifier performance between different hospitals, further making the case that errors are produced by factors that cannot be modeled with the current predictors.

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ObjectiveTo provide a thorough comparative study among state-of-the-art machine learning methods and statistical methods for determining in-hospital mortality in COVID-19 patients using data upon hospital admission; to study the reliability of the predictions of the most effective methods by correlating the probability of the outcome and the accuracy of the methods; to investigate how explainable are the predictions produced by the most effective methods.Materials and MethodsDe-identified data were obtained from COVID-19 positive patients in 36 participating hospitals, from March 1 to September 30, 2020. Demographic, comorbidity, clinical presentation and laboratory data were used as training data to develop COVID-19 mortality prediction models. Multiple machine learning and traditional statistics models were trained on this prediction task using a folded cross-validation procedure, from which we assessed performance and interpretability metrics.ResultsThe Stacking of machine learning models improved over the previous state-of-the-art results by more than 26% in predicting the class of interest (death), achieving 87.1% of AUROC and macro F1 of 73.9%. We also show that some machine learning models can be very interpretable and reliable, yielding more accurate predictions while providing a good explanation for the ‘why’.ConclusionThe best results were obtained using the meta-learning ensemble model – Stacking. State-of the art explainability techniques such as SHAP-values can be used to draw useful insights into the patterns learned by machine-learning algorithms. Machine-learning models can be more explainable than traditional statistics models while also yielding highly reliable predictions.