Fernando Antonio Botoni

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.

The COVID-19 pandemic caused unprecedented pressure over health care systems worldwide. Hospital-level data that may influence the prognosis in COVID-19 patients still needs to be better investigated. Therefore, this study analyzed regional socioeconomic, hospital, and intensive care units (ICU) characteristics associated with in-hospital mortality in COVID-19 patients admitted to Brazilian institutions. This multicenter retrospective cohort study is part of the Brazilian COVID-19 Registry. We enrolled patients ≥ 18 years old with laboratory-confirmed COVID-19 admitted to the participating hospitals from March to September 2020. Patients’ data were obtained through hospital records. Hospitals’ data were collected through forms filled in loco and through open national databases. Generalized linear mixed models with logit link function were used for pooling mortality and to assess the association between hospital characteristics and mortality estimates. We built two models, one tested general hospital characteristics while the other tested ICU characteristics. All analyses were adjusted for the proportion of high-risk patients at admission. Thirty-one hospitals were included. The mean number of beds was 320.4 ± 186.6. These hospitals had eligible 6556 COVID-19 admissions during the study period. Estimated in-hospital mortality ranged from 9.0 to 48.0%. The first model included all 31 hospitals and showed that a private source of funding (β = − 0.37; 95% CI − 0.71 to − 0.04; p = 0.029) and location in areas with a high gross domestic product (GDP) per capita (β = − 0.40; 95% CI − 0.72 to − 0.08; p = 0.014) were independently associated with a lower mortality. The second model included 23 hospitals and showed that hospitals with an ICU work shift composed of more than 50% of intensivists (β = − 0.59; 95% CI − 0.98 to − 0.20; p = 0.003) had lower mortality while hospitals with a higher proportion of less experienced medical professionals had higher mortality (β = 0.40; 95% CI 0.11–0.68; p = 0.006). The impact of those association increased according to the proportion of high-risk patients at admission. In-hospital mortality varied significantly among Brazilian hospitals. Private-funded hospitals and those located in municipalities with a high GDP had a lower mortality. When analyzing ICU-specific characteristics, hospitals with more experienced ICU teams had a reduced mortality.

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.

Prezado editor, Li com interesse o artigo publicado por Costa et al.,1 O uso de estatinas na proteção cardiometabólica promovida por treinamento físico de intensidade moderada em ambiente aquático, pouco tem sido estudado principalmente sob o aspecto clínico. No entanto, como é descrito por Costa et al.,1 o treinamento de força em ambiente aquático aliado ao uso de estatinas tem sido um incremento efetivo por promover adaptações metabólicas e redução dos níveis lipídicos. Os preditores prognósticos associados ao risco de [...] Prezado editor, Li com interesse o artigo publicado por Costa et al.,1 O uso de estatinas na proteção cardiometabólica promovida por treinamento físico de intensidade moderada em ambiente aquático, pouco tem sido estudado principalmente sob o aspecto clínico. No entanto, como é descrito por Costa et al.,1 o treinamento de força em ambiente aquático aliado ao uso de estatinas tem sido um incremento efetivo por promover adaptações metabólicas e redução dos níveis lipídicos. Os preditores prognósticos associados ao risco de

Around 5% of coronavirus disease 2019 (COVID‐19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to describe the clinical characteristics and in‐hospital outcomes of COVID‐19 patients with ARDS refractory to lung‐protective ventilation and prone positioning on ECMO support, as well as to review the available literature on ECMO use and COVID‐19 patients’ outcome. Patients from this case series were selected from the Brazilian COVID‐19 Registry. From the 7646 patients included in the registry, only eight received ECMO support (0.1%), in four hospitals. The median age of the entire sample was 59 (interquartile range 54.2–64.4) years old and 87.5% were male. Hypertension (50.0%), diabetes mellitus (50.0%) and obesity (37.5%) were the most frequent comorbidities. The indications for ECMO were PaO₂/FiO₂ ratio 2/FiO₂ ratio <60 mm Hg for more than 3 h. The mortality rate was 87.5%. In conclusion, in this case series of COVID‐19 patients with ARDS refractory to conventional therapy who received ECMO support, a very high mortality was observed. Our findings are not different from previous studies including a small number of patients; however, there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for improvement.

Chagas disease (CD) continues to be a major public health burden in Latina America. Information on the interplay between COVID-19 and CD is lacking. Our aim was to assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients. Consecutive patients with confirmed COVID-19 were included from March to September 2020. Genetic matching for sex, age, hypertension, diabetes mellitus and hospital was performed in a 4:1 ratio. Of the 7018 patients who had confirmed COVID-19, 31 patients with CD and 124 matched controls were included (median age 72 (64–80) years-old, 44.5% were male). At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (p < 0.05). C-reactive protein levels were lower in CD patients compared with the controls (55.5 [35.7, 85.0] vs. 94.3 [50.7, 167.5] mg/dL). In-hospital management, outcomes and complications were similar between the groups. In this large Brazilian COVID-19 Registry, CD patients had a higher prevalence of atrial fibrillation and chronic heart failure compared with non-CD controls, with no differences in-hospital outcomes. The lower C-reactive protein levels in CD patients require further investigation.

Background: Underlying comorbidities have been widely associated with a worse prognosis for COVID-19 patients, since viral infections could act as triggers for worsening of chronic diseases. Although Chagas disease (CD) is endemic in Latin America, it has been recognized that the disease is now a worldwide concern. Information on the interplay between COVID-19 and CDis lacking. Purpose: To assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients. Methods: Patients with COVID-19 diagnosis were selected from the Brazilian COVID-19 Registry, a prospective multicenter cohort, from March to September, 2020. CD diagnosis was based on hospital record at the time of admission. Study data were collected by trained hospital staff using Research Electronic Data Capture (REDCap) tools. Genetic matching for sex, age, hypertension, DM and hospital was performed in a 4:1 ratio. Results: Of the 7,018 patients who had confirmed infection with SARS-CoV-2 in the registry, 31 patients with CD and 124 matched controls were included. Overall, the median age was 72 (64.-80) years-old and 44.5% were male. At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (p<0.05 for both). C-reactive protein levels were lower in CD patients compared with the controls (55.5 [35.7, 85.0] vs. 94.3 [50.7, 167.5] mg/dL). Seventy-two (46.5%) patients required admission to the intensive care unit. In-hospital management, outcomes and complications were similar between the groups (Table 1). Conclusions: In this large Brazilian COVID-19 Registry, CD patients had a higher prevalence of atrial fibrillation and chronic heart failure compared with non-CD controls, with no differences in-hospital outcomes. The lower C-reactive protein levels in CD patients require further investigation. Funding Acknowledgement: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported in part by Minas Gerais State Agency for Research and Development (Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG) [grant number APQ-00208-20], National Institute of Science and Technology for Health Technology Assessment (Instituto de Avaliação de Tecnologias em Saúde – IATS)/ National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnolόgico - CNPq) [grant number 465518/2014-1], Table 1. Clinical outcomes

Around 5% of coronavirus disease 2019 (COVID-19) patients develop critical disease, with severe pneumonia and acute respiratory distress syndrome (ARDS). In these cases, extracorporeal membrane oxygenation (ECMO) may be considered when conventional therapy fails. This study aimed to assess the clinical characteristics and in-hospital outcomes of COVID-19 patients with ARDS refractory to standard lung-protective ventilation and pronation treated with ECMO support and to compare them to patients who did not receive ECMO. Patients were selected from the Brazilian COVID-19 Registry. At the moment of the analysis, 7,646 patients were introduced in the registry, eight of those received ECMO support (0.1%). The convenience sample of patients submitted to ECMO was compared to control patients selected by genetic matching for gender, age, comorbidities, pronation, ARDS and hospital, in a 5:1 ratio. From the 48 patients included in the study, eight received ECMO and 40 were matched controls. There were no significant differences in demographic, clinical and laboratory characteristics. Mortality was higher in the ECMO group (n = 7; 87.5%) when compared with controls (n = 17; 42.5%), (p=0.048). In conclusion, COVID 19 patients with ARDS refractory to conventional therapy who received ECMO support had worse outcomes to patients who did not receive ECMO. Our findings are not different from previous studies including a small number of patients, however there is a huge difference from Extracorporeal Life Support Organization results, which encourages us to keep looking for our best excellence.

Objective: Chagas disease (CD) continues to be a major public health burden in Latina America, where co-infection with SARS-CoV-2 can occur. However, information on the interplay between COVID-19 and Chagas disease is lacking. Our aim was to assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients. Methods: Patients with COVID-19 diagnosis were selected from the Brazilian COVID-19 Registry, a prospective multicenter cohort, from March to September, 2020. CD diagnosis was based on hospital record at the time of admission. Study data were collected by trained hospital staff using Research Electronic Data Capture (REDCap) tools. Genetic matching for sex, age, hypertension, DM and hospital was performed in a 4:1 ratio. Results: Of the 7,018 patients who had confirmed infection with SARS-CoV-2 in the registry, 31 patients with CD and 124 matched controls were included. Overall, the median age was 72 (64.-80) years-old and 44.5% were male. At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (pT . cruzi can occur in patients living in areas in which both infections are epidemic. What does this study add?: Despite a higher frequency of chronic heart failure and atrial fibrillation, our findings do not suggest that co-infection with T . cruzi and SARS-CoV-2 worsens in-hospital outcomes. Chagas disease patients were observed to have lower C-reactive protein (CRP) levels. How might this impact on clinical practice?: Given the current circulation of SARS-CoV-2 at high levels and millions of T c ruzi -infected individuals living in Brazil, the risk for co-infections substantially increases. Further studies are needed to investigate why CRP levels were lower in CD patients. We hypothesized that CD patients might have a lower risk of unregulated inflammatory response to COVID-19, as they already have an active chronic inflammatory and immune response response triggered by T . cruzi infection.