NOT ENERGY, BUT A BETTER PROVISION OF PROTEIN IN ICU SEEMS TO BE CRITICAL FOR THE SURVIVAL OF PATIENTS WITH COVID-19

Background and aims: Although recent data suggests that adequate delivery of nutritional therapy impacts positively on the outcomes, critically ill patients often suffer from underfeeding due to several factors. Causes for low provision of nutrients include fasting, gastrointestinal dysfunction, the conditions imposed by the illness, as observed in COVID-19, poor content of protein in the enteral formulas, and the delivery of non-nutritional calories (i.e., propofol). This study aimed to verify an association between mortality and the energy and protein provided to critically ill patients, including a subgroup affected by the SARS-CoV- 2. Methods: First, general mortality in the ICU was evaluated using logistic regression in patients receiving oral, enteral, and parenteral Nutritional Therapy (NT), according to the rate of NT compliance (calculated by the percentage of days that the nutrition support was offered properly in relation to the total number of days of hospitalization, according to the type of therapy). Also, a subgroup of patients with SARS-CoV-2 infection confirmed by RTPCR, with at least 7 days of hospitalization in the intensive care unit (ICU), requiring MV, and exclusively fed by enteral nutrition were evaluated according to the outcomes discharge or death. Age, gender, Simplified Acute Physiology Score III (SAPS3), ICU length of stay (LOS), days on MV, outcomes (discharge or death), and daily energy and protein provision were collected from electronic medical records. Cox regression analyses and Kaplan Meyer curves were used in statistical analysis of the COVID-19 subgroup. Results: 180 patients (72±15 years, 50% men) were enrolled. The mean LOS was 17±11 days. Nutritional risk was present in 161 patients (89%) and malnutrition in 19 (11%). One hundred and seven patients (59%) were discharged, and 73 (40%) died. The NT compliance rate (%) was negatively associated with the overall mortality in the ICU [OR: 0.96 (95% CI 0.94-0.98), p=0.001], even when the model was adjusted by age, nutritional status, LOS, days on MV, and type of NT. Patients with a lower NT compliance rate have significantly higher mortality (p<0.001). Fifty-two patients (66 ± 13 years;54% women) were enrolled in the COVID- 19 subgroup. The mean LOS was 17.8 ± 9.8 days, and SAPS3 was 79 ± 15;all patients needed MV (mean of days was 16 ± 9). Most patients (73%) died. Hazard Ratios (HR) for protein supply, delivered according to patients' ideal body weight (IBW), showed that a protein intake >0.8 g/IBW/day was associated with significantly lower mortality (HR 0.3 (95% CI 0.1-0.7), p=0.04). Energy intake was not related to survival (HR 0.94, (95% CI 0.9-1.0, p=0.09), being the same observed for other variables, such age, days on MV, and SAPS3. Conclusion: protein provision is suggested to be related to reduced mortality in ICU patients with COVID-19.

Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.

Lung ultrasound score predicts outcomes in COVID-19 patients admitted to the emergency department

RATIONALE During the COVID-19 pandemic, creating tools to assess disease severity is one of the most important aspects of reducing the burden on emergency departments. Lung ultrasound has a high accuracy for the diagnosis of pulmonary diseases;however, there are few prospective studies demonstrating that lung ultrasound can predict outcomes in COVID-19 patients. We hypothesized that lung ultrasound score (LUS) at hospital admission could predict outcomes of COVID-19 patients. METHODS This is a prospective cohort study conducted from 14 March through 6 May 2020 in the emergency department (ED) of an urban, academic, level I trauma center. Patients aged 18 years and older and admitted to the ED with confirmed COVID-19 were considered eligible. Emergency physicians performed lung ultrasounds and calculated LUS, which was tested for correlation with outcomes. This protocol was approved by the local Ethics Committee number 3.990.817 (CAAE: 30417520.0.0000.0068). RESULTS The primary endpoint was death from any cause. The secondary endpoints were ICU admission and endotracheal intubation for respiratory failure. Among 180 patients with confirmed COVID-19 who were enrolled (mean age, 60 years;105 male), the average LUS was 18.7 ± 6.8. LUS correlated with findings from chest CT and could predict the estimated extent of parenchymal involvement (mean LUS with < 50% involvement on chest CT, 15±6.7 vs. 21±6.0 with >50% involvement, p<0.001), death (AUC 0.72, OR 1.13, 95% CI 1.07 to 1.21;p < 0.001), endotracheal intubation (AUC 0.76, OR 1.17, 95% CI 1.09 to 1.26;p < 0.001), and ICU admission (AUC: 0.71, OR 1.14, 95% CI 1.07 to 1.21;p < 0.001). CONCLUSION In this study, LUS was a good predictor of death, ICU admission, and endotracheal intubation in patients with COVID-19 admitted in ED. The study provides support for further research, ideally combining clinical, laboratory, and imaging parameters, to estimate the risk of poor outcomes from COVID-19 infection.

Community-acquired Pneumonia Severity Assessment Tools in Patients Hospitalized with COVID-19: a Validation and Clinical Applicability Study

OBJECTIVE: To externally validate community acquired pneumonia (CAP) tools on patients hospitalized with COVID-19 pneumonia from two distinct countries, and compare its performance to recently developed COVID-19 mortality risk stratification tools. METHODS: We evaluated 11 risk stratification scores in a binational retrospective cohort of patients hospitalized with COVID-19 pneumonia in Sao Paulo and Barcelona: Pneumonia Severity Index (PSI), CURB, CURB-65, qSOFA, Infectious Disease Society of America and American Thoracic Society Minor Criteria, REA-ICU, SCAP, SMART-COP, CALL, COVID GRAM and 4C. The primary and secondary outcomes were 30-day in-hospital mortality and seven-day intensive-care unit (ICU) admission respectively. We compared their predictive performance using the area under the ROC curve (AUROC), sensitivity, specificity, likelihood ratios, calibration plots and decision curve analysis. RESULTS: Of 1363 patients, the mean (SD) age was 61 (16) years. The 30-day in-hospital mortality rate was 24.6% (228/925) in Sao Paulo and 21.0% (92/438) in Barcelona. For in-hospital mortality, we found higher AUROCs for PSI (0.79, 95%CI 0.77-0.82), 4C (0.78, 95%CI 0.75-0.81), COVID GRAM (0.77, 95%CI 0.75-0.80), and CURB-65 (0.74 95%CI 0.72-0.77). Results were similar for both countries. For most 1-20% threshold range in decision curve analysis, PSI would avoid a higher number of unnecessary interventions, followed by the 4C score. All scores had poor performance (AUROC<0.65) for seven-day ICU admission. CONCLUSIONS: Recent clinical COVID-19 assessment scores had comparable performance to standard pneumonia assessment tools. Because it is expected that new scores outperform older ones during development, external validation studies are needed before recommending their use.