Physico-chemical characterization of acid base disorders in patients with COVID-19: A cohort study.

BACKGROUND: Acid-base imbalance has been poorly described in patients with coronavirus disease 2019 (COVID-19). Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques. In a cohort of critically ill COVID-19 patients, we looked for an association between metabolic acidosis surrogates and worse clinical outcomes, such as mortality, renal dialysis, and length of hospital stay. AIM: To describe the acid-base disorders of critically ill COVID-19 patients using Stewart's approach, associating its variables with poor outcomes. METHODS: This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan. Laboratory and clinical data were obtained from electronic records. Categorical variables were compared using Fisher's exact test. Continuous data were presented as median and interquartile range. The Mann-Whitney U test was used for comparisons. RESULTS: In total, 211 patients were analyzed. The mortality rate was 13.7%. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pondus hydrogenii. Of those presenting with acidosis, most had a low apparent strong ion difference (SID) (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61.0%) had respiratory origin. The non-survivors were older, had more comorbidities, and had higher Charlson's and simplified acute physiology score 3. We did not find severe acid-base imbalance in this population. The analyzed Stewart's variables (effective SID, apparent SID, and strong ion gap and the effect of albumin, lactate, phosphorus, and chloride) were not different between the groups. CONCLUSION: Alkalemia is prevalent in COVID-19 patients. Although we did not find an association between acid-base variables and mortality, the use of Stewart's methodology may provide insights into this severe disease.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial.

SARS-CoV-2 and its different variants caused a "wave and wave" pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI - 0.74 [- 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI - 0.28 [0.1-0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. METHODS: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). DISCUSSION: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

Evaluation of urine SARS-COV-2 RT-PCR as a predictor of acute kidney injury and disease severity in patients with critical COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began as an outbreak in Wuhan, China and has spread rapidly across the globe. Although most infections are mild, patients with severe and critical COVID-19 infections face deterioration of respiratory function and may also have extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart, and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material using reverse-transcription polymerase chain reaction in urine samples obtained from patients with COVID-19 receiving critical care. Among 51 included patients, we found higher serum creatinine levels, a longer hospital stay, and more frequent need for dialysis in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.

Inverse association between serum creatinine and mortality in acute kidney injury.

INTRODUCTION: Sepsis is a leading precipitant of Acute Kidney Injury (AKI) in intensive care unit (ICU) patients, and is associated with a high mortality rate. OBJECTIVE: We aimed to evaluate the risk factors for dialysis and mortality in a cohort of AKI patients of predominantly septic etiology. METHODS: Adult patients from an ICU for whom nephrology consultation was requested were included. End-stage chronic renal failure and kidney transplant patients were excluded. RESULTS: 114 patients were followed. Most had sepsis (84%), AKIN stage 3 (69%) and oliguria (62%) at first consultation. Dialysis was performed in 66% and overall mortality was 70%. Median serum creatinine in survivors and non-survivors was 3.95 mg/dl (2.63 - 5.28) and 2.75 mg/dl (1.81 - 3.69), respectively. In the multivariable models, oliguria and serum urea were positively associated with dialysis; otherwise, a lower serum creatinine at first consultation was independently associated with higher mortality. CONCLUSION: In a cohort of septic AKI, oliguria and serum urea were the main indications for dialysis. We also described an inverse association between serum creatinine and mortality. Potential explanations for this finding include: delay in diagnosis, fluid overload with hemodilution of serum creatinine or poor nutritional status. This finding may also help to explain the low discriminative power of general severity scores - that assign higher risks to higher creatinine levels - in septic AKI patients.

Septic versus non-septic acute kidney injury in critically ill patients: characteristics and clinical outcomes.

OBJECTIVE: This study aimed to describe and compare the characteristics and clinical outcomes of patients with septic and non-septic acute kidney injury. METHODS: This study evaluated an open cohort of 117 critically ill patients with acute kidney injury who were consecutively admitted to an intensive care unit, excluding patients with a history of advanced-stage chronic kidney disease, kidney transplantation, hospitalization or death in a period shorter than 24 hours. The presence of sepsis and in-hospital death were the exposure and primary variables in this study, respectively. A confounding analysis was performed using logistic regression. RESULTS: No significant differences were found between the mean ages of the groups with septic and non-septic acute kidney injury [65.30±21.27 years versus 66.35±12.82 years, respectively; p=0.75]. In the septic and non-septic acute kidney injury groups, a predominance of females (57.4% versus 52.4%, respectively; p=0.49) and Afro-descendants (81.5% versus 76.2%, respectively; p=0.49) was observed. Compared with the non-septic patients, the patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II score [21.73±7.26 versus 15.75±5.98; p<0.001)] and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart failure (p<0.001) were more common in the non-septic patients. Septic acute kidney injury was associated with a greater number of patients who required dialysis (p=0.001) and a greater number of deaths (p<0.001); however, renal function recovery was more common in this group (p=0.01). Sepsis (OR: 3.88; 95%CI: 1.51-10.00) and an Acute Physiology and Chronic Health Evaluation II score >18.5 (OR: 9.77; 95%CI: 3.73-25.58) were associated with death in the multivariate analysis. CONCLUSION: Sepsis was an independent predictor of death. Significant differences were found between the characteristics and clinical outcomes of patients with septic versus non-septic acute kidney injury.

Comparison of the RIFLE, AKIN and KDIGO criteria to predict mortality in critically ill patients.

OBJECTIVE: Acute kidney injury is a common complication in critically ill patients, and the RIFLE, AKIN and KDIGO criteria are used to classify these patients. The present study's aim was to compare these criteria as predictors of mortality in critically ill patients. METHODS: Prospective cohort study using medical records as the source of data. All patients admitted to the intensive care unit were included. The exclusion criteria were hospitalization for less than 24 hours and death. Patients were followed until discharge or death. Student's t test, chi-squared analysis, a multivariate logistic regression and ROC curves were used for the data analysis. RESULTS: The mean patient age was 64 years old, and the majority of patients were women of African descent. According to RIFLE, the mortality rates were 17.74%, 22.58%, 24.19% and 35.48% for patients without acute kidney injury (AKI) in stages of Risk, Injury and Failure, respectively. For AKIN, the mortality rates were 17.74%, 29.03%, 12.90% and 40.32% for patients without AKI and at stage I, stage II and stage III, respectively. For KDIGO 2012, the mortality rates were 17.74%, 29.03%, 11.29% and 41.94% for patients without AKI and at stage I, stage II and stage III, respectively. All three classification systems showed similar ROC curves for mortality. CONCLUSION: The RIFLE, AKIN and KDIGO criteria were good tools for predicting mortality in critically ill patients with no significant difference between them.