Direct Application of 3-Maleimido-PROXYL for Proving Hypoalbuminemia in Cases of SARS-CoV-2 Infection: The Potential Diagnostic Method of Determining Albumin Instability and Oxidized Protein Level in Severe COVID-19.

Oxidative stress and the albumin oxidized form can lead to hypoalbuminemia, which is a predisposing factor for reduced treatment effectiveness and an increased mortality rate in severe COVID-19 patients. The aim of the study is to evaluate the application of free radical 3-Maleimido-PROXYL and SDSL-EPR spectroscopy in the in vitro determination of ox/red HSA in serum samples from patients with SARS-CoV-2 infection. Venous blood was collected from patients intubated (pO2 < 90%) with a positive PCR test for SARS-CoV-2 and controls. At the 120th minute after the incubation of the serum samples from both groups with the 3-Maleimido-PROXYL, the EPR measurement was started. The high levels of free radicals were determined through the nitroxide radical TEMPOL, which probably led to increased oxidation of HSA and hypoalbuminemia in severe COVID-19. The double-integrated spectra of 3-Maleimido-PROXYL radical showed a low degree of connectivity due to high levels of oxidized albumin in COVID-19 patients. The low concentrations of reduced albumin in serum samples partially inhibit spin-label rotation, with Amax values and ΔH0 spectral parameters comparable to those of 3-Maleimido-PROXYL/DMSO. Based on the obtained results, we suggest that the stable nitroxide radical 3-Maleimido-PROXYL can be successfully used as a marker to study oxidized albumin levels in COVID-19.

Prognostic properties of hypoalbuminemia in COVID-19 patients: A systematic review and diagnostic meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) elicits robust inflammatory reaction that may result in a declining albumin serum level. This meta-analysis aimed to evaluate the prognostic properties of hypoalbuminemia for poor prognosis and factors that may influence the relationship. METHOD: A systematic literature search of PubMed was conducted from inception to April 22, 2021. The main exposure was albumin level below normal range-defined by the included studies. The outcome of interest was composite poor outcome that comprises of mortality, severity, and the requirement of mechanical ventilation or intensive care unit. RESULTS: There were 6200 patients from 19 studies. Meta-analysis showed that hypoalbuminemia was associated with composite poor outcome (OR 6.97 (95% CI 4.20-11.55), p < 0.001; I2 = 91.3%, p < 0.001). Meta-regression analysis showed that age (p = 0.44), gender (p = 0.76), HT (p = 0.97), DM (p = 0.40), CKD (p = 0.65), liver disease (p = 0.72), and malignancy (p = 0.84) did not affect the association. Subgroup analysis showed that hypoalbuminemia increased mortality (OR 6.26 (95% CI 3.26-12.04), p < 0.001; I2 = 69.6%, p < 0.01) and severity of the disease (OR 7.32 (95%CI 3.94-13.59), p < 0.001; I2 = 92.5%, p < 0.01). Pooled diagnostic analysis of hypoalbuminemia yielded a sensitivity of 0.63 (95% CI 0.52-0.72), specificity of 0.81 (95% CI 0.73-0.87), and AUC of 0.77. The probability of poor outcome was 70% in patients with hypoalbuminemia and 24% in patients with normal albumin level. CONCLUSION: Hypoalbuminemia was associated with poor prognosis in COVID-19 patients.

Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19.

BACKGROUND: Research surrounding COVID-19 (coronavirus disease 2019) is rapidly increasing, including the study of biomarkers for predicting outcomes. There is little data examining the correlation between serum albumin levels and COVID-19 disease severity. The purpose of this study is to evaluate whether admission albumin levels reliably predict outcomes in COVID-19 patients. METHODS: We retrospectively reviewed 181 patients from two hospitals who had COVID-19 pneumonia confirmed by polymerase chain reaction (PCR) testing and radiologic imaging, who were hospitalized between March and July 2020. We recorded demographics, COVID-19 testing techniques, and day of admission labs. The outcomes recorded included the following: venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, discharge with new or higher home oxygen supplementation, readmission within 90 days, in-hospital mortality, and total adverse events. A multivariate modified Poisson regression analysis was then performed to determine significant predictors for increased adverse events in patients with COVID-19 pneumonia. RESULTS: A total of 109 patients (60.2%) had hypoalbuminemia (albumin level < 3.3 g/dL). Patients with higher albumin levels on admission had a 72% decreased risk of developing venous thromboembolism (adjusted relative risk [RR]:0.28, 95% confidence interval [CI]:0.14-0.53, p<0.001) for every 1 g/dL increase of albumin. Moreover, higher albumin levels on admission were associated with a lower risk of developing ARDS (adjusted RR:0.73, 95% CI:0.55-0.98, p = 0.033), admission to the ICU (adjusted RR:0.64, 95% CI:0.45-0.93, p = 0.019), and were less likely to be readmitted within 90 days (adjusted RR:0.37, 95% CI:0.17-0.81, p = 0.012). Furthermore, higher albumin levels were associated with fewer total adverse events (adjusted RR:0.65, 95% CI:0.52-0.80, p<0.001). CONCLUSIONS: Admission serum albumin levels appear to be a predictive biomarker for outcomes in COVID-19 patients. We found that higher albumin levels on admission were associated with significantly fewer adverse outcomes, including less VTE events, ARDS development, ICU admissions, and readmissions within 90 days. Screening patients may lead to early identification of patients at risk for developing in-hospital complications and improve optimization and preventative efforts in this cohort.

DVT incidence and risk factors in critically ill patients with COVID-19.

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55-71) years old and 5 (4-6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35-56%). Proximal DVT was recognized in 9% (95% CI 3-15%) of the patients, while 46% (95% CI 35-56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06-0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38-3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03-1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.