Serum Albumin Kinetics and Mortality in Adult Covid-19 Patients Who Underwent Intensive Care

ABSTRACT

INTRODUCTION: Serum albumin (ALB) is inversely associated with COVID-19 severity through an unclear mechanism. We addressed this gap using machine learning to identify traits exhibiting explanatory variance (EV%) in mortality risk within 12h of admission versus near end of hospitalization in the context of hypoalbuminemia. METHOD(S) Data were extracted under IRB exemption from medical records of COVID-19 patients at least 18 years old in the ICU with at least two ALB measures from March 2020 through September 2021. ALB, COVID-19 inflammation and injury traits were characterized across hospitalization. Hypoalbuminemia present on admission (POA) was defined as ALB < 3.2 g/dL. Traits associated with mortality were controlled for age, sex, COVID-19 directed treatment and the four COVID surges. Bootstrap Forest (BF) evaluated EV% of traits in mortality. Continuous data were compared using KruskalWallis. Discrete data were compared with chi-squared test. RESULT(S) Among 878 patients, 631 (72%) vs. 247 (28%) POA respectively with ALB < 3.2g/dL vs. >3.2g/ dL. Median age 68(57,77) years distributed across 64% males with 75% Whites, 10% Blacks and 15% other races exhibiting hypertension (53%), coagulopathy (28%), chronic pulmonary disease (22%) and heart failure (22%). Excess comorbidity associated with hypoalbuminemia included obesity (48% vs. 38%, p=.004), anemias (42% vs. 28%, p<.0001), and diabetes (39% vs. 32%, p=.03). Respective hypoalbuminemia near end of hospitalization increased to 97% (p<.0001) and 84% (p<.0001) with hospital mortality of 51% vs. 31% (p=<.0001). Associated ALB declines were 0.5(0.1, 1.0) vs. 1.0 (0.6, 1.0) g/dL. BF modeling (RSquared=0.69) identified POA traits EV% including CRP (21%), AST/SGOT (11%), proBNP (9%), WBC (9%), and ferritin (9%) among others. BF modeling (RSquared=0.84) identified near end visit traits EV% including WBC (31%), CRP (13%), platelet (12%), and ANC (11%) among others. CONCLUSION(S) The EV% of CRP at presentation corroborates an inverse relationship with ALB suggesting acute phase signaling may evoke hypoalbuminemia. Specifically, increased endothelial permeability allowing ALB extravasation as evidenced by proBNP EV%. Secondary etiology may derive from inhibited albumin synthesis secondary to liver injury as suggested by AST/SGOT at presentation and visit end.