Low Serum Albumin Level Strongly Associated with Severe COVID-19

Given that hypoalbuminemia has been associated with critical illness and mortality across numerous clinical settings, and laboratory markers are needed for early recognition of worsening COVID-19 disease, University of Toledo investigators conducted a systematic review and meta-analysis to determine whether there may be an association between hypoalbuminemia and severe COVID-19.

An extensive literature search of PubMed/MEDLINE, Embase, Cochrane and Web of Science was conducted through April 30, 2020. Two independent reviewers performed screening and article data extraction; a total of 11 studies, totaling 910 patients with a mean age of 47.6 ± 8.2 years, were included. Severe COVID-19 was defined as respiratory distress (with either rate ≥30/minute, oxygen saturation ≤93 percent at rest and/or PaO2/FIO2 ≤300 mmHg), ICU admission and/or death. Hypoalbuminemia was reported based on reference laboratory parameters for each cited study.

The weighted mean serum albumin on admission was 3.50 g/dL (95% confidence interval [CI] 3.26-3.74 g/dL) and 4.05 g/dL (95% CI 3.82-4.27 g/dL) in the severe and nonsevere COVID-19 groups, respectively. This was statistically significant with a mean difference (MD) of -0.56 g/dL, 95% CI -0.69 to -0.42 g/dL, p < 0.001. The results were consistent on subgroup analysis of eight studies that defined severe COVID-19 based on a respiratory distress definition (MD -0.58 g/dL, 95% CI -0.78 to -0.37 g/dL, p < 0.001). Four of these studies that specifically assessed hypoalbuminemia status in relation to severe COVID-19 found a very strong association, with an odds ratio of 12.6 (95% CI 7.5-21.1, p <0.001).

The study authors acknowledged it is difficult to assess whether severe COVID-19 resulted in hypoalbuminemia, or the opposite. Whether hypoalbuminemia should be corrected or not “needs further evaluation in future studies,” they added.