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Serum albumin levels and severe forms of COVID-19

Posted by S.Arques on 17 Mar 2021 at 11:23 GMT

We are currently facing a Covid-19 pandemic worldwide. While the majority of clinical forms are mild, some are severe, leading to admission to intensive care units and even to death. The identification of potentially modifiable aggravating factors therefore appears crucial in this setting.
Numerous observational studies have highlighted the high prevalence of hypoalbuminemia in patients with Covid-19, particularly in its most severe forms.1,2 These studies also report that hypoalbuminemia is a powerful predictor of death in patients with Covid-19, even after adjustment in multivariate analysis.1,2 This prognostic relevance probably refers primarily to malnutrition, inflammation, liver dysfunction and comorbidities. However, serum albumin has various physiological functions, in particular an anti-inflammatory, antioxidant, anti-platelet aggregation and anticoagulant activity.3 It also has a binding function for many substances, drugs and antibiotics. In addition, it exerts a plasma colloid osmotic pressure action that prevents the formation of pulmonary edema and congestion of peripheral tissues and organs.3 Hypoalbuminemia, especially if severe, may contribute to the multi-organ failure through the exacerbation of inflammation, oxidative stress, thrombotic events and peripheral congestion, to the worsening of cardiorespiratory distress by pulmonary edema, especially in patients with heart failure, and thus contribute to the adverse outcome of severe forms of Covid-19.
It is unclear whether correction of hypoalbuminemia in critically ill patients confers benefit. The SAFE study is the largest randomized controlled trial to have addressed the safety of albumin transfusion in this setting.4 Albumin and saline infusion provided similar outcome at 1 month, however, patients were eligible for this study provided that fluid administration was required to maintain or increase intravascular volume regardless of serum albumin concentration. Of note, half patients with severe hypoalbuminemia who benefited from albumin transfusion did not attain a concentration >3 g/dl, while a meta-analysis has suggested that attaining a serum albumin concentration >3 g/dl during albumin transfusion may reduce the rate of adverse event in critically ill patients with severe hypoalbuminemia.5 Analysis of subgroups of the SAFE trial suggests that the benefits of albumin transfusion may depend on the underlying disease. Albumin transfusion is currently not recommended as first line fluid resuscitation in critically ill patient with severe sepsis, while albumin infusion may confer survival benefits in this setting.6 Therefore, albumin replacement for correcting severe hypoalbuminemia, whether or not associated with furosemide, should be a clinically relevant therapeutic option in patients with severe forms of Covid-19.
1. Violi F, Cangemi R, Romiti GF, Ceccarelli G, Oliva A, Alessandri F, Pirro M, Pignatelli P, Lichtner M, Carraro A, Cipollone F, D’Ardes D, Pugliese F, Mastroianni CM. Is albumin predictor of mortality in COVID-19? Antioxid Redox Signal 2020 Jun 22. Doi: 10.1089/ars.2020.8142. Online ahead of print.
2. Aloisio E, Chibireva M, Serafini L, Pasqualetti S, Falvella FS, Dolci A, Panteghini M. A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity. Arch Pathol Lab Med 2020;144:1457-64.
3. Arques S. Human serum albumin in cardiovascular diseases. Eur J Intern Med 2018; 52: 8-12.
4. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R, SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350: 2247-56.
5. Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg 2003; 237: 319-34.
6. Wiedermann CJ, Joannidis M. Albumin replacement in severe sepsis or septic shock. N Engl J Med 2014; 371:83.

No competing interests declared.