key: cord-0782641-gvzvvrfx
authors: Huang, Jiaofeng; Cheng, Aiguo; Kumar, Rahul; Fang, Yingying; Chen, Gongping; Zhu, Yueyong; Lin, Su
title: Hypoalbuminemia predicts the outcome of COVID‐19 independent of age and co‐morbidity
date: 2020-05-25
journal: J Med Virol
DOI: 10.1002/jmv.26003
sha: c633117aad883b39fdb248dce191f8d34483d246
doc_id: 782641
cord_uid: gvzvvrfx

The coronavirus disease 2019 (COVID‐19) has evolved into a pandemic rapidly. Most of the literature show that the elevated liver enzymes in COVID‐19 are of little clinical significance. Lower albumin level is seen in severe COVID‐19 and is not parallel to the changes in alanine aminotransferase and aspartate aminotransferase levels. We aimed to explore the impact of hypoalbuminemia in COVID‐19. This retrospective cohort study included adult patients with confirmed COVID‐19. The relationship between hypoalbuminemia and death was studied using binary logistic analysis. A total of 299 adult patients were included, 160 (53.5%) were males and the average age was 53.4 ± 16.7 years. The median time from the onset of illness to admission was 3 days (interquartile ranges, 2‐5). Approximately one‐third of the patients had comorbidities. Hypoalbuminemia (<35 g/L) was found in 106 (35.5%) patients. The difference in albumin was considerable between survivors and non‐survivors (37.6 ± 6.2 vs 30.5 ± 4.0, P < .001). Serum albumin level was inversely correlated to white blood cell (r = –.149, P = .01) and neutrophil to lymphocyte ratio (r = −.298, P < .001). Multivariate analysis showed the presence of comorbidities (OR, 6.816; 95% CI, 1.361‐34.133), lymphopenia (OR, 13.130; 95% CI, 1.632‐105.658) and hypoalbuminemia (OR, 6.394; 95% CI, 1.315‐31.092) were independent predictive factors for mortality. In conclusion, hypoalbuminemia is associated with the outcome of COVID‐19. The potential therapeutic value of albumin infusion in COVID‐19 should be further explored at the earliest.

decreased albumin level is common in severe COVID-19, 7,12 but the change in albumin does not parallel the severity of hepatocellular injury in This suggests that there may be mechanisms other than a hepatocellular injury that explains the profound hypoalbuminemia seen in COVID-19. One of the possible mechanisms is the intense systemic inflammation being reported in severe COVID-19. 13 Hypoalbuminemia is common in many inflammatory diseases because increased capillary permeability can result in the escape of albumin to the interstitial space. 14 The role of albumin in the progression of COVID-19 remains unknown. We hypothesized that serum albumin levels at admission might reflect the severity of systemic inflammation and thus can serve as a predictive factor for COVID-19 outcomes.

To address this question, we performed a retrospective study to compare the outcome in patients with or without hypoalbuminemia and to explore the impact of albumin in the prognosis of COVID-19. in the hospital. Those who smoked more than 10 cigarettes/day in the past 30 days were considered as current smokers. 16 Heavy drinking was defined as long-term habitual alcohol consumption, usually longer than 5 years, of more than 40 g/d in males and 20 g/d in females, or a history of binging on alcoholic beverages within the past 2 weeks with a converted alcohol intake > 80 g/d. 17 The comorbidity of interest that was recorded was hypertension, diabetes mellitus (DM), coronary heart disease (CHD), cerebrovascular disease (CVD), chronic obstructive pulmonary disease (COPD), and cancer.

All blood samples were obtained at admission and analyzed by standard methods in the laboratory. The routine hematological and biochemical tests included white blood cell count (WBC), neutrophil count, lymphocyte count, monocyte count, CRP, procalcitonin, erythrocyte sedimentation rate (ESR), d-dimer, fibrinogen, and liver and kidney function tests.

Neutrophil-to-lymphocyte ratio (NLR) value was measured by dividing the neutrophil count by the lymphocyte count.

The normal range value of the serum albumin was 35-55 g/L. Based on the previous research, we defined hypoalbuminemia as albumin less than 35 g/L. 18 The normal range of lymphocyte count was (1-4) × 10 9 /L, thus lymphopenia was defined as lymphocyte count of <1 × 10 9 /L.

Continuous variables were expressed as means ± SD or medians with interquartile ranges (IQRs), according to whether the distribution was normal or skewed. Categorical variables were expressed as percentages.

The Student t test (for variables normally distributed) and Mann-Whitney U test (for variables non-normally distributed) were performed. The difference between categorical variables was examined with the χ 2 test or Fisher's exact test as appropriate. A P-value < .05 was considered statistically significant. Pearson correlation analysis was used to analyze the relationship between albumin and inflammatory indicators. Data management and analysis were performed using R software (R version 3.6.3, R Foundation for Statistical Computing, Vienna, Austria). Approximately one-third of the patients had comorbidities, of which hypertension, DM, CHD, CVD, COPD, and cancer were present in 74 (24.7%), 35 (11.7%), 18 (6.0%), 13 (4.3%), 8 (2.7%) and 9 (3.0%) cases, respectively. A total of 113 patients (37.8%) had been to Wuhan before the illness. The most common symptoms on admission were fever (79.6%) and cough (74.2%), followed by increased phlegm/sputum production (45.2%) and dyspnea (14.0%). Lymphopenia was found in 127 (42.5%) and hypoalbuminemia in 106 (35.5%) patients. Forty-six patients required intensive care unit (ICU) admission and treatment (Table 1) . Note: Continuous variables were expressed as means ± SD or medians with interquartile ranges (IQRs). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CHD, coronary heart disease; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CVD, cerebrovascular disease; DM, diabetes mellitus; ESR, erythrocyte sedimentation rate; ICU, intensive care unit; LDH, lactic dehydrogenase; NLR, neutrophil-to-lymphocyte ratio; WBC, white blood cell count. 

T A B L E

Pearson correlation analysis was used to explore the relationship between albumin and inflammatory indicators. Albumin level was (Table 3 ).

The most important finding of our study is that there is an inverse relationship between the level of albumin and the risk of death in F I G U R E 1 Pearson linear correlation analysis scatter plot is shown. A indicated that the level of albumin and CRP were positively correlated; B indicated that the levels of albumin and NLR were positively correlated HUANG ET AL. In this study, a significant correlation was found between albumin level and inflammatory indicators (CRP, WBC, and NLR). Systemic inflammation is common in severe COVID-19. 13 Inflammation has been shown to cause the escape of serum albumin into interstitial space due to increased capillary permeability, and eventually lead to increased volume distribution of albumin. 14 Thus, our study strongly implies that hypoalbuminemia might due to the systemic inflammation in COVID-19.

Therapeutic efficacy of albumin in sepsis and cirrhosis demonstrates that it can act through a modulatory effect on inflammation and oxidative stress in addition to the plasma volume expansion. 14, 27, 28 Albumin treatment has been shown to improve oxygenation in ARDS by a meta-analysis. 29 As there is no specific treatment for the systemic inflammation in COVID-19 until now, an albumin treatment with low side-effect could be a potential approach. However, the efficacy and safety of albumin in COVID-19 requires to be verified in prospective studies as the majority of severe COVID-19 is elderly with cardiovascular comorbidities.

Our study should be interpreted in light of some limitations. We have reported a single-center experience and data in this retrospective study;

however, the baseline factors in our study is consistent with the presently 

The authors declare that there are no conflict of interests.

JH and SL designed the study and drafted the manuscript. YF, GC, and AC acquisited and did the statistical analysis. RK and AC made a critical revision. YZ and SL did the study supervision.

Ethical approval for the study was obtained from the ethics 

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