Ally in Fighting Covid-19: Magnitude of Albumin Decline and Lymphopenia (Ally) Predict Progression to Critical Disease

Abstract

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was −0.08 g/dL/day (95% CI −0.11 to −0.04; p<0.001) or four times faster, in those who progressed compared with those who did not progress. A model of Δ albumin combined with lymphocyte percentage predicting progression to critical disease was validated in 60 separate patients (sensitivity, 0.70; specificity, 0.74). ALLY (delta albumin and lymphocyte percentage) is a simple tool to identify patients with COVID-19 at higher risk of disease progression when: (1) a 0.9 g/dL or greater albumin drop from baseline within 5 days of admission or (2) baseline lymphocyte of ≤10% is observed. The ALLY tool identified >70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.

Correlation of Rate of Serum Albumin Decline with other Acute Phase Reactants and Effect of Current Treatment Options on Serum Albumin Level in Covid-19

“… 3 The study could not correlate the magnitude and the rate of albumin change with inflammatory biomarkers such as C-reactive protein (CRP) or IL-6 which were not consistently available over the course of admission. 1 ⁠⁠ This means that the study could not make a conclusion that the albumin decline of 0.9 g/dL or greater within 5 days of admission was solely due to COVID-19-induced inflammatory state. Correlating the albumin level with CRP and IL-6 would have helped to rule out the effect of comorbidities and confounders which might have affected albumin levels.…”

“…First, the study used a comorbidity score to calculate the number of comorbidities present at admission out of asthma, coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus, hypertension, cancer, history of renal disease, and smoking. 1 ⁠ Liver disease has not been considered in the comorbidity scale, which can greatly influence the albumin level at any given time and the rate of its decline.…”

“…Third, the study mentions that the analysis was performed at the time when steroids were discouraged by the WHO guidelines, 1 so considering an albumin drop of 0.9 g/dL or greater within 5 days of admission as a factor for higher risk of disease progression might not be correct at present due to the availability of various treatment options such as corticosteroids and IL-6 inhibitors that suppress cytokine storm. 4 ⁠⁠ The effect of such drugs on albumin level in patients with COVID-19 needs to be investigated as they might have an effect on the rate of albumin decline.…”

Dynamic Albumin Values as Clinical Surrogate for Covid-19 Therapeutics

“…We posited that albumin levels fall dynamically due to the hyperinflammatory pathophysiology of COVID-19, with attendant capillary leak. 2 We are delighted that the author of the above letter shares our burning question: does the dynamic fall of serum albumin track the hyperinflammatory markers of C-reactive protein, ferritin, and interleukin 6 (IL-6), and do immunomodulators such as glucocorticoids or anti-IL-6 receptor or anti-IL-6 cytokine monoclonal antibody therapies reverse this? This is an important avenue for future investigation.…”

“…The closing of our original manuscript rings true today: ‘Finally, we propose that the variables of interest identified in our risk model should be included as risk markers in future treatment studies for COVID-19.’ 2 …”