1. Immunology and Inflammation
  2. Medicine
Download icon

Cytokine ranking via mutual information algorithm correlates cytokine profiles with presenting disease severity in patients infected with SARS-CoV-2

  1. Kelsey E Huntington
  2. Anna D Louie
  3. Chun Geun Lee
  4. Jack A Elias
  5. Eric A Ross
  6. Wafik S El-Deiry  Is a corresponding author
  1. Brown Experimentalists Against COVID-19 (BEACON) Group, Brown University, United States
  2. Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Warren Alpert Medical School, Brown University, United States
  3. The Joint Program in Cancer Biology, Brown University and Lifespan Health System, United States
  4. Cancer Center at Brown University, Warren Alpert Medical School, Brown University, United States
  5. Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, United States
  6. Pathobiology Graduate Program, Warren Alpert Medical School, Brown University, United States
  7. Department of Molecular Microbiology and Immunology, Brown University, United States
  8. Department of Surgery, Lifespan Health System and Warren Alpert Medical School, Brown University, United States
  9. Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Temple University Health System, United States
  10. Hematology-Oncology Division, Department of Medicine, Lifespan Health System and Warren Alpert Medical School, Brown University, United States
Short Report
Cite this article as: eLife 2021;10:e64958 doi: 10.7554/eLife.64958
4 figures, 1 table and 2 additional files


Mutual information COVID Severity Score (CSS) relevancy matrix.

(A) Comprehensive matrix of relevancy to CSS of all variables assessed by mutual information algorithm, relevancy scores computed for not-yet selected variables are shown in each column, and variables are ordered to place maximum local scores on the diagonal, yielding a list in decreasing order from the upper left of variable relevancy. Warmer colors indicate higher relevancy, while cooler colors indicate higher redundancy. (B) COVID Severity Score Table with breakdown of categories as well as sample size per category.

Age, macrophage colony-stimulating factor (M-CSF), and chest x-ray are the most predictive variables for COVID Severity Score (CSS).

(A) The y-axis is CSS, and the x-axis is age in years with points colored by chest x-ray status. (B) The y-axis is M-CSF concentration in pg/mL, and the x-axis is age in years, with points colored based on CSS. See individual legends below graphs. (C) Receiver operating characteristic (ROC) curve predicting CSS 4–5 using age, M-CSF, IP-10, IL-18, and IL-1RA, and ROC curve predicting CSS 4–5 using only age.

Violin plot representations of cytokine expression levels ordered by COVID Severity Score (CSS).

Cytokines ordered by row from upper left corner based on mutual information relevancy matrix (upper left being most relevant and lower right being least relevant). The x-axis is CSS, and the y-axis is analyte concentration in pg/mL. One-way ANOVA F values and p values are listed on each plot. Source code 1. R code with sections to apply the varrank package to the source data, create a receiver operating characteristic curve, and calculate analysis of variance for each cytokine.

Figure 3—source data 1

Raw data.

Source Data Table 1. Mutual algorithm criteria table. *Documented obesity or overweight for height < 99th percentile. Source Data Table 2. Patient information.

Author response image 1


Key resources table
Reagent type
(species) or resource
DesignationSource or referenceIdentifiersAdditional
Biological samples (Human)Human plasmaLifespan Brown COVID-19 BiobankSee data table48 unique patients
Biological samples (Human)Human plasmaLee BioSolutions991–58-PS24 unique patients
Commercial assay or kitMILLIPLEX MAP Human Immunology Multiplex AssayMillipore Sigma15-Plex # HCYTA-60K
Software, algorithmRR Project for Statistical ComputingRRID:SCR_001905
OtherLuminex 100/200 System assay platformThermo Fisher Scientifichttps://www.luminexcorp.com/luminex-100200

Additional files

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)