Figure 7. Quantification of biomarkers in BAL fluid from patients with severe COVID-19 or influenza, stratified by the timing of a bacterial coinfection.

Multiplex and ELISA technology was used to determine concentrations of (A) IL-15, (B) granzyme B, (C) CCL2, (D) CCL7, (E) CCL8, (F) CXCL1, (G) CXCL10, (H) CXCL11, and (I) CXCL12α in COVID-19 and influenza BAL fluid samples. (J) BAL fluid neutrophil counts. (K and L) ELISA was used to determine (K) SLPI and (L) elafin concentrations in the BAL fluids. All COVID-19 samples were categorized based on the absence of a coinfection (n = 6) or the acute phase (n = 11) or mid/late phase of a bacterial coinfection (n = 12) based on the timing of the BAL sampling relative to the coinfection time course. Influenza patient samples were also categorized in the acute phase (n = 8) and the mid/late phase (n = 5) of a bacterial coinfection. Data are shown as box-and-whisker plots (box: median with interquartile range, whiskers: full data distribution), with each dot representing an individual patient sample. The dashed lines indicate the lower detection limits. In the mid/late groups, unfilled symbols indicate samples taken during the late phase of the bacterial coinfection; the others were taken during the midphase of the bacterial coinfection. Triangles indicate samples with an additional fungal coinfection. Data were statistically analyzed by a linear mixed model with correction for multiple samples per patient using a random intercept model or a Mann-Whitney U test, where appropriate. P values are shown above brackets.