Fig. 3. Limited IgG responses against SARS-CoV-2 Spike at DSO11 are associated with mortality.

(A) ELISA-based relative quantification of SARS-CoV-2 RBD-specific antibodies’ isotypes IgM (left), IgA (middle), or IgG (right) in relative light units (RLU) normalized to an internal control (CR3022). (B to D) Comparison of functional properties of the plasma of all three groups, namely, (B) plasma capacity to recognize the SARS-CoV-2 full Spike (Spike Ig) using a flow cytometry–based assay [median fluorescence intensity (MFI)], (C) plasma neutralization activity [unit: half of maximal inhibitory plasma dilution (ID₅₀)], and (D) plasma ADCC activity (unit: % of ADCC-mediated killing). (E and F) Correlation matrices with colors representing the Spearman R value (blue: negative association −1; red: positive association 1) and P values indicated as * in the circles, (E) between all serology measurements or (F) of serology measurements versus plasma vRNA and plasma analytes. (G to J) Comparison of serology measurements in patients who survived (white column) or deceased (gray column) by DSO60 for (G) RBD-specific IgM (left), IgA (middle), or IgG (right) or (H) full Spike binding, (I) neutralization, or (J) ADCC. (K) Hazard ratio with 95% CI calculated using Cox regression for an increase of 1 U of log₁₀-transformed (square) or 10 U (diamond) of serology measurements. (L to N) Modelization of the predicted survival curves of patients with high (orange; upper IQR) or low (purple; lower IQR) (L) RBD-specific IgG, (M) Spike Ig, or (N) ADCC activity in all patients with COVID-19. (A to D) Kruskal-Wallis with Dunn’s multiple comparisons test. (E and F) Spearman R correlation. (F) Cytokines with titles annotated by ∅ are poorly detected. (G to J) Mann-Whitney test. For (G) to (J), color-coded dots represent severity of the patient at DSO11 (red: critical; blue: noncritical), and the dotted line represents the limit of detection. (E, F, and L) *P < 0.05; **P < 0.01; ***P < 0.001. n = 61 COVID-19 subjects (13 mortalities) or 29 critical COVID-19 cases (11 mortalities) and 43 UC. IQR: calculated within the COVID-19 discovery cohort.