Fig. 1: Hospitalized patients display four distinct endotypes of early plasma immunovirological profiles following SARS-CoV-2 infection.

A Study design. Serial blood samples were collected among hospitalized NSW PCR-confirmed COVID-19+ patients. Samples were assessed for plasma viral RNA, seven cytokines, three tissue damage markers, and three SARS-CoV-2 RBD-specific antibody isotypes. On samples collected 11 (+/−4) days after symptom onset (DSO11), all 14 parameters were combined for visualization by PHATE and used to calculate patient clusters by k-means. Patient cluster was then used to color-code PHATE embedding. B DSO11 samples identified four patient clusters across 242 hospitalized COVID-19+ patients. C–F At DSO11, plasma concentration across four patient clusters of (C) viral RNA; (D) Cytokine Score obtained from the linear combination of all seven cytokines; (E) score of tissue damage obtained from the linear combination of all three markers of tissue damage, and (F) SARS-CoV-2 RBD-specific IgG. G, H Percentage of the whole cohort or per patient cluster (G) with critical (hashed), severe (saturated), or moderate (faint) disease; (H) with fatal outcome (hashed). I Summary table of four patient clusters in the discovery cohort. J Validation cohort of 76 hospitalized COVID-19+ patients. SARS-CoV-2-specific IgG, IgM and IgA, vRNA and cytokines and tissue damage markers were measured at DSO11. PHATE embedding and k-means clustering were performed as for the discovery cohort. K–O Comparison, between validation cluster (V)1 and V2, of plasma levels of (K) SARS-CoV-2 vRNA; (L) IL-6; (M) RAGE or (N) N-specific IgG. O Outcome at DSO60 (hashed being fatal outcome). N discovery cohort: 1 = 38; 2 = 49; 3 = 73; 4 = 82 (242 in total). N validation cohort: V1 = 37; V2 = 39 (76 in total). C–F Kruskal-Wallis with Dunn’s multiple comparison tests. Adjusted p values are shown. G, H Two-sided Fisher’s exact test compares the proportion of hashed groups in one cluster versus all others. For (G), statistical comparison is between critical and non-critical. K–O Two-sided Mann-Whitney tests. Medians are shown in bar charts. Source data are provided as Source_Data_File.xlsx.