Figure 6. Circulating cytokines and lipid mediators (LMs) during the acute and post-acute phases of SARS-CoV-2 infection.

(A) Principal component analysis of serum cytokines in the acute phase of the disease (1–7 dpi) and the post-acute phase of disease (10–21 dpi). The first principal component is on the x-axis and the second is on the y-axis. The f-statistic and P-value for clustering across all significant principal components (up to 99% explained variance) is shown from a PERMANOVA test. Green points represent younger and grey represent older animals. (B) PC1 loading scores for serum cytokines in the post-acute phase of the disease. The vertical dashed line represents the cutoff for the significant loading values highlighted in the yellow box. (C) Serum cytokine levels over the course of infection in the older and younger animals for the cytokines that pass the threshold in panel (B). P-values in the acute phase of the disease (0–7 dpi, outside blue box) and the post-acute phase of the disease (10–21 dpi, inside blue box) represent a comparison of the area under the curve between the older and younger animals using an unpaired t test. Lines represent the mean and error bars represent the SEM at each time point. (D) Circulating LM profiles for the older (left) and younger (right) animals over the course of the infection (0, 3, 7, and 21 dpi). Each column represents a single animal, and the rows indicate specific LM. LMs are grouped by the synthesizing lipoxygenase (LO) enzyme noted on the right of the heat map. LM species produced by multiple LO enzymes are listed with each family. Values represent the log₂ -fold change compared to day 0 with blue meaning a decrease and red meaning an increase. (E) PC1 loading values for the indicated LMs at 3 and 21 dpi. Boxes represent groupings of different LM classes denoted to the right of each group. (F) PC1 values for individual animals at 3 and 21 dpi with old on the left of the line and young to the right of the line.