Figure 9.

Effects of human COVID-19 post-vaccination sera on tissue-specific cytokines and D-dimer deposition of K18-hACE2 mice challenged with SARS-CoV-2 and variants

K18-hACE2 mice of both sexes (1:1 ratio, n = 6 mice/group) were injected intraperitoneally with 200 μL/mouse of PBS (mock-transferred) or pooled human post-vaccination (post-vac) sera collected at 1-month after the 2^nd dose of COVID-19 mRNA vaccines (post-vac sera transferred). Recipient mice were then challenged intranasally with 10³ TCID₅₀/mouse of New York-PV09158/2020 (NY (614G)), or 10² TCID₅₀/mouse of Kappa and Delta variants. D-dimer and cytokines in brain, heart, lung, and liver homogenates harvested on 5 days post-infection were measured (Individual D-dimer and cytokine levels shown in Figures S7 and S8). Fold changes in tissue-specific cytokine and D-dimer levels of post-vac sera transferred mice vs mock-transferred mice are shown, including (A) CXCL10/IP-10, (B) MCP-1, (C)CMIP-1α, (D) MIP-2, (E) IL-1β, (F) IL-6, (G) IL-10, (H) TNF-α, (I) IFN-β and (J) D-dimer. Tissue-specific viral loads, cytokines, and D-dimer of post-vac sera transferred mice and mock-transferred mice were also subjected to multivariate principal component analysis (PCA).

(K, M, and N) The most significant two principal components (PC1 and PC2) are shown for NY (614G) (K), Kappa (M) or Delta challenge (N), respectively. Only in NY (614G) challenged mice, those receiving post-vac sera were fully separated from mock-transferred (K).

(L) The variable importance in projection (VIP) scores for NY (614G) challenge is shown after the logistic regression accounting for different tissues. ∗p < 0.05, ∗∗p < 0.01 by the Wald test.