Maternal and cord blood inflammatory responses to SARS-CoV-2 infection with and without vaccination

Vaccination is protective against severe COVID-19 disease, yet whether vaccination reduces COVID-19-associated inflammation in pregnancy is not known. The objective of this study is to characterize maternal and cord cytokine profiles of acute SARS-CoV-2 infection post-vaccination, compared to acute unvaccinated infection and uninfected controls. 66 pregnant individuals enrolled in the MGH COVID-19 biorepository (March 2020-April 2022) were included. Maternal sera were collected at acute SARS-CoV-2 infection (< 20 days from positive test) in 26 unvaccinated and 21 vaccinated cases. Cord sera were analyzed if delivery occurred during acute infection (12 unvaccinated, 11 vaccinated cases). Maternal and cord sera from 19 never-infected dyads at term were analyzed. Cytokines were quantified using the Human Inflammation 20-Plex ProcartaPlex assay. Differences between groups were assessed by Mann Whitney U test. Spearman correlations between cytokines were calculated and p-values adjusted for multiple comparisons. A greater proportion of unvaccinated infection cases were severe/critical compared to vaccinated cases (10/26 vs. 0/21, p=0.01). Specific maternal cytokines were elevated in vaccinated cases compared to uninfected controls (IL4, p=0.04; IL17A, p=0.03; IFNγ, p=0.04, Fig. 1A). TNFα and CD62P – a marker of endothelial activation – were elevated in vaccinated compared to unvaccinated cases (p=0.01, p=0.02, Fig. 1A). Neither unvaccinated nor vaccinated infection resulted in elevated cord cytokines compared to controls (Fig. 1B). In infection cases, maternal cytokine levels were highly correlated, with vaccinated infection centered on TNFα and unvaccinated on IFNγ (Fig. 2A and B). Vaccination was not associated with lower maternal cytokine levels during acute SARS-CoV-2 infection compared to unvaccinated infection in this pilot study. Differences in maternal serum cytokine profiles may reflect vaccine-mediated priming of the immune system that might protect against severe disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)