ABSTRACT
Background: Pregnancy being immune compromised state, COVID-19 disease poses a high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses and we aimed to analyze the plasma secretome, metabolome, and immune cells in COVID-19-positive pregnant mothers and cord blood. Methods: COVID-19 RT-PCR positive pregnant females (n=112) asymptomatic (n=82), or with mild (n=21) or moderate (n=9) disease and control healthy pregnant (n=10) females were included. Mothers blood and cord blood (n=80) was analyzed for untargeted metabolome profiling and plasma cytokines by high-resolution mass spectrometry (MS) and multiplex cytokine bead array. Immune scan in mothers was done using flow cytometry. Results: In asymptomatic SARS-CoV-2 infection, the amino acid metabolic pathways such as glycine, serine, L-lactate, and threonine metabolism was upregulated, riboflavin and tyrosine metabolism, downregulated. In mild to moderate disease, the pyruvate and NAD+ metabolism (energy metabolic pathways) were mostly altered. In addition to raised TNF-alpha, IFN-alpha, IFN-gamma, IL-6 cytokine storm, IL-9 was increased in both mothers and neonates. Pyruvate and NAD+ metabolic pathways along with IL-9 and IFN-gamma had an impact on non-classical monocytes, increased CD4 T cells and B cells but depleted CD8+ T cells. Cord blood mimicked the mothers metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in asymptomatic and NAD+ and riboflavin metabolism in mild and moderate disease subjects. Conclusions: Our results demonstrate a graduated immune-metabolomic interplay in mother and fetus in pregnant females with different degrees of severity of COVID-19 disease. IL-9 and IFN- gamma regulated pyruvate, lactate TCA metabolism, and riboflavin metabolism with context to disease severity are hallmarks of this materno-fetal metabolome.