- Foo, Suan-Sin;
- Cambou, Mary Catherine;
- Mok, Thalia;
- Fajardo, Viviana M;
- Jung, Kyle L;
- Fuller, Trevon;
- Chen, Weiqiang;
- Kerin, Tara;
- Mei, Jenny;
- Bhattacharya, Debika;
- Choi, Younho;
- Wu, Xin;
- Xia, Tian;
- Shin, Woo-Jin;
- Cranston, Jessica;
- Aldrovandi, Grace;
- Tobin, Nicole;
- Contreras, Deisy;
- Ibarrondo, Francisco J;
- Yang, Otto;
- Yang, Shangxin;
- Garner, Omai;
- Cortado, Ruth;
- Bryson, Yvonne;
- Janzen, Carla;
- Ghosh, Shubhamoy;
- Devaskar, Sherin;
- Asilnejad, Brenda;
- Moreira, Maria Elisabeth;
- Vasconcelos, Zilton;
- Soni, Priya R;
- Gibson, L Caroline;
- Brasil, Patricia;
- Comhair, Suzy AA;
- Arumugaswami, Vaithilingaraja;
- Erzurum, Serpil C;
- Rao, Rashmi;
- Jung, Jae U;
- Nielsen-Saines, Karin
While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1β/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.