The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2

Suan-Sin Foo; Mary Catherine Cambou; Thalia Mok; Viviana M Fajardo; Kyle L Jung; Trevon Fuller; Weiqiang Chen; Tara Kerin; Jenny Mei; Debika Bhattacharya; Younho Choi; Xin Wu; Tian Xia; Woo-Jin Shin; Jessica Cranston; Grace Aldrovandi; Nicole Tobin; Deisy Contreras; Francisco J Ibarrondo; Otto Yang; Shangxin Yang; Omai Garner; Ruth Cortado; Yvonne Bryson; Carla Janzen; Shubhamoy Ghosh; Sherin Devaskar; Brenda Asilnejad; Maria Elisabeth Moreira; Zilton Vasconcelos; Priya R Soni; L Caroline Gibson; Patricia Brasil; Suzy A A Comhair; Vaithilingaraja Arumugaswami; Serpil C Erzurum; Rashmi Rao; Jae U Jung; Karin Nielsen-Saines

doi:10.1016/j.xcrm.2021.100453

The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2

Cell Rep Med. 2021 Nov 16;2(11):100453. doi: 10.1016/j.xcrm.2021.100453. Epub 2021 Oct 27.

Authors

Suan-Sin Foo¹, Mary Catherine Cambou², Thalia Mok³, Viviana M Fajardo⁴, Kyle L Jung¹, Trevon Fuller⁵, Weiqiang Chen¹, Tara Kerin⁶, Jenny Mei³, Debika Bhattacharya², Younho Choi¹, Xin Wu¹, Tian Xia¹, Woo-Jin Shin¹, Jessica Cranston⁶, Grace Aldrovandi⁶, Nicole Tobin⁶, Deisy Contreras⁶, Francisco J Ibarrondo², Otto Yang², Shangxin Yang⁷, Omai Garner⁷, Ruth Cortado⁶, Yvonne Bryson⁶, Carla Janzen³, Shubhamoy Ghosh⁴, Sherin Devaskar⁴, Brenda Asilnejad⁸, Maria Elisabeth Moreira⁹, Zilton Vasconcelos⁹, Priya R Soni¹⁰, L Caroline Gibson¹⁰, Patricia Brasil⁵, Suzy A A Comhair¹¹, Vaithilingaraja Arumugaswami¹², Serpil C Erzurum¹¹, Rashmi Rao³, Jae U Jung¹, Karin Nielsen-Saines⁶

Affiliations

¹ Department of Cancer Biology, Infection Biology Program, and Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
² Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro 21040-360, Brazil.
⁶ Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁸ Georgetown University School of Medicine, Washington, DC 20007, USA.
⁹ Instituto Fernades Figueira, Fiocruz, Flamengo, Rio de Janeiro 20140-360, Brazil.
¹⁰ Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90049, USA.
¹¹ Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
¹² Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

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.

Keywords: COVID-19; COVID-19-exposed infants; IFN-λ signaling; mother-infant pairs; pregnancy; prenatal SARS-CoV-2 infection; serum proteomics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
COVID-19 / blood
COVID-19 / immunology*
COVID-19 / metabolism
Cytokines / blood*
Female
Humans
Infant, Newborn
Inflammation*
Mothers
Pregnancy
Proteomics*
Serum / metabolism
Young Adult

Substances

Cytokines

Abstract

Publication types

MeSH terms

Substances

Grants and funding