Cell Reports Medicine (Nov 2021)
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
Affiliations
- Suan-Sin Foo
- 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
- Mary Catherine Cambou
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Thalia Mok
- 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
- Viviana M. Fajardo
- Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Kyle L. Jung
- 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
- Trevon Fuller
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro 21040-360, Brazil
- Weiqiang Chen
- 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
- Tara Kerin
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Jenny Mei
- 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
- Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Younho Choi
- 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
- Xin Wu
- 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
- Tian Xia
- 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
- Woo-Jin Shin
- 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
- Jessica Cranston
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Grace Aldrovandi
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Nicole Tobin
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Deisy Contreras
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Francisco J. Ibarrondo
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Otto Yang
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Shangxin Yang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Omai Garner
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Ruth Cortado
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Yvonne Bryson
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Carla Janzen
- 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
- Shubhamoy Ghosh
- Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Sherin Devaskar
- Department of Pediatrics, Division of Neonatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Brenda Asilnejad
- Georgetown University School of Medicine, Washington, DC 20007, USA
- Maria Elisabeth Moreira
- Instituto Fernades Figueira, Fiocruz, Flamengo, Rio de Janeiro 20140-360, Brazil
- Zilton Vasconcelos
- Instituto Fernades Figueira, Fiocruz, Flamengo, Rio de Janeiro 20140-360, Brazil
- Priya R. Soni
- Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90049, USA
- L. Caroline Gibson
- Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90049, USA
- Patricia Brasil
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro 21040-360, Brazil
- Suzy A.A. Comhair
- Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Vaithilingaraja Arumugaswami
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
- Serpil C. Erzurum
- Respiratory Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
- Rashmi Rao
- 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
- Jae U. Jung
- 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; Corresponding author
- Karin Nielsen-Saines
- Department of Pediatrics, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 11
p. 100453
Abstract
Summary: 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.
