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THE SYSTEMIC INFLAMMATORY LANDSCAPE OF COVID-19 IN PREGNANCY: EXTENSIVE SERUM PROTEOMIC PROFILING OF MOTHER-INFANT DYADS WITH IN UTERO SARS-COV-2
Foo, Suan-Sin et al. | Date Issued: 2021
Author
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 Farias Meira de
Soni, Priya R.
Gibson, L. Caroline
Brasil, Patricia
Comhair, Suzy A. A.
Arumugaswami, Vaithilingaraja
Erzurum, Serpil C.
Rao, Rashmi
Jung, Jae U.
Nielsen-Saines, Karin
Affilliation
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Medicine. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Maternal-Fetal Medicine. Department of Obstetrics and Gynecology. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Neonatology. Department of Pediatrics. Los Angeles, CA, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Maternal-Fetal Medicine. Department of Obstetrics and Gynecology. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Medicine. Los Angeles, CA, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Medicine. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Medicine. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Department of Pathology and Laboratory Medicine. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Department of Pathology and Laboratory Medicine. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Maternal-Fetal Medicine. Department of Obstetrics and Gynecology. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Neonatology. Department of Pediatrics. Los Angeles, CA, USA.
University of California. David Geffen School of Medicine. Division of Neonatology. Department of Pediatrics. Los Angeles, CA, USA.
Georgetown University. School of Medicine. Washington, DC, USA.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Cedars-Sinai Medical Center. Department of Pediatrics. Los Angeles, CA, USA.
Cedars-Sinai Medical Center. Department of Pediatrics. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Cleveland Clinic. Lerner Research Institute. Respiratory Institute. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Department of Molecular and Medical Pharmacology. Los Angeles, CA, USA.
Cleveland Clinic. Lerner Research Institute. Respiratory Institute. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Division of Maternal-Fetal Medicine. Department of Obstetrics and Gynecology. Los Angeles, CA, USA.
Infection Biology Program. Department of Cancer Biology. Cleveland, OH, USA / Cleveland Clinic. Lerner Research Institute. Global Center for Pathogen Research and Human Health. Cleveland, OH, USA.
University of California. David Geffen School of Medicine. Division of Infectious Diseases. Department of Pediatrics. Los Angeles, CA, 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
Exposed infants
IFN-λ signaling
Mother-infant pairs
Pregnancy
Prenatal SARS-CoV-2 infection
Serum proteomics
SARS-CoV-2
 
Publisher
Elsevier
Citation
FOO, Suan-Sin et al. The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2. Cell Reports Medicine, v. 2, n. 11, p. 1-25, Nov. 2021.
DOI
10.1016/j.xcrm.2021.100453
ISSN
2666-3791