(713) Fetal sex influences the maternal plasma proteome in SARS-CoV-2 including anti-viral response

Friday, January 31, 2025

10:30 AM – 12:30 PM

Submitting Author and Presenting Author(s)

BP

Bogdan Panaitescu, MD, PhD

MFM Fellow
Wayne State University School of Medicine
Detroit, Michigan, United States

Coauthor(s)

Roberto Romero, MD

Chief
Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver NICHD, NIH, DHHS, Bethesda, Maryland, USA
Bethesda, Maryland, United States
Nardhy Gomez-Lopez, PhD (she/her/hers)

Professor
Center for Reproductive Health Sciences, Washington University School of Medicine
St. Louis, Missouri, United States
ME

Maria Fernanda Escobar, MD

Universidad Icesi, School of Medicine
Cali, Valle del Cauca, Colombia
GB

Gaurav Bhatti, PhD

Center for Molecular Medicine and Genetics, Wayne State University School of Medicine
Detroit, Michigan, United States
VT

Victor Tarca

Huron High School
Ann Arbor, Michigan, United States
TP

Tanay Panja

Huron High School
Ann Arbor, Michigan, United States
AM

Arun Mezzayhagan, PhD

Wayne State University School of Medicine
Detroit, Michigan, United States
AA

Awoniyi Awonuga, MD

Wayne State University School of Medicine
Detroit, Michigan, United States
TC

Tinnakorn Chaiworapongsa, MD

Professor
Wayne State University School of Medicine
Detroit, Michigan, United States
DB

David R. Bryant, MD

Wayne State University School of Medicine
Detroit, Michigan, United States
AT

Adi L. Tarca, PhD

Professor
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine
Detroit, Michigan, United States

Objective: Fetal sex influences physiological and pathological processes during pregnancy. This study was designed to determine the impact of fetal sex on the maternal response to SARS-CoV-2 infection using large-scale proteomics.

Study Design: This was a prospective observational study of 101 pregnant patients, including 72 with confirmed SARS-CoV-2 infection and 29 controls without infection. Severity was assigned according to the NIH classification for COVID-19. Large-scale plasma proteomics was undertaken with the SomaScan platform, which analyzes 7,288 proteins. Fetal sex-specific changes in the maternal proteome was assessed using linear models and moderated t-tests while accounting for COVID-19 severity and relevant clinical co-variates.

Results: 1) In normal pregnancy, fetal sex did not alter the maternal plasma proteome; 2) SARS-CoV-2 infection during pregnancy exhibited a fetal sex-dependent modulation of the plasma proteome; 3) pregnancies with a male fetus had a lower magnitude of plasma proteomic responses to SARS-CoV-2 infection compared to those with a female fetus (see figure; slope=0.44, r=0.61, p< 0.001); 4) the dampened maternal plasma proteomic response to infection in pregnancies with a male fetus was also noted according to disease severity; and 5) in severe COVID-19, proteins showing fetal sex-specific magnitude of change (interaction p< 0.05) were enriched for antiviral response pathways, endocytosis, and VEGF signaling, among others (adjusted p< 0.1).

Conclusion: 1) Fetal sex dimorphism in the maternal proteome is not present in normal pregnancy, but in patients with COVID-19; 2) pregnancies with male fetuses had a dampened proteomic response; and 3) these findings suggest that fetal sex is an important factor modulating the maternal response during SARS-CoV-2 infection and may determine disease progression and outcome.