(257) Sex differences in cytokine profiles of the maternal-fetal dyad in acute SARS-CoV-2 infection

Thursday, February 9, 2023

10:30 AM – 12:00 PM

Objective: Prior work has demonstrated sexually dimorphic maternal and placental immune responses to COVID-19. The objective of this study is to assess the impact of fetal sex on maternal and cord cytokine profiles in acute SARS-CoV-2 infection.

Study Design: 57 individuals enrolled in the MGH COVID-19 biorepository (March 2020-April 2022) with a singleton pregnancy and known infant sex were included. Maternal sera were obtained during acute SARS-CoV-2 infection ( < 20 days from positive test, N=38: 17 female, 21 male cases); groups were balanced by disease severity. Cord sera were analyzed if delivery occurred during acute infection (N=23). Sera from 19 dyads never infected with SARS-CoV-2 were collected at delivery and analyzed (N=10 female, 9 male controls). Cytokines were quantified using the Human Inflammation 20-Plex ProcartaPlex assay. The impact of fetal sex and SARS-CoV-2 positivity on cytokine concentration was assessed by 2-way ANOVA, followed by Tukey’s post-hoc analysis.

Results: Infection was associated with higher IL4 (SARS-CoV-2 positivity: p=0.02) and a trend toward higher IFNα (SARS-CoV-2 positivity: p=0.09) in maternal sera– Fig. 1. There was no significant effect of fetal sex on maternal cytokines assessed. In cord sera, a significant interaction effect of fetal sex and maternal SARS-CoV-2 was observed in IL1β, IL13, and TNFα (interaction p=0.005, p=0.003, p=0.02, respectively) – Fig. 2. Cytokine levels were lower in cases compared to controls in males but not females, and slightly though not significantly elevated in females, reflecting a sexually dimorphic response to maternal SARS-CoV-2 in the cord.

Conclusion: Fetal sex impacts specific cord but not maternal cytokines in acute SARS-CoV-2 infection in this pilot study. The higher cytokine baseline apparent in male cord sera from uninfected pregnancies may have implications for male offspring disease liability. Further investigation into the mechanism and source of these sex differences, and their potential clinical implications, is warranted.

Primary & Presenting Author(s)

Lydia Shook, MD
Instructor
Massachusetts General Hospital
Waban, Massachusetts, United States

Coauthor(s)

Molly R. Siegel, MD
MFM Fellow
Department of Obstetrics and Gynecology, Massachusetts General Hospital
Boston, Massachusetts, United States
SB
Sara Brigida, BS
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States
KA
Kalpana D. Acharya, PhD
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States
SD
Stepan Demidkin, BA
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States
CM
Cordelia Muir, BA
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States
AM
Arantxa Medina Baez, BA
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States
RP
Roy H. Perlis, MD, MSc
Massachusetts General Hospital, Center for Quantitative Health
Boston, Massachusetts, United States
Andrea G. Edlow, MD, MSc (she/her/hers)
MFM Staff, Principal Investigator
Massachusetts General Hospital, Department of Obstetrics and Gynecology
Boston, Massachusetts, United States