Reduced control of SARS-CoV-2 infection is associated with lower mucosal antibody responses in pregnant women

Laura A St Clair; Raghda E Eldesouki; Jaiprasath Sachithanandham; Anna Yin; Amary Fall; C Paul Morris; Julie M Norton; Michael Forman; Omar Abdullah; Santosh Dhakal; Caelan Barranta; Hana Golding; Susan J Bersoff-Matcha; Catherine Pilgrim-Grayson; Leah Berhane; Andrea L Cox; Irina Burd; Andrew Pekosz; Heba H Mostafa; Eili Y Klein; Sabra L Klein

doi:10.1101/2023.03.19.23287456

Reduced control of SARS-CoV-2 infection is associated with lower mucosal antibody responses in pregnant women

medRxiv [Preprint]. 2023 Mar 20:2023.03.19.23287456. doi: 10.1101/2023.03.19.23287456.

Authors

Laura A St Clair¹, Raghda E Eldesouki^{2

3}, Jaiprasath Sachithanandham¹, Anna Yin¹, Amary Fall², C Paul Morris^{2

4}, Julie M Norton², Michael Forman², Omar Abdullah², Santosh Dhakal¹, Caelan Barranta¹, Hana Golding⁵, Susan J Bersoff-Matcha⁶, Catherine Pilgrim-Grayson⁷, Leah Berhane⁷, Andrea L Cox^{1

8

9}, Irina Burd¹⁰, Andrew Pekosz^{1

8

11}, Heba H Mostafa², Eili Y Klein^{11

12}, Sabra L Klein^{1

8}

Affiliations

¹ W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
² Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Medical Genetics Unit, Histology Department, School of Medicine, Suez Canal University, Egypt.
⁴ National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
⁵ Division of Viral Products, Center of Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
⁶ Office of Women's Health, U.S. Food and Drug Administration, Silver Spring, MD, USA.
⁷ Division of Urology, Obstetrics, and Gynecology; Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine; Office of New Drugs; Center for Drug Evaluation and Research; U.S. Food and Drug Administration, Silver Spring, MD, USA.
⁸ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
¹¹ Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹² Center for Disease Dynamics, Economics, and Policy, Washington DC, USA.

Abstract

Importance: Pregnant women are at increased risk of severe COVID-19, but the contribution of viral RNA load, the presence of infectious virus, and mucosal antibody responses remain understudied.

Objective: To evaluate the association of COVID-19 outcomes following confirmed infection with vaccination status, mucosal antibody responses, infectious virus recovery and viral RNA levels in pregnant compared with non-pregnant women.

Design: A retrospective observational cohort study of remnant clinical specimens from SARS-CoV-2 infected patients between October 2020-May 2022.

Setting: Five acute care hospitals within the Johns Hopkins Health System (JHHS) in the Baltimore, MD-Washington, DC area.

Participants: Participants included confirmed SARS-CoV-2 infected pregnant women and matched non-pregnant women (matching criteria included age, race/ethnicity, and vaccination status).

Exposure: SARS-CoV-2 infection, with documentation of SARS-CoV-2 mRNA vaccination.

Main outcomes: The primary dependent measures were clinical COVID-19 outcomes, infectious virus recovery, viral RNA levels, and mucosal anti-spike (S) IgG titers from upper respiratory tract samples. Clinical outcomes were compared using odds ratios (OR), and measures of virus and antibody were compared using either Fisher's exact test, two-way ANOVA, or regression analyses. Results were stratified according to pregnancy, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant.

Resultss: A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant women were at increased risk of hospitalization (OR = 4.2; CI = 2.0-8.6), ICU admittance, (OR = 4.5; CI = 1.2-14.2), and of being placed on supplemental oxygen therapy (OR = 3.1; CI =13-6.9). An age-associated decrease in anti-S IgG titer and corresponding increase in viral RNA levels (P< 0.001) was observed in vaccinated pregnant, but not non-pregnant, women. Individuals in their 3^rd trimester had higher anti-S IgG titers and lower viral RNA levels (P< 0.05) than those in their 1^st or 2^nd trimesters. Pregnant individuals experiencing breakthrough infections due to the omicron variant had reduced anti-S IgG compared to non-pregnant women (P< 0.05).

Conclusions and relevance: In this cohort study, vaccination status, maternal age, trimester of pregnancy, and infecting SARS-CoV-2 variant were each identified as drivers of differences in mucosal anti-S IgG responses in pregnant compared with non-pregnant women. Observed increased severity of COVID-19 and reduced mucosal antibody responses particularly among pregnant participants infected with the Omicron variant suggest that maintaining high levels of SARS-CoV-2 immunity may be important for protection of this at-risk population.

Keywords: COVID-19; Delta variant; Omicron variant; breakthrough infection; gestation.

Publication types

Preprint

Abstract

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