Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy-Reference-Cited by-同舟云学术

Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy

Published:2024-03-26 Issue:3 Volume:9 Page:
ISSN:2379-5042
Container-title:mSphere
language:en
Short-container-title:mSphere

Author:

St Clair Laura A.¹,Eldesouki Raghda E.²³,Sachithanandham Jaiprasath¹,Yin Anna¹,Fall Amary²,Morris C. Paul²⁴,Norton Julie M.²,Abdullah Omar²,Dhakal Santosh¹^ORCID,Barranta Caelan¹,Golding Hana⁵,Bersoff-Matcha Susan J.⁶,Pilgrim-Grayson Catherine⁷,Berhane Leah⁷,Cox Andrea L.¹⁸⁹,Burd Irina¹⁰,Pekosz Andrew¹⁸¹¹^ORCID,Mostafa Heba H.²^ORCID,Klein Eili Y.¹¹¹²^ORCID,Klein Sabra L.¹⁸^ORCID

Affiliation:

1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA

2. Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

3. Medical Genetics Unit, School of Medicine, Suez Canal University, Ismailia, Egypt

4. National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA

5. Division of Viral Products, Center of Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

6. Office of Women’s Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

7. Division of Urology, Obstetrics, and Gynecology, Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine and Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

8. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

9. Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

10. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA

11. Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

12. Center for Disease Dynamics, Economics, and Policy, United Nations Office for Disease Risk Reduction, Washington DC, USA

Abstract

ABSTRACT Pregnant patients are at greater risk of hospitalization with severe COVID-19 than non-pregnant people. This was a retrospective observational cohort study of remnant clinical specimens from patients who visited acute care hospitals within the Johns Hopkins Health System in the Baltimore, MD–Washington DC, area between October 2020 and May 2022. Participants included confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pregnant people and matched non-pregnant people (the matching criteria included age, race/ethnicity, area deprivation index, insurance status, and vaccination status to ensure matched demographics). 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. A total of 452 individuals (117 pregnant and 335 non-pregnant) were included in the study, with both vaccinated and unvaccinated individuals represented. Pregnant patients were at increased risk of hospitalization (odds ratio [OR] = 4.2; confidence interval [CI] = 2.0–8.6), intensive care unit admittance (OR = 4.5; CI = 1.2–14.2), and being placed on supplemental oxygen therapy (OR = 3.1; CI = 1.3–6.9). Individuals infected during their third trimester had higher mucosal anti-S IgG titers and lower viral RNA levels ( P < 0.05) than those infected during their first or second trimesters. Pregnant individuals experiencing breakthrough infections due to the Omicron variant had reduced anti-S IgG compared to non-pregnant patients ( P < 0.05). The 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 through booster vaccines may be important for the protection of this at-risk population. IMPORTANCE In this retrospective observational cohort study, we analyzed remnant clinical samples from non-pregnant and pregnant individuals with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who visited the Johns Hopkins Hospital System between October 2020 and May 2022. Disease severity, including intensive care unit admission, was greater among pregnant than non-pregnant patients. Vaccination reduced recovery of infectious virus and viral RNA levels in non-pregnant patients, but not in pregnant patients. In pregnant patients, increased nasopharyngeal viral RNA levels and recovery of infectious virus were associated with reduced mucosal IgG antibody responses, especially among women in their first trimester of pregnancy or experiencing breakthrough infections from Omicron variants. Taken together, this study provides insights into how pregnant patients are at greater risk of severe COVID-19. The novelty of this study is that it focuses on the relationship between the mucosal antibody response and its association with virus load and disease outcomes in pregnant people, whereas previous studies have focused on serological immunity. Vaccination status, gestational age, and SARS-CoV-2 omicron variant impact mucosal antibody responses and recovery of infectious virus from pregnant patients.

Funder

HHS | U.S. Food and Drug Administration

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Link

https://journals.asm.org/doi/pdf/10.1128/msphere.00812-23

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