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

ABSTRACTPregnant 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...

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Main Authors: Laura A. St Clair, Raghda E. Eldesouki, Jaiprasath Sachithanandham, Anna Yin, Amary Fall, C. Paul Morris, Julie M. Norton, 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
Format: Article
Language:English
Published: American Society for Microbiology 2024-03-01
Series:mSphere
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/msphere.00812-23
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author Laura A. St Clair
Raghda E. Eldesouki
Jaiprasath Sachithanandham
Anna Yin
Amary Fall
C. Paul Morris
Julie M. Norton
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
author_facet Laura A. St Clair
Raghda E. Eldesouki
Jaiprasath Sachithanandham
Anna Yin
Amary Fall
C. Paul Morris
Julie M. Norton
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
author_sort Laura A. St Clair
collection DOAJ
description ABSTRACTPregnant 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.IMPORTANCEIn 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.
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spelling doaj.art-780c1d55e5b944859f02e0ab498190432024-04-05T01:32:09ZengAmerican Society for MicrobiologymSphere2379-50422024-03-019310.1128/msphere.00812-23Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancyLaura A. St Clair0Raghda E. Eldesouki1Jaiprasath Sachithanandham2Anna Yin3Amary Fall4C. Paul Morris5Julie M. Norton6Omar Abdullah7Santosh Dhakal8Caelan Barranta9Hana Golding10Susan J. Bersoff-Matcha11Catherine Pilgrim-Grayson12Leah Berhane13Andrea L. Cox14Irina Burd15Andrew Pekosz16Heba H. Mostafa17Eili Y. Klein18Sabra L. Klein19W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USADivision of Viral Products, Center of Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USAOffice of Women’s Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USADivision 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, USADivision 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, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USADepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USAW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USAABSTRACTPregnant 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.IMPORTANCEIn 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.https://journals.asm.org/doi/10.1128/msphere.00812-23COVID-19gestationbreakthrough infectionOmicron variantDelta variant
spellingShingle Laura A. St Clair
Raghda E. Eldesouki
Jaiprasath Sachithanandham
Anna Yin
Amary Fall
C. Paul Morris
Julie M. Norton
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
Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
mSphere
COVID-19
gestation
breakthrough infection
Omicron variant
Delta variant
title Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
title_full Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
title_fullStr Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
title_full_unstemmed Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
title_short Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
title_sort reduced control of sars cov 2 infection associates with lower mucosal antibody responses in pregnancy
topic COVID-19
gestation
breakthrough infection
Omicron variant
Delta variant
url https://journals.asm.org/doi/10.1128/msphere.00812-23
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