Reduced control of SARS-CoV-2 infection associates with lower mucosal antibody responses in pregnancy
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
Affiliations
Laura A. St Clair
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Raghda E. Eldesouki
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Jaiprasath Sachithanandham
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Anna Yin
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Amary Fall
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
C. Paul Morris
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Julie M. Norton
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Omar Abdullah
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Santosh Dhakal
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Caelan Barranta
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Hana Golding
Division of Viral Products, Center of Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Susan J. Bersoff-Matcha
Office of Women’s Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Catherine Pilgrim-Grayson
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
Leah Berhane
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
Andrea L. Cox
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Irina Burd
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA
Andrew Pekosz
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
Heba H. Mostafa
Department of Pathology, Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Eili Y. Klein
Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Sabra L. Klein
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
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.
