SARS-CoV-2 infection elucidates features of pregnancy-specific immunity

Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and...

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Bibliographic Details
Published inCell reports (Cambridge) Vol. 43; no. 11; p. 114933
Main Authors Oh, Dong Sun, Kim, Eunha, Normand, Rachelly, Lu, Guangqing, Shook, Lydia L., Lyall, Amanda, Jasset, Olyvia, Demidkin, Stepan, Gilbert, Emily, Kim, Joon, Akinwunmi, Babatunde, Tantivit, Jessica, Tirard, Alice, Arnold, Benjamin Y., Slowikowski, Kamil, Goldberg, Marcia B., Filbin, Michael R., Hacohen, Nir, Nguyen, Long H., Chan, Andrew T., Yu, Xu G., Li, Jonathan Z., Yonker, Lael, Fasano, Alessio, Perlis, Roy H., Pasternak, Ofer, Gray, Kathryn J., Choi, Gloria B., Drew, David A., Sen, Pritha, Villani, Alexandra-Chloé, Edlow, Andrea G., Huh, Jun R.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.11.2024
Elsevier
Subjects
Adult
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
COVID-19
COVID-19 - blood
COVID-19 - immunology
COVID-19 - virology
CP: Immunology
cytokines
Cytokines - blood
Cytokines - metabolism
Female
Humans
immune cells
immune responses
Leukocytes, Mononuclear - immunology
maternal immune activation
Pregnancy
Pregnancy Complications, Infectious - blood
Pregnancy Complications, Infectious - immunology
Pregnancy Complications, Infectious - virology
SARS-CoV-2
SARS-CoV-2 - immunology
single-cell RNA-seq
T cells
COVID-19
CP: Immunology
SARS-CoV-2
pregnancy
maternal immune activation
single-cell RNA-seq
immune cells
cytokines
T cells
immune responses
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Summary:Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8+ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection. [Display omitted] •COVID-19 is associated with altered T cell responses in pregnant patients•Identified altered cytokine and chemokine levels in pregnant patients with COVID-19•scRNA-seq analyses reveal decreased ISG responses in pregnant patients with COVID-19•Severe/critical illness and maternal obesity are associated with additional immune dysfunction Oh et al. perform a comprehensive immune survey of COVID-19 in pregnant and non-pregnant women, identifying pregnancy-specific alterations in immune responses. These include altered T cell responses, monocyte function, chemokines and cytokines, and gut microbial composition. This work provides insights into how pregnancy shapes antiviral immunity.
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AUTHOR CONTRIBUTIONS
A.G.E. and J.R.H. conceptualized the study. A.G.E. supervised all the clinical aspects of the study, metadata generation, and results interpretation. J.R.H. supervised immune analyses. A.-C.V. managed and supervised scRNA-seq data generation and analyses. D.S.O., E.K., G.L., G.B.C., A.G.E., and J.R.H. designed experiments. D.S.O., E.K., G.L., R.N., A.L., and O.P. analyzed data. MGH COVID Collection & Processing Team, P.S., J.T., A.T., and B.Y.A., collected, processed, and generated samples and/or data from the MGH acute COVID-19 non-pregnant cohort, which was overseen by X.G.Y. and J.Z.L. L.L.S., O.J., S.D., E.G., J.K., and B.A. enrolled, collected, processed, and generated samples and phenotypic data from the MGB COVID-19 Pregnancy Biorepository, which was supervised by A.G.E. and K.J.G., and to which L.Y. and A.F. also contributed personnel support and resources. M.B.G., M.R.F, and N.H. oversaw the MGH acute COVID cohort. P.S., J.T., A.T., and B.Y.A. performed the single-cell multiomics experiments for the COVID-19 pregnancy cohort. R.N. performed single-cell data analysis. R.N., P.S., and A.-C.V. performed single-cell data analysis interpretation. D.A.D. and L.H.N. performed metagenomic sequencing and analysis, supervised by A.T.C. D.S.O., E.K., G.L., R.N., P.S., A.-C.V., A.G.E., and J.R.H. wrote the manuscript. All authors read or provided comments on the manuscript.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.114933