Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

Biasi, Sara De; Tartaro, Domenico Lo; Gibellini, Lara; Paolini, Annamaria; Quong, Andrew A.; Petes, Carlene; Awong, Génève; Douglas, Samuel; Lin, Derek; Nieto, Jordan; Borella, Rebecca; Fidanza, Lucia; Mattioli, Marco; Leone, Chiara; Meschiari, Marianna; Franceschini, Erica; Cicchetti, Luca; Trenti, Tommaso; Sarti, Mario; Girardis, Massimo; Guaraldi, Giovanni; Mussini, Cristina; Facchinetti, Fabio; Cossarizza, Andrea

doi:10.21203/rs.3.rs-263619/v1

Cited by 7 publications

(18 citation statements)

References 19 publications

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“…Myeloid DC frequency and their surface expression of HLA-DR and CD86 remained unchanged with disease. These findings are in line with a recently profiled blood immune cells and plasma in pregnant women with asymptomatic disease, where limited immune changes in PBMC composition and cytokine milieu were observed (13). We posit that these differences are driven by Th2 bias observed with pregnancy that may limit inflammation and reinforce immune tolerance (11).…”

Section: Discussionsupporting

confidence: 89%

“…This immune adaptation with pregnancy does not preclude pregnant women from developing an effective adaptive immune response to the virus since T cells from pregnant mothers with asymptomatic disease have been shown to be functionally competent with respect to ex vivo cytokine production and proliferation (13). Our data indicate reduction in naïve CD4 T cells, and expansion of CD8 memory T cells (TEMRA), in addition to enrichment of cytotoxic CD4 and PD1+ antiviral CD8 T cells with infection.…”

Section: Discussionmentioning

confidence: 73%

“…While T cells in pregnant mothers with asymptomatic COVID-19 have been shown to be functional (13), activated CD4 and CD8 T cells were detected in both blood and decidua.…”

Section: Discussionmentioning

confidence: 96%

“…These differences are primarily driven by peripheral immune adaptations during pregnancy (11,12) that balance fetal tolerance and growth with host defense. Recent analysis of the peripheral immune system of mothers with asymptomatic disease revealed an increase in low-density neutrophils (LDN) but no gross changes in leukocyte frequencies, activation, and function (13). Furthermore, the cytokine storm that is characteristic of severe COVID-19 in the general population is hardly reported in cases of severe COVID-19 amongst pregnant patients (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection

Sureshchandra

Zulu

Doratt

et al. 2021

Preprint

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Pregnant women are an at-risk group for severe COVID-19, though the majority experience mild/asymptomatic disease. Although severe COVID-19 has been shown to be associated with immune activation at the maternal-fetal interface even in the absence of active viral replication, the immune response to asymptomatic/mild COVID-19 remains unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic/mild disease and 15 pregnant SARS-naive women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling but upregulation of inflammatory cytokines and chemokines in blood monocyte derived decidual macrophages. On the other hand, infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of Tregs. Interestingly, frequencies of cytotoxic CD4 and CD8 T cells increased only in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. The resulting aberrant immune activation in the placenta, even with asymptomatic disease may alter the exquisitely sensitive developing fetal immune system, leading to long-term adverse outcomes for offspring.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 73%

“…While T cells in pregnant mothers with asymptomatic COVID-19 have been shown to be functional (13), activated CD4 and CD8 T cells were detected in both blood and decidua.…”

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection

Sureshchandra

Zulu

Doratt

et al. 2021

Preprint

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“…Finally, we identi ed low density neutrophils [CD66b + CXCR1 + CCR6 + (LDN)] as those cells present among mononuclear cells after isolation by using Ficoll Hypaque, as previously described 25 (Figure 2b).…”

Section: Different Distribution and Proliferative Capacity Of T And B...mentioning

confidence: 99%

Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia

Tartaro

Neroni

Paolini

et al. 2022

Preprint

Self Cite

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Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4+ T cells, specific antibodies are reported along with features of lung macrophages. Elderly subjects have higher levels of pro-inflammatory cytokines, more circulating plasmablasts, reduced plasmatic level of anti-S and anti-RBD IgG3 antibodies, lower proportions of central memory CD4+ T cells, more immature monocytes and CD56+ pro-inflammatory monocytes, lower percentages of circulating follicular helper T cells (cTfh), antigen-specific cTfh cells with a less activated transcriptomic profile, lung resident activated macrophages that promote collagen deposition and fibrosis. Our study underlines the importance of inflammation in the response to SARS-CoV-2 and suggests that inflammaging, coupled with the inability to mount a proper anti-viral response, could exacerbate disease severity and the worst clinical outcome in old patients.

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Is pregnancy a risk factor for in‐hospital mortality in reproductive‐aged women with SARS‐CoV‐2 infection? A nationwide retrospective observational cohort study

Leung

Paiva

2021

Intl J Gynecology & Obste

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Objective To examine the effect of pregnancy on coronavirus disease 2019 (COVID‐19) ‐related in‐hospital mortality in women of reproductive age (between 15 and 45 years), with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection confirmed with polymerase chain reaction tests, adjusted for factors such as co‐infection and intervention that were not considered in existing literature. Methods Data gathered from a nationwide database in Brazil were analyzed using multivariate logistic regression and multivariate Cox regression. Adjusted odds ratios and hazard ratios of independent factors associated with in‐hospital death were calculated. Results A total of 97 712 women were included in the study. After the adjustment for sociodemographic factors, epidemiologic characteristics, pre‐existing medical conditions, and intervention, pregnant women were found to be associated with lower risk for in‐hospital mortality as well as longer survival time compared with non‐pregnant women. When covariates of intervention were omitted from the analysis, pregnancy did not appear to be a significant factor associated with mortality. Conclusion With the adjustment for intervention that was shown to be an independent factor associated with mortality, pregnancy appeared to have a favorable effect on SARS‐CoV‐2 infection. Given the immunosuppressed state of pregnancy, this finding is in line with the hypothetical protective role of a weaker immune response that inhibits the production of proinflammatory cytokine.

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Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection

Cited by 7 publications

References 19 publications

Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection

Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection

Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia

Is pregnancy a risk factor for in‐hospital mortality in reproductive‐aged women with SARS‐CoV‐2 infection? A nationwide retrospective observational cohort study

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