The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2

Foo, Suan-Sin; Cambou, Mary Catherine; Mok, Thalia; Fajardo, Viviana M.; Jung, Kyle L.; Fuller, Trevon; Chen, Weiqiang; Kerin, Tara; Mei, Jenny Y.; Bhattacharya, Debika; Choi, Younho; Wu, Xin; Xia, Tian; Shin, Woo Jin; Cranston, Jessica; Aldrovandi, Grace M.; Tobin, Nicole H.; Contreras, Deisy; Ibarrondo, F. Javier; Yang, Otto O.; Yang, Shangxin; Garner, Omai B.; Cortado, Ruth; Bryson, Yvonne J.; Janzen, Carla; Ghosh, Shubhamoy; Devaskar, Sherin U.; Asilnejad, Brenda; Moreira, Maria Elisabeth Lopes; Vasconcelos, Zilton; Soni, Priya; Gibson, Leena Caroline; Brasil, Patrícia; Comhair, Suzy; Arumugaswami, Vaithilingaraja; Erzurum, Serpil C.; Rao, Rashmi; Jung, Jae U.; Nielsen‐Saines, Karin

doi:10.1016/j.xcrm.2021.100453

Cited by 29 publications

(15 citation statements)

References 79 publications

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“…A recent report expounded upregulation of MK protein expression in plasma of COVID-19 patients ( 125 ). Also, another investigation described MK protein upregulation in sera of pregnant women with COVID-19, which was associated with pregnancy complications ( 126 ). In a similar study, MK serum levels in pregnant women with COVID-19 displayed a significant increase in contrast to healthy pregnant women ( 127 ).…”

Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

Midkine—A novel player in cardiovascular diseases

Majaj

Weckbach

2022

Front. Cardiovasc. Med.

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Midkine (MK) is a 13-kDa heparin-binding cytokine and growth factor with anti-apoptotic, pro-angiogenic, pro-inflammatory and anti-infective functions, that enable it to partake in a series of physiological and pathophysiological processes. In the past, research revolving around MK has concentrated on its roles in reproduction and development, tissue protection and repair as well as inflammatory and malignant processes. In the recent few years, MK's implication in a wide scope of cardiovascular diseases has been rigorously investigated. Nonetheless, there is still no broadly accepted consensus on whether MK exerts generally detrimental or favorable effects in cardiovascular diseases. The truth probably resides somewhere in-between and depends on the underlying physiological or pathophysiological condition. It is therefore crucial to thoroughly examine and appraise MK's participation in cardiovascular diseases. In this review, we introduce the MK gene and protein, its multiple receptors and signaling pathways along with its expression in the vascular system and its most substantial functions in cardiovascular biology. Further, we recapitulate the current evidence of MK's expression in cardiovascular diseases, addressing the various sources and modes of MK expression. Moreover, we summarize the most significant implications of MK in cardiovascular diseases with particular emphasis on MK's advantageous and injurious functions, highlighting its ample diagnostic and therapeutic potential. Also, we focus on conflicting roles of MK in a number of cardiovascular diseases and try to provide some clarity and guidance to MK's multifaceted roles. In summary, we aim to pave the way for MK-based diagnostics and therapies that could present promising tools in the diagnosis and treatment of cardiovascular diseases.

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Section: Discussion: Midkine In Cardiovascular Diseasesmentioning

confidence: 99%

Midkine—A novel player in cardiovascular diseases

Majaj

Weckbach

2022

Front. Cardiovasc. Med.

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“…Dysregulation of the Th1/Th2 and Th17/Treg balance and an increase in pro-inflammatory responses during viral respiratory infection is associated with worse disease outcomes and complications in pregnant people. 126 A mouse study found that pregnant mice infected with IAV 2009 pH1N1 had increased mortality and displayed signs of reduced epithelial regeneration and impaired lung repair, as well as elevated levels of Tregs in the lungs despite no significant increase in viral load. There was an increased infiltration of pulmonary neutrophils and macrophages strongly correlated with elevated mortality, as well as increased nitrites and several proinflammatory cytokines involved in cell recruitment to the lungs.…”

Section: Tregsandviralrespiratoryinfectionsmentioning

confidence: 99%

“…During pregnancy, there is a general attenuation of the maternal immune system skewing toward anti‐inflammatory responses. Dysregulation of the Th1/Th2 and Th17/Treg balance and an increase in pro‐inflammatory responses during viral respiratory infection is associated with worse disease outcomes and complications in pregnant people 126 . A mouse study found that pregnant mice infected with IAV 2009 pH1N1 had increased mortality and displayed signs of reduced epithelial regeneration and impaired lung repair, as well as elevated levels of Tregs in the lungs despite no significant increase in viral load.…”

Section: Regulatory T Cellsmentioning

confidence: 99%

Role of hormones in the pregnancy and sex‐specific outcomes to infections with respiratory viruses*

Cervantes

Talavera

Every

et al. 2022

Immunological Reviews

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Pregnant women infected with pathogenic respiratory viruses, such as influenza A viruses (IAV) and coronaviruses, are at higher risk for mortality, hospitalization, preterm birth, and stillbirth. Several factors are likely to contribute to the susceptibility of pregnant individuals to severe lung disease including changes in pulmonary physiology, immune defenses, and effector functions of some immune cells. Pregnancy is also a physiologic state characterized by higher levels of multiple hormones that may impact the effector functions of immune cells, such as progesterone, estrogen, human chorionic gonadotropin, prolactin, and relaxin. Each of these hormones acts to support a tolerogenic immune state of pregnancy, which helps prevent fetal rejection, but may also contribute to an impaired antiviral response. In this review, we address the unique role of adaptive and innate immune cells in the control of pathogenic respiratory viruses and how pregnancy and specific hormones can impact their effector actions. We highlight viruses with sex‐specific differences in infection outcomes and why pregnancy hormones may contribute to fetal protection but aid the virus at the expense of the mother's health.

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“…There are various peer-reviewed reports on the relationship between Coronavirus Disease 2019 (COVID-19), which caused a major pandemic in the world, and adverse pregnancy outcomes [1][2][3]. In recent years, number of research studies on the immune response in COVID-19 cases seen during pregnancy have also been increased [4,5].…”

Section: Introductionmentioning

confidence: 99%

Functional Relationship of Interferon Regulator Factor-5, Interferon-γ, and Hypoxia-Induced Factor-1α with COVID-19 During Pregnancy Outcomes

Herkiloğlu

Gokce

Erdoğan

et al. 2022

Preprint

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Objective: Interferon-gamma (IFN-γ), interferon regulator factor-5 (IRF5), and hypoxia-induced factor-1 Alpha (HIF-1α) are amongst the key immune molecules that function in Coronavirus Disease 2019 (COVID-19). Herein, we aimed to investigate the levels of IFN-γ, IRF5, and HIF-1α in cases who had COVID-19 during their pregnancy.Methods: Thirty-three unvaccinated pregnant women with COVID-19, and 129 unvaccinated healthy pregnant women (control) were included in the study. IRF5, IFN-γ, and HIF-1α levels were investigated in blood samples taken from pregnants and newborns, and in tissue samples of placenta.Results: Mean IRF5 and IFN-γ levels in pregnant women with COVID-19 were significantly lower, whereas mean HIF-1α levels were significantly higher than the controls (p<0.001, for each). In the receiver operating characteristic (ROC) analyses of maternal samples for determination of post-COVID-19 infection; the cutoff value of 2.015 ng/mg protein for IRF5 level had a sensitivity of 81.8% and a specificity of 82.5% [area under the ROC curve (AUC): 0.161; p<0.001; lower bound (LB): 0.08; upper bound (UB): 0.241; confidence interval (CI) 95%)], and the cutoff value of 225.63 pg/mg protein for IFN-γ level had a sensitivity of 81.8% and a specificity of 85.7% (AUC: 0.147; p<0.001; LB:0.08; UB: 0.241; CI 95%).Conclusion: Our findings show that COVID-19 has a significant effect on IRF5, IFN-γ and HIF-1α levels in pregnant women, and thus these levels can be used as a reliable biomarker for the diagnosis of COVID-19 in pregnant women. To the best of our knowledge, the present study is first attempt to evaluate the funational implications of these immunoregulatory biomarkers in pregnant women with COVID-19.

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The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2

Cited by 29 publications

References 79 publications

Midkine—A novel player in cardiovascular diseases

Midkine—A novel player in cardiovascular diseases

Role of hormones in the pregnancy and sex‐specific outcomes to infections with respiratory viruses*

Functional Relationship of Interferon Regulator Factor-5, Interferon-γ, and Hypoxia-Induced Factor-1α with COVID-19 During Pregnancy Outcomes

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