Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal ...mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown.
This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality.
Pregnant patients with a polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery.
The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019–associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3–5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257–3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7–43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, −0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001).
Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.
The impact of coronavirus disease 2019 on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal ...death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease.
To describe maternal disease and obstetrical outcomes associated with coronavirus disease 2019 in pregnancy to rapidly inform clinical care.
This is a retrospective study of pregnant patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 6 hospital systems in Washington State between Jan. 21, 2020, and April 17, 2020. Demographics, medical and obstetrical history, and coronavirus disease 2019 encounter data were abstracted from medical records.
A total of 46 pregnant patients with a severe acute respiratory syndrome coronavirus 2 infection were identified from hospital systems capturing 40% of births in Washington State. Nearly all pregnant individuals with a severe acute respiratory syndrome coronavirus 2 infection were symptomatic (93.5%, n=43) and the majority were in their second or third trimester (43.5% n=20 and 50.0% n=23, respectively). Symptoms resolved in a median of 24 days (interquartile range, 13–37). Notably, 7 women were hospitalized (16%) including 1 admitted to the intensive care unit. A total of 6 cases (15%) were categorized as severe coronavirus disease 2019 with nearly all patients being either overweight or obese before pregnancy or with asthma or other comorbidities. Of the 8 deliveries that occurred during the study period, there was 1 preterm birth at 33 weeks’ gestation to improve pulmonary status in a woman with class III obesity, and 1 stillbirth of unknown etiology.
Severe coronavirus disease 2019 developed in approximately 15% of pregnant patients and occurred primarily in overweight or obese women with underlying conditions. Obesity and coronavirus disease 2019 may synergistically increase risk for a medically indicated preterm birth to improve maternal pulmonary status in late pregnancy. These findings support categorizing pregnant patients as a higher-risk group, particularly those with chronic comorbidities.
MDA-5 recognition of a murine norovirus McCartney, Stephen A; Thackray, Larissa B; Gitlin, Leonid ...
PLoS pathogens,
07/2008, Letnik:
4, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from ...research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1. We demonstrate that MDA5-/- dendritic cells(DC) have a defect in cytokine response to MNV-1. In addition, MNV-1 replicates to higher levels in MDA5-/- DCs as well as in MDA5-/- mice in vivo. Interestingly, TLR3-/- DCs do not have a defect in vitro, but TLR3-/- mice have a slight increase in viral titers. This is the first demonstration of an innate immune sensor for norovirus and shows that MDA5 is required for the control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a ...model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood.
This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State.
Pregnant patients with a polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State.
A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3–23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2–7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3–2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3–20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96–1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%).
The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.
Intra-amniotic infection or inflammation is common in early preterm birth and associated with substantial neonatal lung morbidity owing to fetal exposure to proinflammatory cytokines and infectious ...organisms. Amniotic fluid interleukin 8, a proinflammatory cytokine, was previously correlated with the development of neonatal bronchopulmonary dysplasia, but whether amniotic fluid cytokines or placental pathology more accurately predicts neonatal lung pathology and morbidity is unknown. We have used a pregnant nonhuman primate model of group B Streptococcus infection to study the pathogenesis of intra-amniotic infection, bacterial invasion of the amniotic cavity and fetus, and microbial-host interactions. In this nonhuman primate model, we have studied the pathogenesis of group B Streptococcus strains with differing potential for virulence, which has resulted in a spectrum of intra-amniotic infection and fetal lung injury that affords the opportunity to study the inflammatory predictors of fetal lung pathology and injury.
This study aimed to determine whether fetal lung injury is best predicted by placental histopathology or the cytokine response in amniotic fluid or maternal plasma.
Chronically catheterized pregnant monkeys (Macaca nemestrina, pigtail macaque) at 116 to 125 days gestation (term at 172 days) received a choriodecidual inoculation of saline (n=5), weakly hemolytic group B Streptococcus strain (n=5, low virulence), or hyperhemolytic group B Streptococcus strain (n=5, high virulence). Adverse pregnancy outcomes were defined as either preterm labor, microbial invasion of the amniotic cavity, or development of the fetal inflammatory response syndrome. Amniotic fluid and maternal and fetal plasma samples were collected after inoculation, and proinflammatory cytokines (tumor necrosis factor alpha, interleukin beta, interleukin 6, interleukin 8) were measured by a multiplex assay. Cesarean delivery was performed at the time of preterm labor or within 1 week of inoculation. Fetal necropsy was performed at the time of delivery. Placental pathology was scored in a blinded fashion by a pediatric pathologist, and fetal lung injury was determined by a semiquantitative score from histopathology evaluating inflammatory infiltrate, necrosis, tissue thickening, or collapse scored by a veterinary pathologist.
The principal findings in our study are as follows: (1) adverse pregnancy outcomes occurred more frequently in animals receiving hyperhemolytic group B Streptococcus (80% with preterm labor, 80% with fetal inflammatory response syndrome) than in animals receiving weakly hemolytic group B Streptococcus (40% with preterm labor, 20% with fetal inflammatory response syndrome) and in controls (0% preterm labor, 0% fetal inflammatory response syndrome); (2) despite differences in the rate of adverse pregnancy outcomes and fetal inflammatory response syndrome, fetal lung injury scores were similar between animals receiving the weakly hemolytic group B Streptococcus strains and animals receiving the hyperhemolytic group B Streptococcus strains; (3) fetal lung injury score was significantly correlated with peak amniotic fluid cytokines interleukin 6 and interleukin 8 but not tumor necrosis factor alpha or interleukin 1 beta; and (4) fetal lung scores were poorly correlated with maternal and fetal plasma cytokine levels and placental pathology.
Amniotic fluid interleukin 6 and interleukin 8 levels were superior predictors of fetal lung injury than placental histopathology or maternal plasma cytokines. This evidence supports a role for amniocentesis in the prediction of neonatal lung morbidity owing to intra-amniotic infection, which cannot be provided by cytokine analysis of maternal plasma or placental histopathology.
Innate sensors of viral infection detect viral products and initiate the signal cascades that lead to the antiviral response. Several proteins have been identified to play a role in this process, ...mostly members of the Toll‐like receptor and retinoic acid‐inducible gene I‐like receptor families. These receptors have been demonstrated to function in part by recognizing a diverse yet unique repertoire of nucleic acid substrates. Upon recognition of their ligands, these sensors activate distinct signaling pathways that lead to the secretion of type I interferon and inflammatory cytokines. It remains to be seen, however, if these sensors are redundant or whether each serves a unique function. In this work, we review the current knowledge of viral sensors, speculate on how they may function in vivo, and explore the potential reasons for their diversity.
Review on the cellular and molecular sources of IFN‐I during virus infections with emphasis on plasmacytoid dendritic cells (pDC) and dsRNA sensors.
IFN‐I are pleiotropic cytokines that impact innate ...and adaptive immune responses. In this article, we discuss TLR7/9 versus TLR3/MDA5 signaling in antiviral responses and diabetes. pDCs are thought to have a critical role in antiviral defense because of their ability to rapidly secrete large amounts of IFN‐I through TLR7/9 signaling. A recent study demonstrates that although pDCs are a source of IFN‐I in vivo, their overall contribution to viral containment is limited and time‐dependent, such that additional cellular sources of IFN‐I are required to fully control viral infections. dsRNA sensors, such as TLR3 and MDA5, provide another important trigger for antiviral IFN‐I responses, which can be exploited to enhance immune responses to vaccines. In the absence of infection, IFN‐I production by pDCs or from signaling through dsRNA sensors has been implicated in the pathogenesis of autoimmune diseases such as diabetes. However, recent data demonstrate that IFN‐I production via TLR3 and MDA5 is critical to counter diabetes caused by a virus with preferential tropism for pancreatic β‐cells. This highlights the complexity of the host antiviral response and how multiple cellular and molecular components balance protective versus pathological responses.
The innate immune system detects viruses through molecular sensors that trigger the production of type I interferons (IFN‐I) and inflammatory cytokines. As viruses vary tremendously in size, ...structure, genomic composition, and tissue tropism, multiple sensors are required to detect their presence in various cell types and tissues. In this review, we summarize current knowledge of the diversity, specificity, and signaling pathways downstream of viral sensors and ask whether two distinct sensors that recognize the same viral component are complementary, compensatory, or simply redundant. We also discuss why viral sensors are differentially distributed in distinct cell types and whether a particular cell type dominates the IFN‐I response during viral infection. Finally, we review evidence suggesting that inappropriate signaling through viral sensors may induce autoimmunity. The picture emerging from these studies is that disparate viral sensors in different cell types form a dynamic and integrated molecular network that can be exploited for improving vaccination and therapeutic strategies for infectious and autoimmune diseases.
Problem
Preeclampsia (PE) is associated with an increased risk of maternal cardiovascular disease (CVD), however, it is unclear whether this is due to shared underlying physiology or changes which ...occur during the disease process. Fetal microchimerism (FMc) within the maternal circulation can durably persist decades after pregnancy, is known to occur at greater frequency in PE, and can potentially affect local and systemic immune programming, thus changes in cellular FMc may provide a mechanism for long‐term health outcomes associated with PE.
Method of study
We investigated whether PE is associated with alterations in FMc immune and stem cell populations. We analyzed maternal peripheral blood mononuclear cells (PBMC) from PE cases (n = 16) and matched controls from normal pregnancies (n = 16), from which immune and stem cell subsets were isolated by flow cytometry. Genomic DNA was extracted from total PMBC and individual cell subsets, and FMc frequency was quantified by quantitative polymerase chain reaction assays targeting a fetal‐specific non‐shared polymorphism identified from family genotyping.
Results
There was a significant increase in FMc concentration in immune cell subsets in PE cases compared to controls, predominantly in B cell, and NK cell lymphocyte populations. There was no significant difference in FMc frequency or concentration within the stem cell population between PE and controls.
Conclusions
The altered concentrations of immune cells within FMc in the maternal blood provides a potential mechanism for the inflammation which occurs during PE to induce long‐lasting changes to the maternal immune system and may potentially promote chronic maternal disease.
The ongoing coronavirus disease 2019 (COVID‐19) pandemic has led to a global public health emergency with the need to identify vulnerable populations who may benefit from increased screening and ...healthcare resources. Initial data suggest that overall, pregnancy is not a significant risk factor for severe coronavirus disease 2019 (COVID‐19). However, case series have suggested that maternal obesity is one of the most important comorbidities associated with more severe disease. In obese individuals, suppressors of cytokine signaling are upregulated and type I and III interferon responses are delayed and blunted leading to ineffective viral clearance. Obesity is also associated with changes in systemic immunity involving a wide range of immune cells and mechanisms that lead to low‐grade chronic inflammation, which can compromise antiviral immunity. Macrophage activation in adipose tissue can produce low levels of pro‐inflammatory cytokines (TNF‐α, IL‐1β, IL‐6). Further, adipocyte secretion of leptin is pro‐inflammatory and high circulating levels of leptin have been associated with mortality in patients with acute respiratory distress syndrome. The synergistic effects of obesity‐associated delays in immune control of COVID‐19 with mechanical stress of increased adipose tissue may contribute to a greater risk of pulmonary compromise in obese pregnant women. In this review, we bring together data regarding obesity as a key co‐morbidity for COVID‐19 in pregnancy with known changes in the antiviral immune response associated with obesity. We also describe how the global burden of obesity among reproductive age women has serious public health implications for COVID‐19.
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