Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.
Project description:It is poorly understood how maternal covid-19 results in severe placental disorders. Single nuclei sequencing (sci-rna-seq3) was used to profle transcriptomic changes in the human placenta in response to maternal COVID-19.
Project description:We utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. Our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.
Project description:Although some studies reported the comprehensive mRNA expression analysis of coronavirus disease 2019 (COVID-19) using blood samples to understand its pathogenesis, the characteristics of RNA expression in COVID-19 and sepsis have not been compared. We compared the transcriptome expression of whole blood samples from patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with sepsis caused by other bacteria who entered the intensive care unit to clarify the COVID-19-specific RNA expression and understand its pathogenesis. Transcriptomes related to mitochondria were upregulated in COVID-19, whereas those related to neutrophils were upregulated in sepsis. However, the transcriptomes related to neutrophils were upregulated in both COVID-19 and sepsis compared to in healthy controls, whereas the mitochondrial transcriptomes were upregulated in COVID-19 and downregulated in sepsis compared to in healthy controls. Moreover, sepsis showed sub-optimal intrinsic apoptotic features compared with COVID-19. The transcriptome expression of COVID-19 has been examined in vitro but has not been widely validated using human specimens. This study improves the understanding of the pathogenesis of COVID-19 and can contribute to the development of treatments.
Project description:An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room (ER) arrival, monocytes showed decreased surface molecules expression, including HLA-DR, in association to an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. These alterations were mostly normalized in post-COVID-19 patients, 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory, tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface markers and low IRF1 gene transcription in circulating monocytes at ER defined a COVID-19 patients group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patients stratification and to designing innate immunity-focused therapies.
Project description:Whole transcriptome analysis performed on lung samples from dead covid-19 patients and healthy non-covid-19 individuals of multiple age groups.
Project description:The SARS-CoV-2 has already caused over 523 million COVID-19 cases and 6.27 million deaths worldwide. COVID-19 leads to a severe acute respiratory syndrome, a hyperinflammatory response, and widespread multi-organ damage. Common symptoms of COVID-19 include fever, cough, fatigue, shortness of breath, and loss of taste and smell. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2. We performed RNA-seq analysis of lung tissues from three COVID-19 patients.
Project description:Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues.
Project description:Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA-Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups.
Project description:The COVID-19 pandemic affected millions of pregnant persons, yet the consequences of maternal SARS-CoV-2 infection on the placental function and the fetal health remain poorly characterized. While inflammatory and structural alterations have been described in placentas from exposed pregnancies, the underlying molecular mechanisms are still unclear. The aim of this study was to evaluate transcriptomic alterations in placentas exposed to maternal SARS-CoV-2 infection (COVID+) compared to unexposed placentas (COVID-). We analyzed 67 placentas collected between March 2020 and June 2021 from singleton pregnancies with (n = 41) or without (n = 26) a history of maternal SARS-CoV-2 infection during pregnancy. Demographic, obstetric, placental, and fetal data were extracted from the medical records. SARS-CoV-2 RNA was not detected in any placental sample. Bulk RNA-sequencing was performed on villous biopsies preserved either frozen or in RNALater. Global transcriptomic analysis comparing COVID+ and COVID- placentas revealed an upregulation of genes involved in cytoskeleton organization. Stratified analysis by fetal sex identified a marked sex-specific response, with 43 differentially expressed genes (DEGs) in placenta from female fetuses (XX) in the COVID+ group compared to COVID-, whereas only one DEG was identified in placenta from male fetuses (XY). In XX COVID+ placentas, pathways related to cytoskeleton organization, pregnancy specific processes, and muscle development were altered. These results highlight a sex-specific dysregulation of placental gene expression following maternal SAR-CoV-2 infection, predominantly affecting placentas from female fetuses.