Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Journal of Microbiology ; 60(9):867-876, 2022.
Article in English | MEDLINE | ID: covidwho-1999733

ABSTRACT

RNA modifications are a common occurrence across all domains of life. Several chemical modifications, including N6-methyladenosine, have also been found in viral transcripts and viral RNA genomes. Some of the modifications increase the viral replication efficiency while also helping the virus to evade the host immune system. Nonetheless, there are numerous examples in which the host's RNA modification enzymes function as antiviral factors. Although established methods like MeRIP-seq and miCLIP can provide a transcriptome- wide overview of how viral RNA is modified, it is difficult to distinguish between the complex overlapping viral transcript isoforms using the short read-based techniques. Nanopore direct RNA sequencing (DRS) provides both long reads and direct signal readings, which may carry information about the modifications. Here, we describe a refined protocol for analyzing the RNA modifications in viral transcriptomes using nanopore technology.

2.
Archiv Euromedica ; 12(4):6, 2022.
Article in English | Web of Science | ID: covidwho-1979989

ABSTRACT

One of the current problems of modern obstetrics is the diagnosis, treatment and prevention of intrauterine growth retardation. This pathology ranks second after prematurity among the causes of low=birth-weight babies. The prevalence of fetal retardation varies worldwide from 6.5 to 30.0% of all births, of which about 23% are very low birthweight and about 38% extremely low birthweight babies. A new coronavirus infection, caused by the viral pathogen SARS-CoV-2, which contributes to thrombotic microangiopathy in combination with hypercoagulation syndrome, is currently ongoing. During physiological pregnancy, there is known to be an increased risk of complications associated with both bleeding and thrombosis, which are affected by changes in fibrinolytic activity and hypercoagulable state, endothelial dysfunction, and changes in blood rheological properties. It significantly increases the risk of pregnancy complications such as pre-eclampsia, placental insufficiency, fetal hypoxia, and therefore leads to intrauterine growth retardation of the fetus. This study analyzed the status of newborn babies and the incidence of intrauterine growth retardation in women who had contracted coronavirus infection. Two groups of women were included in study: the first included those who became pregnant 3 to 6 months after a new coronavirus infection, and the second was a control group. The study found that women in the first group were more likely to have pre-eclampsia and their babies were more likely to be diagnosed with intrauterine growth retardation.

3.
American Journal of Respiratory and Critical Care Medicine ; 205:2, 2022.
Article in English | English Web of Science | ID: covidwho-1880891
4.
Topics in Antiviral Medicine ; 30(1 SUPPL):37-38, 2022.
Article in English | EMBASE | ID: covidwho-1880239

ABSTRACT

Background: Post-Acute Sequelae of SARS-CoV-2 (PASC) is characterized by persistent symptoms negatively impacting quality of life several weeks after SARS-CoV-2 diagnosis. Proposed risk factors include older age, female sex, comorbidities, and severe COVID-19, including hospitalization and oxygen requirement. Yet, associations of these factors with prolonged symptoms remain poorly understood globally. Methods: The global, observational cohort study HVTN 405/HPTN 1901 characterizes the clinical and immunologic course in the first year after SARS-CoV-2 infection among adults. The cohort was categorized by infection severity (asymptomatic;symptomatic with no oxygen requirement [NOR];non-invasive oxygen requirement [NIOR];or invasive oxygen requirement [IOR]). A regression model was applied to estimate geometric mean ratios (GMR) for duration and odds ratios (OR) for persistence of symptoms. Results: 759 participants from Peru (25.2%), USA (26.0%), Republic of South Africa (RSA, 37.7%), and non-RSA Sub-Saharan Africa (11.2%) were enrolled a median of 51 (IQR 35-66) days post-diagnosis, from May 2020 to Mar 2021. 53.8% were female, 69.8% were <55yo (median 44yo, IQR 33-58) and identified as non-Hispanic Black (42.7%), Hispanic (27.9%) or non-Hispanic White (15.8%). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), HIV infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR 47.4%;NIOR 22.9%;and IOR 5.8%). Among symptomatic participants, median acute COVID-19 duration was 20 days (IQR 11-35);43.3% had ≥1 persistent symptom after COVID-19 resolution (39.8% NOR;49.1 % NIOR+IOR;p=0.037);16.8% reported ≥1 symptom >42 days (14.0% NOR;21.6% NIOR+IOR;p=0.025). Symptom duration was not associated with age or sex assigned at birth but was associated with disease severity (GMR 2.09;95%CI 1.5-2.91, p<0.001 for NIOR vs NOR;not significant for IOR vs NIOR), lung disease (GMR 2.43;95%CI 1.42-4.16, p=0.001), and global region (p<0.05, see Figure 1). Prolonged viral shedding was associated with persistent diarrhea (OR 6.59;95%CI 1.65-26.86;p=0.008). Conclusion: A recovery course consistent with PASC was significantly associated with infection severity, lung disease, and region. Regional differences in symptom profiles and duration may be influenced by viral diversity, genetic, or cultural factors and likely reflect disparities in healthcare access and interventions. Better understanding PASC associations may improve clinical assessment and management globally.

5.
CHEST ; 161(1):A282-A282, 2022.
Article in English | Academic Search Complete | ID: covidwho-1634905
6.
Chest ; 160(4):A520, 2021.
Article in English | EMBASE | ID: covidwho-1457765

ABSTRACT

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: SARS-CoV-2 is a highly contagious respiratory virus associated with significant morbidity and mortality in the acute phase. It is also associated with long-term morbidity in a subset of patients. It is not clear which patients will have persistent symptoms. SARS-CoV-2 affects the pulmonary vasculature. We hypothesize that differences in blood volume measurements on CT of the chest during the acute phase are associated with significant dyspnea after the acute phase. METHODS: We retrospectively studied subjects hospitalized for COVID-19 pneumonia who had an initial and follow-up CT chest, pulmonary function tests (PFTs), 6-minute walk test (6MWT), and a clinical assessment in our post-COVID-19 clinic. We excluded subjects with pre-existing lung disease based on prior PFTs. Serum inflammatory biomarkers, CT scan, and clinical characteristics were assessed during the hospitalization. CT images were evaluated by Functional Respiratory Imaging (deep learning trained) with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm2 (BV5), 5-10mm2 (BV5_10), and ≥10mm2 (BV10) in cross-sectional area were analyzed. Additionally, the amount of opacification on CT (i.e., ground-glass opacities, crazy paving, reticular disease and edema) was quantified in each patient. PFTs were performed <3 months after discharge. We defined a modified Medical Research Council (mMRC) score≥2 as having significant dyspnea. We compared subjects with an mMRC score≥2 to those with an mMRC score<2. BV measures were also compared to a historical cohort of healthy controls. RESULTS: 50 subjects were included. 22 had mMRC score≥2. The groups had similar baseline characteristics. Admission hemoglobin, peak inflammatory biomarkers, and follow-up PFTs were similar between groups. On 6MWT, there were no differences between groups in resting SpO2, lowest SpO2, or walk distance. On admission CT, percent BV5 was lower, and percents BV5_10 and BV10 were higher in the mMRC≥2 group compared to the mMRC<2 group. All BV measures in both groups were different compared to healthy controls. At follow-up, BV5 measures in the mMRC≥2 group improved but remained abnormal compared to healthy controls, without a statistical difference compared to the mMRC<2 group. Opacification was similar between groups on admission and follow-up CTs. CONCLUSIONS: Despite similar baseline characteristics, lung function, degree of opacification and oxygenation, persistent dyspnea after COVID-19 pneumonia is related to pruning of the small pulmonary vessels (BV5) during the acute phase and not to differences in vascular abnormalities seen in short term follow-up. CLINICAL IMPLICATIONS: Identification of markers of persistent dyspnea in post-acute COVID-19 contributes to a better understanding of the natural course and prognosis of the disease. This will impact research and patient care in the near future. DISCLOSURES: No relevant relationships by Melinda Darnell, source=Web Response Owner/Founder relationship with Fluidda Please note: $20001 - $100000 by Jan De Backer, source=Web Response, value=Ownership interest No relevant relationships by Derlis Fleitas Sosa, source=Web Response No relevant relationships by Victor Kim, source=Web Response Employee relationship with FLUIDDA Please note: 02/01/2017 - Present Added 04/26/2021 by Maarten Lanclus, source=Web Response, value=Salary No relevant relationships by Ifeoma Oriaku, source=Web Response No relevant relationships by Daniel Salerno, source=Web Response

8.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277775

ABSTRACT

Rationale: Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and computed tomography (CT) scan parameters at the time of infection would be associated with abnormal gas exchange at short term follow-up.Methods: We studied subjects who were hospitalized for COVID-19 pneumonia and then discharged. Those with pre-existing lung disease (except asthma) or reduced diffusing capacity for carbon monoxide (DLCO) prior to COVID-19 infection were excluded. Information on serum inflammatory biomarkers, CT scan, and clinical characteristics were collected in the index hospitalization. Pulmonary function tests and 6-minute walk tests were assessed at 2-3 months after discharge. CT images at the time of hospitalization were evaluated by Functional Respiratory Imaging (FRI;FLUIDDA, Inc., Antwerp, Belgium) with 3D reconstruction of the lungs and pulmonary vasculature to analyze pulmonary blood volume. Blood volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5-10), and ≥10mm (BV10) in cross-sectional area were analyzed. Additionally, the amount of inflammation on CT (ground-glass opacities) was quantified. We divided subjects into those with a DLCO <80% predicted and those with a DLCO ≥80% predicted based on follow-up pulmonary function tests. Results: 38 subjects were included in our cohort. Pulmonary function tests were performed 76.5±35.1 days after the first day of hospitalization. The results are summarized in the Table. 31 out of 38 (81.5%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, and smoking status. Peak D-dimer, LDH, and ferritin levels were greater in the DLCO<80% group. Spirometric measures and lung volumes were similar between groups. Inflammation was not different between groups, but BV5-10 and BV10 measures were higher in the DLCO<80% group. BV5-10 was associated with DLCO<80% in multivariable logistic regression with demographics, smoking status, lung volumes, and hemoglobin as covariates (OR 1.29, 95% CI 1.01, 1.64).Conclusions: Higher peak D-dimer levels at the time of hospitalization and abnormalities in pulmonary blood volumes are associated with a reduced DLCO at follow-up. These findings suggest that pulmonary vascular and coagulation abnormalities during hospitalization with COVID-19 might have long-lasting effects on pulmonary function. Further study regarding the influence of pulmonary blood volumes and measures of abnormal coagulation on short term COVID-19 outcomes is warranted.

9.
Mol Cell ; 81(13): 2838-2850.e6, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1202181

ABSTRACT

SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs, including ZC3HAV1, TRIM25, PARP12, and SHFL, and 8 proviral RBPs, such as EIF3D and CSDE1, which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.


Subject(s)
Autoantigens/genetics , COVID-19/genetics , RNA, Viral/genetics , Ribonucleoproteins/genetics , SARS-CoV-2/genetics , COVID-19/virology , Coronavirus OC43, Human/genetics , Coronavirus OC43, Human/pathogenicity , HEK293 Cells , Host-Pathogen Interactions/genetics , Humans , Protein Binding/genetics , Protein Interaction Maps/genetics , RNA-Binding Proteins/genetics , SARS-CoV-2/pathogenicity , TOR Serine-Threonine Kinases/genetics , Transcription Factors/genetics , Transcriptome/genetics , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Virus Replication/genetics
10.
Experimental Neurobiology ; 29(5):402, 2020.
Article in English | Scopus | ID: covidwho-972056

ABSTRACT

We would like to correct author’s affiliations, add an author and an edit one sentence as shown below. 1) The corrected affiliations (switch affiliation 1 and 2) and added author are marked by bold and underlines. Joungha Won1,2, Solji Lee2, Myungsun Park2, Tai Young Kim2, Mingu Gordon Park2,3, Byung Yoon Choi4, Dongwan Kim5,6, Hyeshik Chang5,6, Won Do Heo1, V. Narry Kim5,6 and C. Justin Lee2* 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, 2Center for Cognition and Sociality, Cognitive Glioscience Group, Institute for Basic Science, Daejeon 34126, 3KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, 4Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam 13620, 5Center for RNA Research, Institute for Basic Science, Seoul 08826, 6School of Biological Sciences, Seoul National University, Seoul 08826, Korea 2) In Quantitative rtPCR section (Page 110, in material and methods) we would like to correct the following sentence from;“In brief, each reaction buffer consisted of a total volume of 20 µl containing 8 µl of 100 µM forward and reverse primers (4 µl for each primer), 2 µl of cDNA, and 10 µl power SYBR Green PCR Master Mix.” to;“In brief, each reaction buffer consisted of a total volume of 20 µl containing 2 µl of 10 µM forward and reverse primers (1 µl for each primer), 2 µl of cDNA, and 10 µl power SYBR Green PCR Master Mix”. © 2020 Korean Society for Neurodegenerative Disease. All rights reserved.

11.
Cell ; 181(4): 914-921.e10, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-108856

ABSTRACT

SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.


Subject(s)
Betacoronavirus/genetics , RNA, Viral/genetics , Transcriptome , Animals , Chlorocebus aethiops , Epigenesis, Genetic , RNA Processing, Post-Transcriptional , SARS-CoV-2 , Sequence Analysis, RNA , Vero Cells
12.
Exp Neurobiol ; 29(2): 107-119, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-6809

ABSTRACT

The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person-to-person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizol-based RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.

SELECTION OF CITATIONS
SEARCH DETAIL