scholarly journals SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

2022 ◽  
Author(s):  
Brenda Martínez-González ◽  
María Eugenia Soria ◽  
Lucia Vazquez-Sirvent ◽  
Cristina Ferrer-Orta ◽  
Rebeca Lobo-Vega ◽  
...  
Keyword(s):  
Severe Disease ◽  
Consensus Sequence ◽  
Three Dimensional ◽  
Point Mutations ◽  
Low Frequency ◽  
Diversity Indices ◽  
Mild Disease ◽  
Coding Regions ◽  
Disease Associations ◽  
Mutant Spectrum

Mutant spectra of RNA viruses are important to understand viral pathogenesis, and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultra-deep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of thirty nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

CLINICAL AND LABORATORY PECULIARITIES OF WHOOPING COUGH IN CHILDREN OF DIFFERENT AGE GROUPS

2020 ◽  
Vol 99 (6) ◽  
pp. 98-104
Author(s):  
I.V. Babachenko ◽  
◽  
Y.V. Nesterova ◽  
N.V. Skripchenko ◽  
◽  
...  
Keyword(s):  
Whooping Cough ◽  
Severe Disease ◽  
Respiratory Rhythm ◽  
Age Groups ◽  
Low Frequency ◽  
Pertussis Infection ◽  
Group 2 ◽  
Sick Children ◽  
Hematological Changes ◽  
Group 1

Objective of the research: to present the clinical and laboratory peculiarities of modern whooping cough in hospitalized children of different ages. Materials and methods: сlinical and laboratory characteristics of whooping cough were analyzed in 88 hospitalized sick children aged 1 month to 18 years in groups of children: group 1 – children under 1 year old; group 2 – children 1–6 years old; group 3 – children 7–17 years old. DNA of causative agents of pertussis infection was isolated by PCR in nasopharyngeal swabs using a commercial kit AmpliSens®Bordetella multi-FL (Moscow). Results: children of group 1 in 90% (n=43) of cases were not vaccinated against whooping cough, severe forms were recorded in 17% (n=8) of children of the 1st year of life, and in 15% (n=7) – due to respiratory rhythm disturbances. The diagnosis was confirmed by PCR in 94% (n=45) of children, leukocytosis with lymphocytosis was detected in 81,5% (n=101). Along with hematological changes typical for whooping cough, 79% (n=38) of patients in the first year of life had thrombocytosis (>400×109/l), which was most pronounced in severe disease course 511,5 [425; 568,5]×109/l vs 421 [347; 505,5]×109/l; p<0,05, which has no tendency to decrease throughout the entire observation period and correlates with the level of leukocytes (rs=0,69; p<0,001). Patients over 7 years old in 88% (n=21) of cases were vaccinated against whooping cough, but 79% (n=27) hemograms had no characteristic changes, which, along with a low frequency of confirmation of the diagnosis by PCR 22% (n=4), made it difficult to diagnose whooping cough. Conclusion: children over 7 years of age may not have characteristic hematological changes and PCR diagnostics are insufficiently effective, which contributes to the spread of whooping cough in family foci.

scholarly journals SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.3-1228
Author(s):  
M. E. Tezcan ◽  
N. Şen ◽  
M. Yilmaz ◽  
Ö. Volkan ◽  
E. Tükel ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Scoring System ◽  
Disease Duration ◽  
Severe Disease ◽  
Smoking History ◽  
Disease Group ◽  
Severity Scoring ◽  
Mild Disease ◽  
Co Morbidity ◽  
Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

A Case Series of SARS-CoV-2 RT-PCR-Positive Hospitalized Infants 60 Days of Age or Younger From 2 New York City Pediatric Emergency Departments

2021 ◽  
Vol 60 (4-5) ◽  
pp. 247-251
Author(s):  
Ameer Hassoun ◽  
Nessy Dahan ◽  
Christopher Kelly
Keyword(s):  
New York ◽  
Case Reports ◽  
Severe Disease ◽  
Case Series ◽  
Pediatric Emergency ◽  
Rt Pcr ◽  
Vulnerable Group ◽  
Mild Disease ◽  
Young Infants ◽  
Novel Coronavirus

The emergence of novel coronavirus disease-2019 poses an unprecedented challenge to pediatricians. While the majority of children experience mild disease, initial case reports on young infants are conflicting. We present a case series of 8 hospitalized infants 60 days of age or younger with coronavirus disease-2019. A quarter of these patients had coinfections (viral or bacterial). None of these infants had severe disease. Continued vigilance in testing this vulnerable group of infants is warranted.

scholarly journals SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

2021 ◽  
Vol 11 (5) ◽  
pp. 431
Author(s):  
Sabine Hofer ◽  
Norbert Hofstätter ◽  
Albert Duschl ◽  
Martin Himly
Keyword(s):  
Risk Factor ◽  
Particle Deposition ◽  
Early Stage ◽  
Severe Disease ◽  
Ambient Air ◽  
Aerosol Deposition ◽  
Pulmonary Involvement ◽  
Mild Disease ◽  
Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

scholarly journals Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience

2021 ◽  
Vol 11 (8) ◽  
pp. 709
Author(s):  
Adamantia Liapikou ◽  
Eleni Tzortzaki ◽  
Georgios Hillas ◽  
Miltiadis Markatos ◽  
Ilias C. Papanikolaou ◽  
...  
Keyword(s):  
Preventive Measures ◽  
Severe Disease ◽  
Hospital Setting ◽  
Guidance Document ◽  
Outpatient Management ◽  
Patient Centered ◽  
Mild Disease ◽  
Novel Coronavirus ◽  
Second Wave ◽  
Close Contacts

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients’ isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

scholarly journals Thromboembolism after COVID-19 vaccine in patients with preexisting thrombocytopenia

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Alessandro Mauriello ◽  
Manuel Scimeca ◽  
Ivano Amelio ◽  
Renato Massoud ◽  
Antonio Novelli ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Exome Sequencing ◽  
Clinical Case ◽  
Severe Disease ◽  
Low Frequency ◽  
Postmortem Examination ◽  
Capillary Leak ◽  
Platelet Factor ◽  
Whole Exome

AbstractWhile vaccination is the single most effective intervention to drastically reduce severe disease and death following SARS-CoV-2 infection, as shown in UK and Israel, some serious concerns have been raised for an unusual adverse drug reaction (ADR), including vaccine-induced immune thrombotic thrombocytopenia (VITT) with concurrent low platelets as well as capillary leak syndrome. In fact, the overall safety of the vaccine is highlighted by the low frequency of ADR considering that in UK, by the early June, 40 million first doses and 29 million second doses have been injected; nonetheless, 390 thrombotic events, including 71 fatal events have been reported. Interestingly, the cases reported low platelet counts with the presence of anti-platelet factor-4 (PF4) antibodies, indicating an abnormal clotting reaction. Here, out of three referred cases, we report a post-vaccine clinical case of fatal thrombosis with postmortem examination and whole exome sequencing (WES) analysis, whose pathogenesis appeared associated to a preexisting condition of thrombocytopenia due to myelodysplasia.

scholarly journals Evolution of a narrow-band spectrum of random surface gravity waves

2003 ◽  
Vol 478 ◽  
pp. 1-10 ◽  
Author(s):  
KRISTIAN B. DYSTHE ◽  
KARSTEN TRULSEN ◽  
HARALD E. KROGSTAD ◽  
HERVÉ SOCQUET-JUGLARD
Keyword(s):  
Three Dimensional ◽  
Low Frequency ◽  
Three Dimensions ◽  
Band Spectrum ◽  
Nls Equation ◽  
Random Surface ◽  
Narrow Bandwidth ◽  
Quasi Stationary State ◽  
The Stability ◽  
Three Dimensional Simulations

Numerical simulations of the evolution of gravity wave spectra of fairly narrow bandwidth have been performed both for two and three dimensions. Simulations using the nonlinear Schrödinger (NLS) equation approximately verify the stability criteria of Alber (1978) in the two-dimensional but not in the three-dimensional case. Using a modified NLS equation (Trulsen et al. 2000) the spectra ‘relax’ towards a quasi-stationary state on a timescale (ε2ω0)−1. In this state the low-frequency face is steepened and the spectral peak is downshifted. The three-dimensional simulations show a power-law behaviour ω−4 on the high-frequency side of the (angularly integrated) spectrum.

scholarly journals 526. Clinical Presenting Characteristics of Pediatric COVID-19 Infection in a Tertiary Care Children’s Hospital in Detroit

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S330-S330
Author(s):  
Jocelyn Y Ang ◽  
Nirupama Kannikeswaran ◽  
Basim Asmar
Keyword(s):  
Mechanical Ventilation ◽  
Severe Disease ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Signs And Symptoms ◽  
Pediatric Emergency ◽  
Study Cohort ◽  
Mild Disease ◽  
Presenting Symptoms ◽  
Patient Disposition

Abstract Background There is limited data regarding the presenting clinical characteristics of COVID-19 in children. Our objective is to describe the clinical presentations and outcomes of COVID-19 infection early in the pandemic at our institution. Methods We performed a retrospective chart review of children up to 18 years who underwent testing for SARS CoV-2 from March 1st to May 10th 2020 at our pediatric emergency department. We abstracted patient’s demographics, clinical presentation, diagnostic studies and patient disposition. We classified the severity of clinical illness based on published criteria. We excluded patients diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Results SARS CoV-2 testing was performed on 481 patients of whom 43 (8.9%) tested positive. Of these, 4 were diagnosed with MIS-C. Data of 39 patients were analyzed. Patients’ demographics, co-morbidities, presenting signs and symptoms and disposition are shown in Table 1. Age range was 47 days – 18 years. Infants representing one third (14/39; 35.9%) of our study cohort. There was equal sex distribution. Asthma or obesity was present in 17 (44%). The most common presenting symptoms included fever, cough, shortness of breath and diarrhea. Chest radiograph showed pneumonia in 12 (30.8%) patients. Two thirds (27/39; 69.2%) were asymptomatic or had mild disease; six patients (15.4%) had severe or critical illness (Figure 1). Nineteen (48%) patients were admitted to the general pediatric service. Eleven (28%) were admitted to the Intensive Care Units (ICU). The characteristics, presenting symptoms and interventions performed in the PICU cohort are shown in Table 2. Half of these patients required mechanical ventilation. There was one death in a 3 month old infant unrelated to SARS CoV-2. Majority of the infants required hospitalization (12/14; 85.7%), including 4 to the PICU (one each for non accidental trauma, ingestion, seizure and pneumonia). Table 1. Patient demographics, signs and symptoms of COVID-19 infection in Children Table 2: PICU patients: Characteristics, Interventions and pharmacotherapy Figure 1: Severity of Ill ness in the study cohort Conclusion Majority (17; 43%) of our children with COVID-19 had a mild disease. Eleven (28%) including 4 infants required critical care; 5 required mechanical ventilation. There was no COVID-19 related mortality. Larger studies are needed to further define the spectrum of COVID- 19 and risk factors associated with severe disease in children. Disclosures All Authors: No reported disclosures

The tumor suppressor p53 regulates its own transcription

1993 ◽  
Vol 13 (6) ◽  
pp. 3415-3423
Author(s):  
A Deffie ◽  
H Wu ◽  
V Reinke ◽  
G Lozano
Keyword(s):  
Consensus Sequence ◽  
Point Mutations ◽  
Direct Interaction ◽  
Mutant P53 ◽  
Tumor Suppressor P53 ◽  
Mobility Shift ◽  
Shift Analysis ◽  
Promoter Deletion Analysis ◽  
Protein Dna Interactions ◽  
Responsive Element

The ability of p53 to suppress transformation correlates with its ability to activate transcription. To identify targets of p53 transactivation, we examined the p53 promoter itself. Northern (RNA) analysis and transient transfection experiments showed that p53 transcriptionally regulated itself. A functionally inactive mutant p53 could not regulate the p53 promoter. Deletion analysis of the p53 promoter delineated sequences between +22 and +67 as being critical for regulation. Electrophoretic mobility shift analysis and methylation interference pinpointed the p53 DNA responsive element. When oligomerized in front of a heterologous minimal promoter, this element was regulated by wild-type p53 and not by mutant p53. Point mutations in the DNA element that eliminated protein-DNA interactions also resulted in a nonresponsive p53 promoter. The DNA element in the p53 promoter responsive to p53 regulation is similar to the p53 consensus sequence. However, we have been unable to detect a direct interaction of p53 with its promoter.

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