scholarly journals Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

BMJ ◽  
2020 ◽  
pp. m1443 ◽  
Author(s):  
Shufa Zheng ◽  
Jian Fan ◽  
Fei Yu ◽  
Baihuan Feng ◽  
Bin Lou ◽  
...  
Keyword(s):  
Viral Load ◽  
Retrospective Cohort ◽  
Severe Disease ◽  
Zhejiang Province ◽  
Serum Samples ◽  
Viral Loads ◽  
Mild Disease ◽  
Stool Samples ◽  
Serum And Urine ◽  
Serum And Urine Samples

AbstractObjectiveTo evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China.DesignRetrospective cohort study.SettingA designated hospital for patients with covid-19 in Zhejiang province, China.Participants96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020.Main outcome measuresRibonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.Results3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients.ConclusionThe duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.

1329 Can One Size Fit All: Is Laparoscopic Roux-En-Y Gastric Bypass the Best Bariatric Procedure for Treating Type 2 Diabetes Mellitus (T2DM)?

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
V Mahendran ◽  
P Ricart ◽  
S Robinson ◽  
A Perry ◽  
M Wadley
Keyword(s):  
Bariatric Surgery ◽  
Gastric Bypass ◽  
Retrospective Cohort ◽  
Severe Disease ◽  
Morbidly Obese ◽  
Disease Remission ◽  
Mild Disease ◽  
Moderate Disease ◽  
Remission Rates

Abstract Introduction Bariatric surgery produces superior weight loss and reversal of comorbidities in morbidly obese individuals compared to medical therapy alone. Laparoscopic Roux-en-Y gastric bypass (LRYGB) was traditionally considered to prolonged remission of T2DM compared to other procedures such as Laparoscopic Sleeve-Gastrectomy (LSG). But recently published studies seek to disprove this by emphasising on duration and severity of T2DM before surgery rather than the type of procedure. We aim to verify if the severity of T2DM and type of operation (LRYGB Vs LSG) influence remission rates. Method In this retrospective cohort study, 204 patients were diagnosed with T2DM pre-operatively and had undergone either LRYGB or LSG. We used the Individualised Metabolic Surgery Score (IMSS) tool to divide patients into mild, moderate, and severe categories. Results Results showed that of the 204 patients 15% (n = 31) had mild disease, 62%( n = 127) had moderate disease and 23% (n = 46) had severe disease. Remission rates in each category were as follows: Conclusions We agree that patients with longstanding and severe T2DM have low remission rates after bariatric surgery, probably due to diminished beta-cell reserve. It is in contrary to recent publications which recommend LSG over LRYGB in patients with severe disease. This evidence necessitates further prospective studies before deciding which is the best procedure for patients with severe and longstanding T2DM.

scholarly journals SARS-CoV-2 Persistence in Immunocompromised Children

2021 ◽  
Author(s):  
Susan Dolan ◽  
Jean Mulcahy Levy ◽  
Angla Moss ◽  
Kelly Pearce ◽  
Samuel Dominguez ◽  
...  
Keyword(s):  
Viral Load ◽  
Median Time ◽  
Immunosuppressive Treatment ◽  
Viral Persistence ◽  
High Viral Load ◽  
Viral Loads ◽  
Mild Disease ◽  
Kaplan Meier ◽  
Diagnostic Panel ◽  
Event Times

Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

Addressing the standardisation of internal standards and preservative used in human bio fluids for NMR analysis: a method optimization

2021 ◽  
Vol 36 (3) ◽  
pp. 189-197
Author(s):  
Fatimatuzzahra’ Abd Aziz ◽  
Baharudin Ibrahim ◽  
Vikneswaran Murugaiyah ◽  
Azmi Sarriff
Keyword(s):  
Human Subjects ◽  
Internal Standard ◽  
Extended Period ◽  
Urine Samples ◽  
Nmr Analysis ◽  
Serum Samples ◽  
Healthy Human ◽  
Considerable Saving ◽  
Serum And Urine ◽  
Serum And Urine Samples

Abstract Objectives A database comprising multivariate data in developing a model from nuclear magnetic resonance (NMR) analysis using human bio fluids are necessary to have reproducibility and reliability of the data. To achieve reproducibility of the data, standardised experiments, including internal standard and preservative used should be attained, especially for samples such as human bio fluids to hinder the variation among samples. The aim of the study was to optimise in commonly used human bio fluids (serum and urine) for a suitable internal standard and preservative used in extended storage samples for NMR analysis. Methods Serum and urine samples were collected from healthy human subjects. The experiment was divided into two parts, part one to evaluate 2,2,2,2-tetradeutero-4,4-dimethyl-4-silapentanoic acid (TSP) and 4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA) as the optimal internal standard for the serum and urine samples. The second part investigated the effects of preservatives in the serum and urine samples on extended storage. Results Overall, TSP and DSA are suitable to be used as an internal standard in human urine samples. However, DSA is a superior internal standard in serum samples for NMR analysis. For the effect of preservative, the results indicated that human serum and urine samples could be stored without addition of preservative in −80 °C, as no changes in NMR fingerprinting have been observed during storage in the absence or presence of the preservative. Conclusions The findings suggest the use of DSA and TSP as an internal standard in serum and urine samples, respectively. Storage of serum and urine samples without any addition of preservative for an extended period has no effect on the metabolites changes. By having a standardised method, it will offer a considerable saving in both operator and spectrometer time and most importantly produce reproducible and reliable data.

scholarly journals Characterization of the Immune Response during Infection Caused by Clostridioides difficile

2019 ◽  
Vol 7 (10) ◽  
pp. 435 ◽  
Author(s):  
Hamo ◽  
Azrad ◽  
Nitzan ◽  
Peretz
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Interferon Α ◽  
T Helper 1 ◽  
Serum Samples ◽  
Mild Disease ◽  
Clostridioides Difficile ◽  
Cytokines And Chemokines ◽  
Clostridioides Difficile Infection ◽  
Macrophage Colony

The high risk of complications and death following Clostridioides difficile infection (CDI) requires identifying patients with severe disease and treating them accordingly. We characterized the immune response of CDI patients in relation to infection severity. Concentrations of 28 cytokines and chemokines were measured in serum samples, obtained from 54 CDI patients within a median timeframe of 24–48 h after laboratory confirmation of C. difficile infection. Demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined by “Score indices for Clostridioides difficile infection severity”. Of 54 patients (mean age, 76.6 years, 61.1% female), 38 (70.4%) had mild disease and 16 (29.6%) had moderate disease. Seven cytokines were associated with a more severe CDI: granulocyte-macrophage colony-stimulating factor (p = 0.0106), interleukin (IL)-1β (p = 0.004), IL-8 (p = 0.0098), IL-12p70 (p = 0.0118), interferon-α (p = 0.0282), IL-15 (p = 0.0015), and IL-2 (p = 0.0031). Additionally, there was an increased T-helper 1 response in more severe cases of CDI. Cytokines may serve as biomarkers for early prediction of CDI severity. Better and earlier assessment of illness severity will contribute to the adjustment of medical treatment, including monitoring and follow-up.

scholarly journals SARS-CoV-2 viral load is associated with increased disease severity and mortality

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jesse Fajnzylber ◽  
◽  
James Regan ◽  
Kendyll Coxen ◽  
Heather Corry ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Diverse Range ◽  
Viral Loads ◽  
Mild Disease ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Absolute Lymphocyte Counts

Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

scholarly journals Systematic review and patient-level meta-analysis of SARS-CoV-2 viral dynamics to model response to antiviral therapies

2020 ◽  
Author(s):  
Silke Gastine ◽  
Juanita Pang ◽  
Florencia A.T. Boshier ◽  
Simon J Carter ◽  
Dagan O. Lonsdale ◽  
...  
Keyword(s):  
Systematic Review ◽  
Viral Load ◽  
Case Reports ◽  
Meta Analysis ◽  
Severe Disease ◽  
Case Series ◽  
Viral Clearance ◽  
Viral Dynamics ◽  
Viral Loads ◽  
Patient Level

Background: SARS-CoV-2 viral loads change rapidly following symptom onset so to assess antivirals it is important to understand the natural history and patient factors influencing this. We undertook an individual patient-level meta-analysis of SARS-CoV-2 viral dynamics in humans to describe viral dynamics and estimate the effects of antivirals used to-date. Methods: This systematic review identified case reports, case series and clinical trial data from publications between 1/1/2020 and 31/5/2020 following PRISMA guidelines. A multivariable Cox proportional hazards regression model (Cox-PH) of time to viral clearance was fitted to respiratory and stool samples. A simplified four parameter nonlinear mixed-effects (NLME) model was fitted to viral load trajectories in all sampling sites and covariate modelling of respiratory viral dynamics was performed to quantify time dependent drug effects. Findings: Patient-level data from 645 individuals (age 1 month-100 years) with 6316 viral loads were extracted. Model-based simulations of viral load trajectories in samples from the upper and lower respiratory tract, stool, blood, urine, ocular secretions and breast milk were generated. Cox-PH modelling showed longer time to viral clearance in older patients, males and those with more severe disease. Remdesivir was associated with faster viral clearance (adjusted hazard ratio (AHR) = 9.19, p<0.001), as well as interferon, particularly when combined with ribavirin (AHR = 2.2, p=0.015; AHR = 6.04, p = 0.006). Interpretation: Combination therapy including interferons should be further investigated. A NLME model for designing and analysing viral pharmacodynamics in trials has been established.

scholarly journals COVID-19 Viral Load Not Associated with Disease Severity: Findings from A Retrospective Cohort Study

2021 ◽  
Author(s):  
Abdulkarim Abdulrahman ◽  
Saad Mallah ◽  
Manaf AlQahtani
Keyword(s):  
Cohort Study ◽  
Viral Load ◽  
Disease Severity ◽  
Odds Ratio ◽  
Retrospective Cohort ◽  
Statistical Significance ◽  
Rt Pcr ◽  
Cross Sectional ◽  
Viral Loads ◽  
Using Data

Abstract Background: Being able to use COVID-19 RT-PCR Ct values as simple markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study’s objective was thus to assess whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices Results: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain’s National COVID-19 Task force’s centralised database. The study period was from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p=0.054). Conclusion: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder.

scholarly journals SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus

2020 ◽  
Vol 5 ◽  
pp. 181
Author(s):  
Monique I. Andersson ◽  
Carolina V. Arancibia-Carcamo ◽  
Kathryn Auckland ◽  
J. Kenneth Baillie ◽  
Eleanor Barnes ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Severe Disease ◽  
Acute Infection ◽  
Laboratory Diagnosis ◽  
Blood Products ◽  
Rt Pcr ◽  
Serum Samples ◽  
Blood Samples ◽  
Viral Loads ◽  
Clinical Cohort

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.

scholarly journals Rotavirus A in Brazil: Molecular Epidemiology and Surveillance during 2018–2019

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 515 ◽  
Author(s):  
Meylin Bautista Gutierrez ◽  
Alexandre Madi Fialho ◽  
Adriana Gonçalves Maranhão ◽  
Fábio Correia Malta ◽  
Juliana da Silva Ribeiro de Andrade ◽  
...  
Keyword(s):  
Viral Load ◽  
Severe Disease ◽  
Emergency Department Visits ◽  
Childhood Mortality ◽  
Epidemiological Surveillance ◽  
Nucleotide Sequencing ◽  
Mortality And Morbidity ◽  
Rotavirus A ◽  
Stool Samples ◽  
The Impact

Rotavirus A (RVA) vaccines succeeded in lowering the burden of acute gastroenteritis (AGE) worldwide, especially preventing severe disease and mortality. In 2019, Brazil completed 13 years of RVA vaccine implementation (Rotarix™) within the National Immunization Program (NIP), and as reported elsewhere, the use of Rotarix™ in the country has reduced childhood mortality and morbidity due to AGE. Even though both marketed vaccines are widely distributed, the surveillance of RVA causing AGE and the monitoring of circulating genotypes are important tools to keep tracking the epidemiological scenario and vaccines impact. Thus, our study investigated RVA epidemiological features, viral load and G and P genotypes circulation in children and adults presenting AGE symptoms in eleven states from three out of five regions in Brazil. By using TaqMan®-based one-step RT-qPCR, we investigated a total of 1536 stool samples collected from symptomatic inpatients, emergency department visits and outpatients from January 2018 to December 2019. G and P genotypes of RVA-positive samples were genetically characterized by multiplex RT-PCR or by nearly complete fragment sequencing. We detected RVA in 12% of samples, 10.5% in 2018 and 13.7% in 2019. A marked winter/spring seasonality was observed, especially in Southern Brazil. The most affected age group was children aged >24–60 months, with a positivity rate of 18.8% (p < 0.05). Evaluating shedding, we found a statistically lower RVA viral load in stool samples collected from children aged up to six months compared to the other age groups (p < 0.05). The genotype G3P[8] was the most prevalent during the two years (83.7% in 2018 and 65.5% in 2019), and nucleotide sequencing of some strains demonstrated that they belonged to the emergent equine-like G3P[8] genotype. The dominance of an emergent genotype causing AGE reinforces the need for continuous epidemiological surveillance to assess the impact of mass RVA immunization as well as to monitor the emergence of novel genotypes.

scholarly journals A Simple RP-HPLC Method for the Determination of Omeprazole in Human Serum and Urine: Validation and Application in Pharmacokinetic Study

1970 ◽  
Vol 8 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Kamrun Nahar ◽  
Jafreen Jamal Joti ◽  
Md Ashik Ullah ◽  
Ahasanul Hasan ◽  
Mohammad Abul Kalam Azad ◽  
...  
Keyword(s):  
Human Serum ◽  
Hplc Method ◽  
Stability Study ◽  
Urine Samples ◽  
Dihydrogen Phosphate ◽  
Serum Samples ◽  
Rp Hplc ◽  
Limit Of Quantitation ◽  
Serum And Urine ◽  
Serum And Urine Samples

A Simple RP-HPLC method with UV detection has been validated to determine omeprazole concentrations in human serum and urine samples. The mobile phase consisted of a mixture of potassium dihydrogen phosphate buffer (pH 7.2 ± 0.05; 0.2 M) and acetonitrile (70:30, v/v), pumped at a flow rate of 1.0 ml/min through the C-8 column at room temperature. Peaks were monitored by UV absorbance at 302 nm at a sensitivity of 0.0001. The developed method was selective and linear for omeprazole concentrations ranging between 5 to 1000ng/ml for serum samples and 1 to 100μg/ml for urine samples. The recovery of omeprazole ranged from 95.68 to 99% and 95.54 to 99.8% for the serum and urine samples respectively. The limit of quantitation (LOQ) of omeprazole was 5 ng/ml. The intraday accuracy ranged from 93.54 to 104.38% and 100.55 to 103.48% for the serum and urine respectively. The interday accuracy varied from 97.61 to 113.95% and 97.42 to 109.97% for the serum and urine respectively. For the LOQ, good values of precision (6.03 and 10.13% for intraday and interday, respectively) were also obtained. Acceptable results were obtained during stability study. This method proved to be simple, accurate and precise for pharmacokinetic and bioequivalence studies of omeprazole. Key words: Omeprazole; RP-HPLC; Method validation. DOI: 10.3329/dujps.v8i2.6026 Dhaka Univ. J. Pharm. Sci. 8(2): 123-130, 2009 (December)

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