scholarly journals Association of cycle threshold values of CBNAAT with severity and outcome in COVID-19

2021 ◽  
Author(s):  
Kranti Garg ◽  
Karan Sharma ◽  
Aditi Gupta ◽  
Vishal Chopra
Keyword(s):  
Viral Load ◽  
Virus Disease ◽  
Nucleic Acid Amplification ◽  
Clinical Parameters ◽  
Surrogate Markers ◽  
Threshold Values ◽  
Cycle Threshold ◽  
E Gene ◽  
Disease Outcomes

Determination of viral load through cycle threshold (Ct) values may act as a predictor of severity and outcomes in patients with corona virus disease 2019 (COVID-19). However, variable literature is available regarding this relationship. Our study attempted to explore this association and the effect of various socio-demographic and clinical parameters on severity and outcome of COVID-19.  Retrospective analysis of records of 731 patients whose nasopharyngeal/ oropharyngeal swabs were subjected to cartridge based nucleic acid amplification (CBNAAT) on Cepheid Xpert Xpress SARS-Cov-2 was done. Cycle threshold (Ct) values of N2 and E genes were studied in relation to severity and outcome of COVID-19. The viral load as determined by Ct values was classified as high (<25), medium (25.1-32) and low (>32). Association of socio-demographic and clinical parameters with respect to severity and outcome was also studied. Severity and mortality were significantly more in elder individuals, those belonging to the rural background, those with symptoms >7 days in duration before presentation and those with increasing number of co-morbidities (Severity: p<0.001, mortality: p <0.001, 0.005, 0.006 and <0.001 respectively). The Ct values of gene N2 and E inversely correlated with severity and mortality from the disease (N2 gene: p=0.001 for both severity and mortality, E gene: severity: p<0.001, mortality: p=0.016 respectively). The severity of the illness and chances of mortality were significantly lesser when the CT value of N2 gene was >32, in comparison when it was upto 25, and when between 25.1 and 32 (severity: p=0.032 and 0.003 respectively, mortality: p=0.018 and <0.001 respectively). Almost similar trends were seen with respect to E gene (severity: p<0.001 and 0.067 respectively, mortality p=0.175 and 0.005 respectively). Viral load as determined by Ct values of N2 and E genes can act as surrogate markers for prediction of severity and disease outcomes in COVID-19.

scholarly journals KI and WU Polyomavirus in Respiratory Samples of SARS-CoV-2 Infected Patients

2021 ◽  
Vol 9 (6) ◽  
pp. 1259
Author(s):  
Carla Prezioso ◽  
Ugo Moens ◽  
Giuseppe Oliveto ◽  
Gabriele Brazzini ◽  
Francesca Piacentini ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Healthcare Workers ◽  
Respiratory Pathogens ◽  
Threshold Values ◽  
Cycle Threshold ◽  
Viral Interference ◽  
Disease Outcomes ◽  
Global Pandemic ◽  
Wu Polyomavirus ◽  
Washington University

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether co-infections with respiratory polyomaviruses, such as Karolinska Institutet polyomavirus (KIPyV) and Washington University polyomavirus (WUPyV) occur in SARS-CoV-2 infected patients. Oropharyngeal swabs from 150 individuals, 112 symptomatic COVID-19 patients and 38 healthcare workers not infected by SARS-CoV-2, were collected from March 2020 through May 2020 and tested for KIPyV and WUPyV DNA presence. Of the 112 SARS-CoV-2 positive patients, 27 (24.1%) were co-infected with KIPyV, 5 (4.5%) were positive for WUPyV, and 3 (2.7%) were infected simultaneously by KIPyV and WUPyV. Neither KIPyV nor WUPyV DNA was detected in samples of healthcare workers. Significant correlations were found in patients co-infected with SARS-CoV-2 and KIPyV (p < 0.05) and between SARS-CoV-2 cycle threshold values and KIPyV, WUPyV and KIPyV and WUPyV concurrently detected (p < 0.05). These results suggest that KIPyV and WUPyV may behave as opportunistic respiratory pathogens. Additional investigations are needed to understand the epidemiology and the prevalence of respiratory polyomavirus in COVID-19 patients and whether KIPyV and WUPyV could potentially drive viral interference or influence disease outcomes by upregulating SARS-CoV-2 replicative potential.

scholarly journals Comparative performance and cycle threshold values of 10 nucleic acid amplification tests for SARS-CoV-2 on clinical samples

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252757
Author(s):  
Miyuki Mizoguchi ◽  
Sohei Harada ◽  
Koh Okamoto ◽  
Yoshimi Higurashi ◽  
Mahoko Ikeda ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Diagnostic Performance ◽  
Nucleic Acid Amplification ◽  
Clinical Samples ◽  
Nucleic Acid Amplification Tests ◽  
Cycle Threshold ◽  
E Gene ◽  
Viral Copy Number ◽  
Gene Test ◽  
Positive Results

Background A number of nucleic acid amplification tests (NAATs) for SARS-CoV-2 with different reagents have been approved for clinical use in Japan. These include research kits approved under emergency use authorization through simplified process to stabilize the supply of the reagents. Although these research kits have been increasingly used in clinical practice, limited data is available for the diagnostic performance in clinical settings. Methods We compared sensitivity, specificity, and cycle threshold (Ct) values obtained by NAATs using 10 kits approved in Japan including eight kits those receiving emergency use authorization using 69 frozen-stored clinical samples including 23 positive samples with various Ct values and 46 negative samples. Results Viral copy number of the frozen-stored samples determined with LightMix E-gene test ranged from 0.6 to 84521.1 copies/μL. While no false-positive results were obtained by any of these tests (specificity: 100% [95% CI, 88.9%-100%]), sensitivity of the nine tests ranged from 68.2% [95% CI, 45.1%-86.1%] to 95.5% [95% CI, 77.2%-99.9%] using LightMix E-gene test as the gold standard. All tests showed positive results for all samples with ≥100 copies/μL. Significant difference of Ct values even among tests amplifying the same genetic region (N1-CDC, N2) was also observed. Conclusion Difference in the diagnostic performance was observed among NAATs approved in Japan. Regarding diagnostic kits for emerging infectious diseases, a system is needed to ensure both rapidity of reagent supply and accuracy of diagnosis. Ct values, which are sometimes regarded as a marker of infectivity, are not interchangeable when obtained by different assays.

scholarly journals The 501Y.V2 SARS-CoV-2 variant has an intermediate viral load between the 501Y.V1 and the historical variants in nasopharyngeal samples from newly diagnosed COVID-19 patients

2021 ◽  
Author(s):  
Elisa Teyssou ◽  
Cathia Soulie ◽  
Benoit Visseaux ◽  
Sidonie Lambert-Niclot ◽  
Valentine Ferre ◽  
...  
Keyword(s):  
Viral Load ◽  
Newly Diagnosed ◽  
Threshold Values ◽  
Rt Pcr ◽  
Cycle Threshold ◽  
The World

The 501Y.V2 and the 501Y.V1 SARS-CoV-2 variants emerged and spread rapidly into the world. We analysed the RT-PCR cycle threshold values of 643 nasopharyngeal samples of COVID-19 patients at diagnosis and found that the 501Y.V2 variant presented an intermediate viral load between the 501Y.V1 and the historical variants.

scholarly journals Vitamin A Supplementation Was Associated with Reduced Mortality in Patients with Ebola Virus Disease during the West African Outbreak

2019 ◽  
Vol 149 (10) ◽  
pp. 1757-1765 ◽  
Author(s):  
Adam R Aluisio ◽  
Shiromi M Perera ◽  
Derrick Yam ◽  
Stephanie Garbern ◽  
Jillian L Peters ◽  
...  
Keyword(s):  
Vitamin A ◽  
Ebola Virus ◽  
Propensity Scores ◽  
Resource Constraints ◽  
Clinical Symptoms ◽  
Virus Disease ◽  
Ebola Virus Disease ◽  
Threshold Values ◽  
Vitamin A Supplementation ◽  
Cycle Threshold

ABSTRACT Background Micronutrient supplementation is recommended in Ebola virus disease (EVD); however, there are limited data on therapeutic impacts of specific micronutrients. Objective To evaluate the association between vitamin A supplementation and mortality in EVD. Methods This retrospective cohort included patients with EVD admitted to 5 International Medical Corps Ebola Treatment Units (ETUs) in 2 countries during 2014–2015. Protocolized treatments with micronutrients were used at all ETUs: however, because of resource constraints, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola viral loads (cycle threshold values) were collected. The outcome of interest was mortality between cases treated with 200,000 IU of vitamin A on care days 1 and/or 2, and those not. Propensity scores based on the first 48 h of care were derived using covariates of age, ETU duration, malaria status, cycle threshold values, and clinical symptoms. Patients were matched 1:1 using nearest neighbors with replacement. Mortality between cases treated and not treated with vitamin A was compared using generalized estimating equations to calculate RR with associated 95% CI. Results There were 424 cases analyzed, of which 330 (77.8%) were treated with vitamin A. The mean age was 30.5 y and 40.3% were men. The most common symptoms were diarrhea (85.6%), anorexia (80.7%), and abdominal pain (76.9%). Mortality proportions among cases treated and not treated with vitamin A were 55.0% and 71.9%, respectively. In the propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77, 95% CI: 0.59, 0.99; P = 0.041). In a subgroup analysis of patients treated with multivitamins already containing vitamin A, additional vitamin A supplementation did not impact mortality. Conclusion Early vitamin A supplementation was associated with reduced mortality in patients with EVD, and should be further studied and considered for use in future epidemics.

scholarly journals Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmissibility

2021 ◽  
Author(s):  
Yun Lin ◽  
Bingyi Yang ◽  
Sarah Cobey ◽  
Eric Lau ◽  
Dillon Adam ◽  
...  
Keyword(s):  
Viral Load ◽  
Real Time ◽  
Temporal Distribution ◽  
Time Estimation ◽  
Population Level ◽  
Reproductive Number ◽  
Threshold Values ◽  
Illness Onset ◽  
Cycle Threshold ◽  
Viral Loads

Abstract Many locations around the world have used real-time estimates of the time-varying effective reproductive number (\({R}_{t}\)) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of \({R}_{t}\) are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the incubation period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by cycle threshold values) and estimates of \({R}_{t}\) based on case counts. We demonstrate that cycle threshold values could be used to improve real-time \({R}_{t}\) estimation, enabling more timely tracking of epidemic dynamics.

scholarly journals SARS-CoV-2 Viral Load, IFNλ Polymorphisms and the Course of COVID-19: An Observational Study

2020 ◽  
Vol 9 (10) ◽  
pp. 3315
Author(s):  
Emanuele Amodio ◽  
Rosaria Maria Pipitone ◽  
Stefania Grimaudo ◽  
Palmira Immordino ◽  
Carmelo Massimo Maida ◽  
...  
Keyword(s):  
Viral Load ◽  
Observational Study ◽  
Lower Risk ◽  
Nucleotide Polymorphisms ◽  
Threshold Values ◽  
Single Nucleotide ◽  
Cycle Threshold ◽  
Viral Loads ◽  
The Relationship ◽  
Multiorgan Disease

The course of SARS-CoV-2 infection ranges from asymptomatic to a multiorgan disease. In this observational study, we investigated SARS-CoV-2 infected subjects with defined outcomes, evaluating the relationship between viral load and single nucleotide polymorphisms of genes codifying for IFNλs (interferon). The study enrolled 381 patients with laboratory-confirmed SARS-CoV-2 infection. For each patient, a standardized form was filled including sociodemographic variables and clinical outcomes. The host’s gene polymorphisms (IFNL3 rs1297860 C/T and INFL4 rs368234815 TT/ΔG) and RtReal-Time PCR cycle threshold (PCR Ct) value on SARS-CoV-2 were assessed on nasal, pharyngeal or nasopharyngeal swabs. Higher viral loads were found in patients aged > 74 years and homozygous mutant polymorphisms DG in IFNL4 (adj-OR = 1.16, 95% CI = 1.01–1.34 and adj-OR = 1.24, 95% CI = 1.09–1.40, respectively). After adjusting for age and sex, a statistically significantly lower risk of hospitalization was observed in subjects with higher RtReal-Time PCR cycle threshold values (adj-OR = 0.95, 95% CI = 0.91, 0.99; p = 0.028). Our data support the correlation between SARS-CoV-2 load and disease severity, and suggest that IFNλ polymorphisms could affect the ability of the host to modulate viral infection without a clear impact on the outcome of COVID-19.

scholarly journals Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

2020 ◽  
Vol 25 (32) ◽  
Author(s):  
Anika Singanayagam ◽  
Monika Patel ◽  
Andre Charlett ◽  
Jamie Lopez Bernal ◽  
Vanessa Saliba ◽  
...  
Keyword(s):  
Viral Load ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Upper Respiratory Tract ◽  
Threshold Values ◽  
Rt Pcr ◽  
Cycle Threshold ◽  
Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

scholarly journals Modelling RT-qPCR cycle-threshold using digital PCR data for implementing SARS-CoV-2 viral load studies

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260884
Author(s):  
Fabio Gentilini ◽  
Maria Elena Turba ◽  
Francesca Taddei ◽  
Tommaso Gritti ◽  
Michela Fantini ◽  
...  
Keyword(s):  
Viral Load ◽  
Regression Model ◽  
Case Fatality ◽  
High Specificity ◽  
Digital Pcr ◽  
Public Health Authority ◽  
Load Factor ◽  
Threshold Values ◽  
Cycle Threshold ◽  
Low Sensitivity

Objectives To exploit the features of digital PCR for implementing SARS-CoV-2 observational studies by reliably including the viral load factor expressed as copies/μL. Methods A small cohort of 51 Covid-19 positive samples was assessed by both RT-qPCR and digital PCR assays. A linear regression model was built using a training subset, and its accuracy was assessed in the remaining evaluation subset. The model was then used to convert the stored cycle threshold values of a large dataset of 6208 diagnostic samples into copies/μL of SARS-CoV-2. The calculated viral load was used for a single cohort retrospective study. Finally, the cohort was randomly divided into a training set (n = 3095) and an evaluation set (n = 3113) to establish a logistic regression model for predicting case-fatality and to assess its accuracy. Results The model for converting the Ct values into copies/μL was suitably accurate. The calculated viral load over time in the cohort of Covid-19 positive samples showed very low viral loads during the summer inter-epidemic waves in Italy. The calculated viral load along with gender and age allowed building a predictive model of case-fatality probability which showed high specificity (99.0%) and low sensitivity (21.7%) at the optimal threshold which varied by modifying the threshold (i.e. 75% sensitivity and 83.7% specificity). Alternative models including categorised cVL or raw cycle thresholds obtained by the same diagnostic method also gave the same performance. Conclusion The modelling of the cycle threshold values using digital PCR had the potential of fostering studies addressing issues regarding Sars-CoV-2; furthermore, it may allow setting up predictive tools capable of early identifying those patients at high risk of case-fatality already at diagnosis, irrespective of the diagnostic RT-qPCR platform in use. Depending upon the epidemiological situation, public health authority policies/aims, the resources available and the thresholds used, adequate sensitivity could be achieved with acceptable low specificity.

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