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 Preanalytical Issues and Cycle Threshold Values in SARS-CoV-2 Real-Time RT-PCR Testing: Should Test Results Include These?

ACS Omega ◽  
2021 ◽  
Author(s):  
Ilka Engelmann ◽  
Enagnon Kazali Alidjinou ◽  
Judith Ogiez ◽  
Quentin Pagneux ◽  
Sana Miloudi ◽  
...  
Keyword(s):  
Real Time ◽  
Test Results ◽  
Threshold Values ◽  
Rt Pcr ◽  
Cycle Threshold

scholarly journals 520. Longitudinal Analysis of SARS-CoV-2 Viruses in Hospitalized Adults

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S325-S326
Author(s):  
Lacy Simons ◽  
Ramon Lorenzo-Redondo ◽  
Hannah Nam ◽  
Scott C Roberts ◽  
Michael G Ison ◽  
...  
Keyword(s):  
Viral Load ◽  
Genome Sequencing ◽  
Viral Genome ◽  
Temporal Dynamics ◽  
Population Level ◽  
Hospital Staff ◽  
Therapeutic Interventions ◽  
Viral Loads ◽  
Qrt Pcr ◽  
Over Time

Abstract Background The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of viral mutations, some of which may have distinct virological and clinical consequences. While whole genome sequencing efforts have worked to map this viral diversity at the population level, little is known about how SARS-CoV-2 may diversify within a host over time. This is particularly important for understanding the emergence of viral resistance to therapeutic interventions and immune pressure. The goal of this study was to assess the change in viral load and viral genome sequence within patients over time and determine if these changes correlate with clinical and/or demographic parameters. Methods Hospitalized patients admitted to Northwestern Memorial Hospital with a positive SARS-CoV-2 test were enrolled in a longitudinal study for the serial collection of nasopharyngeal specimens. Swabs were administered to patients by hospital staff every 4 ± 1 days for up to 32 days or until the patients were discharged. RNA was extracted from each specimen and viral loads were calculated by quantitative reverse transcriptase PCR (qRT-PCR). Specimens with qRT-PCR cycle threshold values less than or equal to 30 were subject to whole viral genome sequencing by reverse transcription, multiplex PCR, and deep sequencing. Variant populations sizes were estimated and subject to phylogenetic analysis relative to publicly available SARS-CoV-2 sequences. Sequence and viral load data were subsequently correlated to available demographic and clinical data. Results 60 patients were enrolled from March 26th to June 20th, 2020. We observed an overall decrease in nasopharyngeal viral load over time across all patients. However, the temporal dynamics of viral load differed on a patient-by-patient basis. Several mutations were also observed to have emerged within patients over time. Distribution of SARS-CoV-2 viral loads in serially collected nasopharyngeal swabs in hospitalized adults as determined by qRT-PCR. Samples were collected every 4 ± 1 days (T#1–8) and viral load is displayed by log(copy number). Conclusion These data indicate that SARS-CoV-2 viral loads in the nasopharynx decrease over time and that the virus can accumulate mutations during replication within individual patients. Future studies will examine if some of these mutations may provide fitness advantages in the presence of therapeutic and/or immune selective pressures. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)

scholarly journals Differential Kinetics of Cycle Threshold Values during Admission by Symptoms among Patients with Mild COVID-19: A Prospective Cohort Study

2021 ◽  
Vol 18 (15) ◽  
pp. 8181
Author(s):  
Teppei Sakano ◽  
Mitsuyoshi Urashima ◽  
Hiroyuki Takao ◽  
Kohei Takeshita ◽  
Hiroe Kobashi ◽  
...  
Keyword(s):  
Cohort Study ◽  
Viral Load ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Polymerase Chain Reaction Test ◽  
Cycle Threshold ◽  
Viral Loads ◽  
Asymptomatic Patients ◽  
Asymptomatic Individuals ◽  
Chain Reaction Test

In the coronavirus disease 2019 (COVID-19) pandemic, more than half of the cases of transmission may occur via asymptomatic individuals, which makes it difficult to contain. However, whether viral load in the throat during admission is different between asymptomatic and symptomatic patients is not well known. By conducting a prospective cohort study of patients with asymptomatic or mild COVID-19, cycle threshold (Ct) values of the polymerase chain reaction test for COVID-19 were examined every other day during admission. The Ct values during admission increased more steadily in symptomatic patients and febrile patients than in asymptomatic patients, with significance (p = 0.01 and p = 0.004, respectively), although the Ct values as a whole were not significantly different between the two groups. Moreover, the Ct values as a whole were higher in patients with dysosmia/dysgeusia than in those without it (p = 0.02), whereas they were lower in patients with a headache than those without (p = 0.01). Patients who were IgG-positive at discharge maintained higher Ct values, e.g., more than 35, during admission than those with IgG-negative (p = 0.03). Assuming that viral load and Ct values are negatively associated, the viral loads as a whole and their changes by time may be different by symptoms and immune reaction, i.e., IgG-positive at discharge.

scholarly journals Assessment of Commercial DNA Cleanup Kits for Elimination of Real-Time PCR Inhibitors in the Detection of Cyclospora cayetanensis in Cilantro

2020 ◽  
Vol 83 (11) ◽  
pp. 1863-1870
Author(s):  
ANGELA ASSURIAN ◽  
HELEN MURPHY ◽  
ALICIA SHIPLEY ◽  
HEDIYE NESE CINAR ◽  
ALEXANDRE DA SILVA ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
False Negative ◽  
Threshold Values ◽  
Cyclospora Cayetanensis ◽  
Cycle Threshold ◽  
Negative Results ◽  
False Negative Results ◽  
Pcr Inhibitor ◽  
Zymo Research

ABSTRACT Inhibited reactions have occasionally been observed when cilantro samples were processed for the detection of Cyclospora cayetanensis using quantitative real-time PCR (qPCR). Partial or total inhibition of PCR reactions, including qPCR, can occur, leading to decreased sensitivity or false-negative results. If inhibition occurs, this implies the need for additional purification or cleanup treatments of the extracted DNA to remove inhibitors prior to molecular detection. Our objective was to evaluate the performance of five commercial DNA cleanup kits (QIAquick purification kit from Qiagen [kit 1], OneStep PCR inhibitor removal by Zymo Research [kit 2], NucleoSpin genomic DNA cleanup XS from Macherey-Nagel [kit 3], DNA IQ system by Promega [kit 4], and DNeasy PowerPlant pro kit from Qiagen [5]) to minimize qPCR inhibition using the U.S. Food and Drug Administration–validated Bacteriological Analytical Manual (BAM) Chapter 19b method for detection of C. cayetanensis in cilantro samples containing soil. Each of the five commercial DNA cleanup kits evaluated was able to reduce the qPCR internal amplification control cycle threshold values to those considered to be normal for noninhibited samples, allowing unambiguous interpretation of results in cilantro samples seeded at both a high oocyst level (200 oocysts) and a low oocyst level (10 oocysts). Of the five kits compared, kits 1, 2, and 3 did not show significant differences in the detection of C. cayetanensis, while significantly higher cycle threshold values, indicating lower recovery of the target DNA, were observed from kits 4 and/or 5 in samples seeded with 200 and 10 oocysts (P < 0.05). This comparative study provides recommendations on the use of commercial cleanup kits which could be implemented when inhibition is observed in the detection of C. cayetanensis in cilantro samples using the BAM Chapter 19b method. HIGHLIGHTS

scholarly journals SARS-CoV-2 Viral RNA Load Dynamics in the Nasopharynx of Infected Children

2020 ◽  
Author(s):  
Kai-qian Kam ◽  
Koh Cheng Thoon ◽  
Matthias Maiwald ◽  
Chia Yin Chong ◽  
Han Yang Soong ◽  
...  
Keyword(s):  
Viral Load ◽  
Early Stage ◽  
Transmission Potential ◽  
Cycle Threshold ◽  
Viral Loads ◽  
Viral Shedding ◽  
Asymptomatic Children ◽  
Peak Viral Load ◽  
Epidemiological Risk ◽  
Mean Cycle

It is important to understand the temporal trend of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load to estimate the transmission potential of children in schools and communities. We determined differences in SARS-CoV-2 viral load dynamics between nasopharyngeal samples of infected asymptomatic and symptomatic children. The daily cycle threshold values of SARS-CoV-2 in the nasopharynx of a cohort of infected children were collected for analysis. Among 17 infected children, 10 (58.8%) were symptomatic. Symptomatic children, when compared to asymptomatic children, had higher viral load (mean cycle threshold on day 7 of illness 28.6 versus 36.7, p = 0.02). Peak SARS-CoV-2 viral loads occured around days 2-3 of illness/days of diagnosis in infected children. After adjusting for the estimated date of infection, the higher SARS-CoV-2 viral loads in symptomatic children remained. We postulate that symptomatic SARS-CoV-2-infected children may have higher transmissibility than asymptomatic children. As peak viral load in infected children occurred in the early stage of illness, viral shedding and transmission in the pre-symptomatic phase probable. Our study highlights the importance of screening for SARS-CoV-2 in children with epidemiological risk factors, even when they are asymptomatic in order to improve containment of the virus in the community, including educational settings.

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.

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