scholarly journals Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
A Sarah Walker ◽  
Emma Pritchard ◽  
Thomas House ◽  
Julie V Robotham ◽  
Paul J Birrell ◽  
...  
Keyword(s):  
Viral Load ◽  
Single Gene ◽  
Population Level ◽  
National Institutes Of Health ◽  
Rt Pcr ◽  
Department Of Health ◽  
Health And Social Care ◽  
Antibody Tests ◽  
Nose And Throat ◽  
Over Time

Background: Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load).Methods: We included all positive nose and throat swabs 26-April-2020 to 13-March-2021 from the UK's national COVID-19 Infection Survey, tested by RT-PCR for the N, S and ORF1ab genes. We investigated predictors of median Ct value using quantile regression.Results: Of 3,312,159 nose and throat swabs, 27,902(0.83%) were RT-PCR-positive, 10,317(37%), 11,012(40%) and 6,550(23%) for 3, 2 or 1 of the N, S and ORF1ab genes respectively, with median Ct=29.2 (~215 copies/ml; IQR Ct=21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity and age. Single-gene positives almost invariably had Ct>30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity.Of 6,189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4,808(78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody-negative.Conclusions: Marked variation in community SARS-CoV-2 Ct values suggest that they could be a useful epidemiological early-warning indicator.Funding: Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.

scholarly journals Viral load in community SARS-CoV-2 cases varies widely and temporally

2020 ◽  
Author(s):  
A. Sarah Walker ◽  
Emma Pritchard ◽  
Thomas House ◽  
Julie V Robotham ◽  
Paul J Birrell ◽  
...  
Keyword(s):  
Viral Load ◽  
Early Warning ◽  
Single Gene ◽  
Supporting Evidence ◽  
Cycle Threshold ◽  
Early Warning Indicator ◽  
Test Characteristics ◽  
Independent Effects ◽  
Nose And Throat ◽  
Over Time

ABSTRACTBackgroundInformation on COVID-19 in representative community surveillance is limited, particularly regarding cycle threshold (Ct) values (a proxy for SARS-CoV-2 viral load) and symptoms.MethodsWe included all positive nose and throat swabs between 26 April-11 October 2020 from the UK’s national COVID-19 Infection Survey, tested by RT-PCR for the N, S and ORF1ab genes. We investigated predictors of median Ct value using quantile regression.Results1892(0.22%) of 843,851 results were positive, 1362(72%), 185(10%) and 345(18%) for 3, 2 or 1 genes respectively. Ct for different genes were strongly correlated (rho=0.99) with overall median Ct 26.2 (IQR 19.7-31.1; range 10.3-37.6), corresponding to ∼2,500 dC/ml (IQR 80-240,000). Ct values were independently lower in those reporting symptoms, with more genes detected, and in first (vs. subsequent) positives per-participant, with no evidence of independent effects of sex, ethnicity, age, deprivation or other test characteristics (p>0.20). Whilst single-gene positives without reported symptoms almost invariably had Ct>30, triple-gene positives without reported symptoms had widely varying Ct. Incorporating pre-test probability and Ct values, 1547(82%) and 112(6%) positives had “higher” or “lower” supporting evidence for genuine infection. Ct values, symptomatic percentages and supporting evidence changed over time. With lower positivity in the summer, there were proportionally more “lower” evidence positives, and “higher” evidence positives had higher Ct values (p<0.0001), suggesting lower viral burden. Declines in mean/median Ct values were apparent throughout August and preceded increases in positivity rates.ConclusionsCommunity SARS-CoV-2 infections show marked variation in viral load. Ct values could be a useful epidemiological early-warning indicator.SUMMARYCycle threshold (Ct) values in community SARS-CoV-2 infections from national surveillance vary markedly, including over time and by symptoms (1892 (0.22%) positive nose and throat swabs, 843,851 tested). Ct values could be a useful epidemiological early warning indicator.

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 Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients

2020 ◽  
Vol 71 (15) ◽  
pp. 793-798 ◽  
Author(s):  
Fengting Yu ◽  
Liting Yan ◽  
Nan Wang ◽  
Siyuan Yang ◽  
Linghang Wang ◽  
...  
Keyword(s):  
Viral Load ◽  
Target Genes ◽  
Single Gene ◽  
Clinical Staging ◽  
N Gene ◽  
Quantitative Detection ◽  
Imaging Data ◽  
Rt Pcr ◽  
Viral Loads ◽  
Nasal Swabs

Abstract Background Coronavirus disease 2019 (COVID-19) has become a public health emergency. The widely used reverse transcription–polymerase chain reaction (RT-PCR) method has limitations for clinical diagnosis and treatment. Methods A total of 323 samples from 76 COVID-19–confirmed patients were analyzed by droplet digital PCR (ddPCR) and RT-PCR based 2 target genes (ORF1ab and N). Nasal swabs, throat swabs, sputum, blood, and urine were collected. Clinical and imaging data were obtained for clinical staging. Results In 95 samples that tested positive by both methods, the cycle threshold (Ct) of RT-PCR was highly correlated with the copy number of ddPCR (ORF1ab gene, R2 = 0.83; N gene, R2 = 0.87). Four (4/161) negative and 41 (41/67) single-gene positive samples tested by RT-PCR were positive according to ddPCR with viral loads ranging from 11.1 to 123.2 copies/test. The viral load of respiratory samples was then compared and the average viral load in sputum (17 429 ± 6920 copies/test) was found to be significantly higher than in throat swabs (2552 ± 1965 copies/test, P &lt; .001) and nasal swabs (651 ± 501 copies/test, P &lt; .001). Furthermore, the viral loads in the early and progressive stages were significantly higher than that in the recovery stage (46 800 ± 17 272 vs 1252 ± 1027, P &lt; .001) analyzed by sputum samples. Conclusions Quantitative monitoring of viral load in lower respiratory tract samples helps to evaluate disease progression, especially in cases of low viral load.

scholarly journals Viral load of SARS-CoV-2 across patients and compared to other respiratory viruses

2020 ◽  
Author(s):  
Damien Jacot ◽  
Gilbert Greub ◽  
Katia Jaton ◽  
Onya Opota
Keyword(s):  
Viral Load ◽  
Respiratory Viruses ◽  
Rt Pcr ◽  
Clinical Prognosis ◽  
Clinical Specimens ◽  
Viral Loads ◽  
Over Time

RT-PCR to detect SARS-CoV-2 RNA in clinical specimens was key to manage the COVID-19 pandemic. We monitored SARS-CoV-2 viral loads over time and across different patient populations. We analyzed RT-PCR results according to samples types, gender, age, and health units and compared SARS-CoV-2 viral load to other respiratory viruses, representing a total of 28,373 RT-PCR results including 22,323 SARS-CoV-2 RT-PCR. The importance of viral load to predict contagiousness and clinical prognosis is discussed.

scholarly journals Variation across population subgroups of COVID-19 antibody testing performance

2020 ◽  
Author(s):  
Halley L Brantley ◽  
Richard M Yoo ◽  
Glen I Jones ◽  
Marel A Stock ◽  
Peter J Park ◽  
...  
Keyword(s):  
Test Performance ◽  
Rt Pcr ◽  
Antibody Testing ◽  
Serological Tests ◽  
Demographic Groups ◽  
Significant Difference ◽  
Testing Performance ◽  
Large Populations ◽  
Antibody Tests ◽  
Over Time

Understanding variations in the performance of serological tests for SARS-CoV-2 across varying demographics is relevant to clinical interpretations and public policy derived from their results. Appropriate use of serological assays to detect anti-SARS-CoV-2 antibodies requires estimation of their accuracy over large populations and an understanding of the variance in performance over time and across demographic groups. In this manuscript we focus on anti-SARS-CoV-2 IgG, IgA, and IgM antibody tests approved under emergency use authorizations and determine the recall of the serological tests compared to RT-PCR tests by Logical Observation Identifiers Names and Codes (LOINCs). Variability in test performance was further examined over time and by demographics. The recall of the most common IgG assay (LOINC 94563-4) was 91.2% (95% CI: 90.5%, 91.9%). IgA (LOINC 94562-6) and IgM (94564-2) assays performed significantly worse than IgG assays with estimated recall rates of 20.6% and 27.3%, respectively. A statistically significant difference in recall (p = 0.019) was observed across sex with a higher recall in males than females, 92.1% and 90.4%, respectively. Recall also differed significantly by age group, with higher recall in those over 45 compared to those under 45, 92.9% and 88.0%, respectively (p < 0.001). While race was unavailable for the majority of the individuals, a significant difference was observed between recall in White individuals and Black individuals (p = 0.007) and White individuals and Hispanic individuals (p=0.001). The estimates of recall were 89.3%, 95.9%, and 94.2% for White, Black, and Hispanic individuals respectively.

scholarly journals Clinical characteristics and viral load dynamics of COVID-19 in a mildly or moderately symptomatic outpatient sample

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258970
Author(s):  
Amanda Caplan ◽  
Kelly W. Bates ◽  
Carla Brioni ◽  
Aileen Santos ◽  
Linda M. Sabatini ◽  
...  
Keyword(s):  
Viral Load ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Symptom Duration ◽  
Test Results ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Antibody Tests ◽  
Pcr Test

Background Studies of outpatients with mild or moderate COVID-19 are uncommon. We studied: 1) association of symptoms with reverse transcriptase polymerase chain reaction (RT-PCR) test results; and 2) association of initial RT-PCR cycle threshold (Ct) in relation to duration of RT-PCR positivity in outpatients with mild or moderate COVID-19. Methods This was a cohort study of outpatients with confirmed COVID-19 and at least one symptom. Participants had repeat nasopharyngeal swabs and symptom checklists every 3–5 days until two consecutive RT-PCR tests were negative. RT-PCR tests were used to assess viral load. Antibody tests for COVID-19 were performed at 2 weeks, 4 weeks, and 8 weeks after symptom onset. Results Twenty-five patients (nine females) were enrolled, ranging in age from 19–58 (median age 28 years). All patients reported at least one symptom, with a median of six symptoms per patient. Symptoms persisted for 6–67 days (median duration 18 days). In all 25 patients, blood samples collected a median of 13 days after symptom onset were positive for SARS-CoV-2 antibodies in 15 (60%). After a median of 28 days following symptom onset, 23/23 patients with available samples tested positive for antibodies. The longest duration of positive RT-PCR test was 49 days from first positive PCR test (Mean = 27.4, SD = 12.5, Median = 24). Initial Ct was significantly associated with longer duration (β = -1.3, SE = 0.3, p<0.01 per 1 cycle higher) of RT-PCR positivity. Conclusions In mildly or moderately ill COVID-19 outpatients, RT-PCT tests remained positive for as long as 49 days and test positivity and symptom duration correlated with initial viral load.

scholarly journals Increased infections, but not viral burden, with a new SARS-CoV-2 variant

2021 ◽  
Author(s):  
A. Sarah Walker ◽  
Karina-Doris Vihta ◽  
Owen Gethings ◽  
Emma Pritchard ◽  
Joel Jones ◽  
...  
Keyword(s):  
Growth Rates ◽  
Population Level ◽  
Older Individuals ◽  
Infection Rates ◽  
Rt Pcr ◽  
Gene Target ◽  
New Variant ◽  
Nationally Representative ◽  
The Uk ◽  
Nose And Throat

ABSTRACTBackgroundA new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited.MethodsNose and throat swabs from 28-September-2020 to 2-January-2021 in the UK’s nationally representative surveillance study were tested by RT-PCR for three genes (N, S and ORF1ab). Those positive only on ORF1ab+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives.Results15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)).ConclusionsDirect population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.

scholarly journals Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1091
Author(s):  
Ali A. Rabaan ◽  
Raghavendra Tirupathi ◽  
Anupam A Sule ◽  
Jehad Aldali ◽  
Abbas Al Mutair ◽  
...  
Keyword(s):  
Viral Load ◽  
Real Time ◽  
Disease Severity ◽  
False Negative ◽  
Influential Factors ◽  
Confirmatory Test ◽  
Acid Extraction ◽  
Rt Pcr ◽  
Viral Kinetics ◽  
Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

scholarly journals Recomposing persons: Scavenging and storytelling in a birth cohort archive

2021 ◽  
pp. 095269512199539
Author(s):  
Penny Tinkler ◽  
Resto Cruz ◽  
Laura Fenton
Keyword(s):  
Life Course ◽  
Cohort Studies ◽  
Birth Cohort ◽  
Quantitative Data ◽  
Population Level ◽  
Relational Embeddedness ◽  
The Life Course ◽  
Over Time

Birth cohort studies can be used not only to generate population-level quantitative data, but also to recompose persons. The crux is how we understand data and persons. Recomposition entails scavenging for various (including unrecognised) data. It foregrounds the perspective and subjectivity of survey participants, but without forgetting the partiality and incompleteness of the accounts that it may generate. Although interested in the singularity of individuals, it attends to the historical and relational embeddedness of personhood. It examines the multiple and complex temporalities that suffuse people’s lives, hence departing from linear notions of the life course. It implies involvement, as well as reflexivity, on the part of researchers. It embraces the heterogeneity and transformations over time of scientific archives and the interpretive possibilities, as well as incompleteness, of birth cohort studies data. Interested in the unfolding of lives over time, it also shines light on meaningful biographical moments.

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