scholarly journals Inferring SARS-CoV-2 variant within-host kinetics

2021 ◽  
Author(s):  
Baptiste Elie ◽  
Emmanuel Lecorche ◽  
Mircea T. Sofonea ◽  
Sabine Trombert ◽  
Vincent Foulogne ◽  
...  
Keyword(s):  
Viral Load ◽  
General Population ◽  
Host Population ◽  
Screening Tests ◽  
Infectious Period ◽  
Wild Type ◽  
Cycle Threshold ◽  
Transmission Data ◽  
Peak Viral Load ◽  
Period Duration

SARS-CoV-2 variants are causing epidemic rebounds in many countries. By analyzing longitudinal cycle threshold (Ct) values from screening tests in the general population and hospitals, we find that infections caused by variant lineages have higher peak viral load than wild type lineages and, for the B.1.1.7 lineage, have a longer infectious period duration. Linking within-host kinetics to transmission data suggests that infections caused by variants have higher transmission potentials and that their epidemiological fitness may depend on the demography of the host population.

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 Transmissibility of COVID-19 among Vaccinated Individuals: A Rapid Literature Review

2021 ◽  
Author(s):  
Oluwaseun Egunsola ◽  
Liza Mastikhina ◽  
Laura Dowsett ◽  
Brenlea Farkas ◽  
Mark Hofmeister ◽  
...  
Keyword(s):  
Viral Load ◽  
General Population ◽  
Observational Studies ◽  
Animal Studies ◽  
Asymptomatic Infection ◽  
Controlled Trials ◽  
Lower Viral Load ◽  
Full Dose ◽  
Cycle Threshold ◽  
Household Transmission

Objectives: This is an update of a previous report that examined literature published up to March 11th, 2021. Sixteen additional studies have been included in this update. The objective of this report is to identify comparative observational studies and randomized controlled trials (RCTs) evaluating the efficacy and effectiveness of COVID-19 vaccination in reducing forward transmission from vaccinated people, and studies examining the biological plausibility of vaccination-induced transmission reduction. Method: A search of databases, MEDLINE, Embase, L-OVE and the Cochrane Central Register of Controlled Trials was conducted to identify RCTs or comparative observational studies evaluating the efficacy and effectiveness of COVID-19 vaccination in the prevention of transmission, asymptomatic infections and transmissibility of COVID-19 among vaccinated persons. An additional search of grey literature was conducted. This search is current to May 4th, 2021. Results: In this update, 16 additional studies, including 9 human and 7 animal studies, were included. Therefore, this review examines a total of 33 included studies: 21 human studies and 12 preclinical animal studies. Evidence from two large household surveillance studies from the UK suggests that a single or full dose of AstraZeneca (AZ) and Pfizer-BioNtech (PfBnT) vaccines may prevent household transmission of COVID-19 after 14 days of vaccination by up to 54%. The AZ vaccine trials in the general population suggest that an initial low dose followed by a standard dose may provide up to 59% protection against asymptomatic or unknown infection, although efficacy against these outcomes was not demonstrated following two standard doses. PfBnT vaccine observational studies in the general population suggest up to 90% effectiveness against asymptomatic infection after seven or more days of full dose vaccination. Up to 75% effectiveness against asymptomatic infection was reported after full-dose in healthcare workers. Across RCTs examining asymptomatic infection in the general population, one dose of Moderna was shown to provide an efficacy of 61.4% against asymptomatic infection 21 days after the first dose; in another trial, the J&J vaccine had an efficacy of 74% 28 days after the first dose. Lastly, seven of eight studies found significantly increased cycle threshold, suggestive of lower viral load, in PfBnT or AZ vaccinated individuals compared with those who were unvaccinated. Conclusion: The AZ and PfBnT vaccines may prevent household transmission of COVID-19 after 14 days of vaccination. More studies have found the vaccines to significantly reduce the risk of asymptomatic infection and significantly increase cycle threshold, suggestive of lower viral load. Further research is needed to evaluate post-vaccination infectivity and transmission of both the wild type COVID-19 virus and the variants of concern from other jurisdictions.

scholarly journals Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile

2021 ◽  
Vol 7 (7) ◽  
pp. eabe6855 ◽  
Author(s):  
Carolina Beltrán-Pavez ◽  
Sebastián Riquelme-Barrios ◽  
Aarón Oyarzún-Arrau ◽  
Aracelly Gaete-Argel ◽  
Roxana González-Stegmaier ◽  
...  
Keyword(s):  
General Population ◽  
Local Level ◽  
Neutralizing Antibody ◽  
Host Immunity ◽  
Antibody Responses ◽  
Wild Type ◽  
Neutralization Activity ◽  
Future Studies

Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19–related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.

scholarly journals Screening tests for endometrial cancer in the general population

2021 ◽  
Author(s):  
Kelechi Njoku ◽  
Helena O'Flynn ◽  
Eleanor Jones ◽  
Neal C Ramchander ◽  
Helen White ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
General Population ◽  
Screening Tests

scholarly journals Risk Factors for Hepatitis C Infection Among Sexually Transmitted Disease-Infected, Inner City Obstetric Patients

2003 ◽  
Vol 11 (4) ◽  
pp. 191-198 ◽  
Author(s):  
Youyin Choy ◽  
Lisa Gittens-Williams ◽  
Joseph Apuzzio ◽  
Joan Skurnick ◽  
Carl Zollicoffer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C ◽  
High Risk ◽  
General Population ◽  
Inner City ◽  
Multiple Logistic Regression Analysis ◽  
Transmitted Disease ◽  
Screening Tests ◽  
Hepatitis C Infection ◽  
Sexually Transmitted

Objective:To test the hypothesis that our inner city obstetric patients who have been infected with sexually transmitted diseases (STDs) will have a higher prevalence of hepatitis C virus infection than the general population and to identify specific risk factors and high-risk groups.Methods:All patients in our prenatal clinic (July 1997–April 1999) who tested positive for one or more STDs were asked to return for hepatitis C antibody testing. Medical charts of all patients who returned for hepatitis C testing were reviewed.Results:A total of 106 patients with STDs were tested for hepatitis C. Positive screening tests for anti-hepatitis C antibody were found in 6.6% (7/106) of the patients (95% CI = 2.7–13.1%). This frequency is significantly higher than the hepatitis C prevalence (1.8%) in the general United States population (p= 0.006). Multiple logistic regression analysis confirmed only older age (p= 0.016) and positive HIV status (p= 0.023) to be significant predictors of hepatitis C infection.Conclusions:Inner city STD-infected obstetric patients are at high risk for hepatitis C infection compared with the general population. Increasing age and HIV-positive status are risk factors which are significantly associated with hepatitis C infection.

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 Modelling upper respiratory viral load dynamics of SARS-CoV-2

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Joseph D. Challenger ◽  
Cher Y. Foo ◽  
Yue Wu ◽  
Ada W. C. Yan ◽  
Mahdi Moradi Marjaneh ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune Responses ◽  
Mechanistic Model ◽  
Severity Of Illness ◽  
Upper Respiratory Tract ◽  
Neutralising Antibodies ◽  
Immune Mediated ◽  
Peak Viral Load ◽  
Upper Respiratory ◽  
Serial Measurements

AbstractRelationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

scholarly journals Distribution of SARS-CoV-2 PCR Cycle Threshold Values Provide Practical Insight Into Overall and Target-Specific Sensitivity Among Symptomatic Patients

2020 ◽  
Vol 154 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Blake W Buchan ◽  
Jessica S Hoff ◽  
Cameron G Gmehlin ◽  
Adriana Perez ◽  
Matthew L Faron ◽  
...  
Keyword(s):  
Viral Load ◽  
Limit Of Detection ◽  
False Negative ◽  
Age Group ◽  
Rt Pcr ◽  
Patient Age ◽  
Cycle Threshold ◽  
Negative Results ◽  
Patient Âgé ◽  
False Negative Results

Abstract Objectives We examined the distribution of reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values obtained from symptomatic patients being evaluated for coronavirus disease 2019 (COVID-19) to determine the proportion of specimens containing a viral load near the assay limit of detection (LoD) to gain practical insight to the risk of false-negative results. We also examined the relationship between CT value and patient age to determine any age-dependent difference in viral load or test sensitivity. Methods We collected CT values obtained from the cobas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay corresponding to 1,213 combined nasopharyngeal-oropharyngeal specimens obtained from symptomatic individuals that were reported as positive or presumptive positive for SARS-CoV-2. CT values were stratified by SARS-CoV target and patient age group. Results In total, 93.3% to 98.4% of specimens demonstrated CT values greater than 3× the assay LoD, at which point false-negative results would not be expected. The mean of CT values between age groups was statistically equivalent with the exception of patients in age group 80 to 89 years, which demonstrated slightly lower CTs. Conclusions Based on the distribution of observed CT values, including the small proportion of specimens with values near the assay LoD, there is a low risk of false-negative RT-PCR results in combined nasopharyngeal-oropharyngeal specimens obtained from symptomatic individuals.

scholarly journals Understanding the within-host dynamics of influenza A virus: from theory to clinical implications

2016 ◽  
Vol 13 (119) ◽  
pp. 20160289 ◽  
Author(s):  
Christoforos Hadjichrysanthou ◽  
Emilie Cauët ◽  
Emma Lawrence ◽  
Carolin Vegvari ◽  
Frank de Wolf ◽  
...  
Keyword(s):  
Viral Load ◽  
Influenza A Virus ◽  
Post Infection ◽  
Influenza A ◽  
Antiviral Drugs ◽  
Load Curve ◽  
Clinical Endpoints ◽  
Time To Peak ◽  
Infection Dynamics ◽  
Peak Viral Load

Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.

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