Trajectory of viral load in a prospective population-based cohort with incident SARS-CoV-2 G614 infection

Importance: SARS-CoV-2 viral trajectory has not been well-characterized in documented incident infections. These data will inform SARS-CoV-2 natural history, transmission dynamics, prevention practices, and therapeutic development. Objective: To prospectively characterize early SARS-CoV-2 viral shedding in persons with incident infection. Design: Prospective cohort study. Setting: Secondary data analysis from a multicenter study in the U.S. Participants: The samples derived from a randomized controlled trial of 829 community-based asymptomatic participants recently exposed (<96 hours) to persons with SARS-CoV-2. Participants collected daily mid-turbinate swabs for SARS-CoV-2 detection by polymerase-chain-reaction and symptom diaries for 14-days. Persons with negative swab for SARS-CoV-2 at baseline who developed infection during the study were included in the analysis. Exposure: Laboratory-confirmed SARS-CoV-2 infection. Main outcomes and measures: The observed SARS-CoV-2 viral shedding characteristics were summarized and shedding trajectories were examined using a piece-wise linear mixed-effects modeling. Whole viral genome sequencing was performed on samples with cycle threshold (Ct)<34. Results: Ninety-seven persons (57% women, median age 37-years) developed incident infections during 14-days of follow-up. Two-hundred fifteen sequenced samples were assigned to 15 lineages that belonged to the G614 variant. Forty-two (43%), 18(19%), and 31(32%) participants had viral shedding for 1 day, 2-6 days, and >7 days, with median peak viral load Ct of 38.5, 36.7, and 18.3, respectively. Six (6%) participants had 1-6 days of observed viral shedding with censored duration. The peak average viral load was observed on day 3 of viral shedding. The average Ct value was lower, indicating higher viral load, in persons reporting COVID-19 symptoms than asymptomatic. Using the statistical model, the median time from shedding onset to peak viral load was 1.4 days followed by a median of 9.7 days before clearance. Conclusions and Relevance: Incident SARS-CoV-2 G614 infection resulted in a rapid viral load peak followed by slower decay and positive correlation between peak viral load and shedding duration; duration of shedding was heterogeneous. This longitudinal evaluation of the SARS-CoV-2 G614 variant with frequent molecular testing may serve as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.

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

10.1101/2020.08.31.20185488 ◽

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.

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Integrated use of the GeneXpert Platform for TB, HIV and EVD Testing in Liberia

Global Journal of Medical Research ◽

10.34257/gjmrfvol20is5pg19 ◽

2020 ◽

pp. 19-30

Author(s):

Kassaye Tekie Desta ◽

John B. Dogba ◽

Julia Toomey Garbo ◽

Dedeh B. Kessely ◽

Candace B. Eastman ◽

...

Keyword(s):

Viral Load ◽

Ebola Virus ◽

Point Of Care ◽

Secondary Data ◽

Molecular Testing ◽

Virus Diseases ◽

Hiv Viral Load ◽

Immunodeficiency Virus ◽

Testing Data ◽

Disease Testing

Background: The capacity for molecular testing of the Human Immunodeficiency Virus (HIV) Viral load, Tuberculosis (TB) and epidemic- prone disease was very limited in Liberia prior to the Ebola Virus Diseases (EVD) outbreak. The use of point of care and near point of care machines for multiple disease testing of HIV, TB and EVD was adopted as a solution to these challenges. The purpose of this study was to evaluate the integrated use of GeneXpert for the three disease testing. Methods: A previously collected and reported GeneXpert testing data was used to evaluate the integrated use of the GeneXpert platform for TB, HIV viral load and EVD testing. All the laboratory GeneXpert secondary data available since the machines were installed and started testing were analyzed.

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Infection patterns of endemic human coronaviruses in rural households in coastal Kenya

10.1101/2020.11.03.20225441 ◽

2020 ◽

Author(s):

Dickson Machira Nyaguthii ◽

Grieven P. Otieno ◽

Ivy K. Kombe ◽

Dorothy Koech ◽

Martin Mutunga ◽

...

Keyword(s):

Viral Load ◽

School Age Children ◽

School Age ◽

Viral Shedding ◽

Peak Viral Load ◽

Rural Kenya ◽

Coronavirus Infection ◽

Polymerase Chain ◽

Human Coronaviruses ◽

Index Cases

AbstractIntroductionThe natural history and transmission patterns of endemic human coronaviruses are of increased interest following the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).MethodsIn rural Kenya 483 individuals from 47 households were followed for six months (2009-10) with nasopharyngeal swabs collected twice weekly regardless of symptoms. A total of 16,918 swabs were tested for human coronavirus (hCoV) OC43, NL63 and 229E and other respiratory viruses using polymerase chain reaction.ResultsFrom 346 (71.6%) household members 629 hCoV infection episodes were defined with 36.3% being symptomatic: varying by hCoV type and decreasing with age. Symptomatic episodes (aHR=0.6 (95% CI:0.5-0.8) or those with elevated peak viral load (medium aHR=0.4 (0.3-0.6); high aHR=0.31 (0.2-0.4)) had longer viral shedding compared to their respective counterparts. Homologous reinfections were observed in 99 (19.9%) of 497 first infections. School-age children (55%) were the most common index cases with those having medium (aOR=5.3 (2.3 – 12.0)) or high (8.1 (2.9 - 22.5)) peak viral load most often generating secondary cases.ConclusionHousehold coronavirus infection was common, frequently asymptomatic and mostly introduced by school-age children. Secondary transmission was influenced by viral load of index cases. Homologous-type reinfection was common. These data may be insightful for SARS-CoV-2.

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Early-Morning vs Spot Posterior Oropharyngeal Saliva for Diagnosis of SARS-CoV-2 Infection: Implication of Timing of Specimen Collection for Community-Wide Screening

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa210 ◽

2020 ◽

Vol 7 (6) ◽

Cited By ~ 5

Author(s):

Derek Ling-Lung Hung ◽

Xin Li ◽

Kelvin Hei-Yeung Chiu ◽

Cyril Chik-Yan Yip ◽

Kelvin Kai-Wang To ◽

...

Keyword(s):

Viral Load ◽

Diagnostic Yield ◽

Statistical Significance ◽

Early Morning ◽

Optimal Timing ◽

Molecular Testing ◽

Upper Respiratory Tract ◽

Community Screening ◽

Time Points ◽

Viral Shedding

Abstract Background Posterior oropharyngeal saliva is increasingly recognized as a valid respiratory specimen for SARS-CoV-2 diagnosis. It is easy to collect and suitable for community-wide screening. The optimal timing of collection is currently unknown, and we speculate that an early-morning specimen before oral hygiene and breakfast would increase the diagnostic yield. Methods Posterior oropharyngeal saliva was collected at 5 different time points within the same day from 18 patients with previously confirmed SARS-CoV-2 infection by molecular testing. Cycle threshold (Ct) values were compared. Results There was an overall trend of lower Ct values from specimens collected in the early morning, with a gradual decrease of viral load towards nighttime, but reaching statistical significance only when compared with the specimens collected at bedtime. Eight out of 13 subjects had a higher viral load in the early morning than the rest of the 4 time points (before lunch, before teatime at 3 pm, before dinner, before bedtime). Conclusions The result suggests a diurnal variation of viral shedding from the upper respiratory tract with a trend showing higher viral load in the early morning. For community screening purposes, posterior oropharyngeal saliva could be taken throughout the day, but preferably in the early morning to maximize the yield.

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Integrated Use of the GeneXpert Platform for TB, HIV and EVD testing in Liberia

10.21203/rs.2.16220/v1 ◽

2019 ◽

Author(s):

Kassaye Tekie Desta ◽

John B. Dogba ◽

Julia Toomey Garbo ◽

Dedeh B. Kessely ◽

Candace B. Eastman ◽

...

Keyword(s):

Viral Load ◽

Ebola Virus ◽

Point Of Care ◽

Scale Up ◽

Secondary Data ◽

Molecular Testing ◽

Hiv Viral Load ◽

Observation Report ◽

Immunodeficiency Virus ◽

Integrated Testing

Abstract Background: The capacity for molecular testing of Human Immunodeficiency Virus (HIV) Viral load, Tuberculosis (TB) and epidemic prone disease was very limited in Liberia prior to the Ebola Virus Diseases (EVD) outbreak. The use of point of care and near point of care machines for multiple disease testing of HIV, TB and EVD was adopted as a solution to these challenges. The purpose of this study was to evaluate the integrated use of the GeneXpert for the three diseases testing. Methods: A previously collected and reported GeneXpert testing data was used to evaluate the integrated use of GeneXpert platform for TB, HIV viral load and EVD testing. All the laboratory GeneXpert secondary data available since the machines were installed and started testing were analyzed. Besides; Field observation report on the operation, coordination and impact of the integrated testing was included. Results: The integrated testing of HIV Viral load, Mycobacterium Tuberculosis/Rifampicin (MTB/RIF) and EVD using the GeneXpert platform has played a significant role in Liberia. A total of 706 HIV viral load, 3695 MTB/RIF and 2309 EVD GeneXpert tests were conducted since the start of the integrated testing. Conclusion: The integrated use of the GeneXpert platform for TB, HIV and EVD is very crucial as it helped in enhancing the services and coordinating resources in a sustainable way. Lessons learnt from this integration will help to effectively scale up the integrated testing.

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Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial.

10.1101/2021.05.31.21258081 ◽

2021 ◽

Author(s):

Asaf Biber ◽

Michal Mandelboim ◽

Geva Harmelin ◽

Dana Lev ◽

Li Ram ◽

...

Keyword(s):

Viral Load ◽

Early Stage ◽

Controlled Trial ◽

Nasopharyngeal Swab ◽

Multivariable Logistic Regression Model ◽

Double Blind ◽

Viral Shedding ◽

Viral Culture ◽

Culture Viability ◽

Double Blinded

Background: Ivermectin, an antiparasitic agent, also has antiviral properties. Our aim was to assess whether ivermectin can shorten the viral shedding in patients at an early stage of COVID19 infection. Methods: The double blinded trial compared patients receiving ivermectin 0.2 mg/kg for 3 days vs. placebo in non-hospitalized COVID19 patients. RT-PCR from a nasopharyngeal swab was obtained at recruitment and then every two days. Primary endpoint was reduction of viral-load on the 6th day (third day after termination of treatment) as reflected by Ct level>30 (non-infectious level). The primary outcome was supported by determination of viral culture viability. Results: Eighty nine patients were eligible (47 in ivermectin and 42 in placebo arm). Their median age was 35 years. Females accounted for 21.6%, and 16.8% were asymptomatic at recruitment. Median time from symptom onset was 4 days. There were no statistical differences in these parameters between the two groups. On day 6, 34 out of 47 (72%) patients in the ivermectin arm reached the endpoint, compared to 21/ 42 (50%) in the placebo arm (OR 2.62; 95% CI: 1.09 to 6.31). In a multivariable logistic regression model, the odds of a negative test at day 6 was 2.62 time higher in the ivermectin group (95% CI: 1.06 to 6.45). Cultures at days 2 to 6 were positive in 3/23 (13.0%) of ivermectin samples vs. 14/29 (48.2%) in the placebo group (p=0.008). Conclusions: There were significantly lower viral loads and viable cultures in the ivermectin group, which could lead to shortening isolation time in these patients.

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Wrong person, place and time: viral load and contact network structure predict SARS-CoV-2 transmission and super-spreading events

10.1101/2020.08.07.20169920 ◽

2020 ◽

Cited By ~ 9

Author(s):

Ashish Goyal ◽

Daniel B Reeves ◽

E. Fabian Cardozo-Ojeda ◽

Joshua T Schiffer ◽

Bryan T. Mayer

Keyword(s):

Viral Load ◽

High Viral Load ◽

Physical Contact ◽

Therapeutic Interventions ◽

Contact Network ◽

Infected Person ◽

Infected People ◽

Viral Shedding ◽

Secondary Infections ◽

Peak Viral Load

SARS-CoV-2 is difficult to contain because many transmissions occur during the pre-symptomatic phase of infection. Moreover, in contrast to influenza, while most SARS-CoV-2 infected people do not transmit the virus to anybody, a small percentage secondarily infect large numbers of people. We designed mathematical models of SARS-CoV-2 and influenza which link observed viral shedding patterns with key epidemiologic features of each virus, including distributions of the number of secondary cases attributed to each infected person (individual R0) and the duration between symptom onset in the transmitter and secondarily infected person (serial interval). We identify that people with SARS-CoV-2 or influenza infections are usually contagious for fewer than one day congruent with peak viral load several days after infection, and that transmission is unlikely below a certain viral load. SARS-CoV-2 super-spreader events with over 10 secondary infections occur when an infected person is briefly shedding at a very high viral load and has a high concurrent number of exposed contacts. The higher predisposition of SARS-CoV-2 towards super-spreading events is not due to its 1-2 additional weeks of viral shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks than a person infected with influenza, likely due to aerosolization of virus. Our results support policies that limit crowd size in indoor spaces and provide viral load benchmarks for infection control and therapeutic interventions intended to prevent secondary transmission.

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Infection patterns of endemic human coronaviruses in rural households in coastal Kenya

Wellcome Open Research ◽

10.12688/wellcomeopenres.16508.1 ◽

2021 ◽

Vol 6 ◽

pp. 27

Author(s):

Dickson Machira Nyaguthii ◽

Grieven P. Otieno ◽

Ivy K. Kombe ◽

Dorothy Koech ◽

Martin Mutunga ◽

...

Keyword(s):

Viral Load ◽

School Age Children ◽

School Age ◽

Viral Shedding ◽

Peak Viral Load ◽

Rural Kenya ◽

Coronavirus Infection ◽

Polymerase Chain ◽

Human Coronaviruses ◽

Index Cases

Background: The natural history and transmission patterns of endemic human coronaviruses are of increased interest following the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods: In rural Kenya 483 individuals from 47 households were followed for six months (2009-10) with nasopharyngeal swabs collected twice weekly regardless of symptoms. A total of 16,918 swabs were tested for human coronavirus (hCoV) OC43, NL63 and 229E and other respiratory viruses using polymerase chain reaction. Results: From 346 (71.6%) household members, 629 hCoV infection episodes were defined, with 36.3% being symptomatic: varying by hCoV type and decreasing with age. Symptomatic episodes (aHR=0.6 (95% CI:0.5-0.8) or those with elevated peak viral load (medium aHR=0.4 (0.3-0.6); high aHR=0.31 (0.2-0.4)) had longer viral shedding compared to their respective counterparts. Homologous reinfections were observed in 99 (19.9%) of 497 first infections. School-age children (55%) were the most common index cases with those having medium (aOR=5.3 (2.3 – 12.0)) or high (8.1 (2.9 - 22.5)) peak viral load most often generating secondary cases. Conclusion: Household coronavirus infection was common, frequently asymptomatic and mostly introduced by school-age children. Secondary transmission was influenced by viral load of index cases. Homologous-type reinfection was common. These data may be insightful for SARS-CoV-2.

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A Phase 2 randomized, double-blind, placebo-controlled trial of the monoclonal antibody MHAA4549A in patients with acute uncomplicated influenza A infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab630 ◽

2021 ◽

Author(s):

Jeremy J Lim ◽

Sadia Dar ◽

Dirk Venter ◽

Juan P Horcajada ◽

Priya Kulkarni ◽

...

Keyword(s):

Monoclonal Antibody ◽

Viral Load ◽

Median Time ◽

Influenza A ◽

Controlled Trial ◽

Human Monoclonal Antibody ◽

Phase 2 ◽

Double Blind ◽

Double Blind Placebo ◽

Viral Shedding

Abstract Background MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer challenge studies. We investigated MHAA4549A safety and tolerability, efficacy, and pharmacokinetics in outpatients with acute, uncomplicated influenza A infection. Methods This was a Phase 2, randomized, double-blind, placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg MHAA4549A, or IV placebo in adult outpatients testing positive for influenza A. Patients were enrolled across 35 sites in 6 countries. Randomization and dosing occurred ≤ 72 hours of symptom onset; study duration was 14 weeks. The primary endpoint was the nature and frequency of adverse events (AEs). Secondary endpoints included median time to alleviation of all influenza symptoms, effects on nasopharyngeal viral load and duration of viral shedding, and MHAA4549A serum pharmacokinetics. Results Of 125 randomized patients, 124 received study treatment, with 99 confirmed positive for influenza A by central testing. Frequency of AEs between MHAA4549A and placebo groups was similar; nausea was most common (8 patients; 6.5%). MHAA4549A serum exposure was confirmed in all MHAA4549A-treated patients and was dose proportional. No hospitalizations or deaths occurred. Between MHAA4549A and placebo groups, no statistically significant differences occurred in median time to alleviation of all symptoms, nasopharyngeal viral load, or duration of viral shedding. Conclusions While MHAA4549A was safe and well-tolerated with confirmed exposure, the antibody did not improve clinical outcomes in patients with acute uncomplicated influenza A infection.

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Viral dynamic modeling of SARS-CoV-2 in non-human primates

10.21203/rs.3.rs-50301/v1 ◽

2020 ◽

Author(s):

Antonio Gonçalves ◽

Pauline Maisonnasse ◽

Flora Donati ◽

Mélanie Albert ◽

Sylvie Behillil ◽

...

Keyword(s):

Viral Load ◽

Clinical Signs ◽

Basic Number ◽

Human Infection ◽

Viral Dynamics ◽

Viral Production ◽

Viral Shedding ◽

Cynomolgus Macaques ◽

Peak Viral Load ◽

Infected Cells

Abstract Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques infected with 106 pfu of SARS-CoV-2 for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large daily viral production (>104 virus) and a within-host reproductive basic number of 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly cleared with a half-life of 9 hours, with no significant association between cytokine elevation and clearance. Translating our model to the context of human-to-human infection, human mild infection may be characterized by a peak occurring 4 days after infection, a viral shedding of ~11 days and a generation time of 4 days. These results improve the understanding of SARS-CoV-2 viral replication and better understand the infection to SARS-CoV-2 in humans.

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