Dynamics of Viral Shedding and Symptoms in Patients with Asymptomatic or Mild COVID-19

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.

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Correlation of Pandemic (H1N1) 2009 Viral Load with Disease Severity and Prolonged Viral Shedding in Children

Emerging Infectious Diseases ◽

10.3201/eid1608.091918 ◽

2010 ◽

Vol 16 (8) ◽

pp. 1265-1272 ◽

Cited By ~ 77

Author(s):

Chung-Chen Li ◽

Lin Wang ◽

Hock-Liew Eng ◽

Huey-Ling You ◽

Ling-Sai Chang ◽

...

Keyword(s):

Viral Load ◽

Disease Severity ◽

Pandemic H1n1 ◽

Viral Shedding ◽

Pandemic H1n1 2009

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The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19

Life ◽

10.3390/life11020144 ◽

2021 ◽

Vol 11 (2) ◽

pp. 144

Author(s):

Daniele Focosi ◽

Marco Tuccori ◽

Massimo Franchini

Keyword(s):

Neutralizing Antibodies ◽

Passive Immunization ◽

Spike Protein ◽

Controlled Trials ◽

Disease Course ◽

Early Disease ◽

Hyperimmune Serum ◽

The Road ◽

Randomized Controlled ◽

Pros And Cons

Effective treatments specific for COVID-19 are still lacking. In the setting of passive immunotherapies based on neutralizing antibodies (nAbs), randomized controlled trials of COVID-19 convalescent plasma (CCP) anti-SARS-CoV-2 Spike protein monoclonal antibodies (mAb), which have been granted emergency use authorization, have suggested benefit in early disease course (less than 72 hours from symptoms and seronegative). Meanwhile, polyclonal immunoglobulins (i.e., hyperimmune serum), derived either from CCP donations or from animals immunized with SARS-CoV-2 antigens, are likely to become the next nAb-derived candidate. We here discuss the pros and cons of hyperimmune serum versus CCP and mAb, and summarize the ongoing clinical trials of COVID-19 hyperimmune sera.

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Risk Factors for Kaposi’s Sarcoma–Associated Herpesvirus DNA in Blood and in Saliva in Rural Uganda

Clinical Infectious Diseases ◽

10.1093/cid/ciz916 ◽

2019 ◽

Vol 71 (4) ◽

pp. 1055-1062 ◽

Cited By ~ 2

Author(s):

Angela Nalwoga ◽

Marjorie Nakibuule ◽

Vickie Marshall ◽

Wendell Miley ◽

Nazzarena Labo ◽

...

Keyword(s):

Risk Factors ◽

Viral Load ◽

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma ◽

Young Males ◽

Viral Shedding ◽

Antibody Titres ◽

Kaposi's Sarcoma Associated Herpesvirus ◽

Kaposi’S Sarcoma Associated Herpesvirus ◽

Ugandan Population

Abstract Background Detectable Kaposi’s sarcoma–associated herpesvirus (KSHV) DNA in blood and increased antibody titres may indicate KSHV reactivation, while the transmission of KSHV occurs via viral shedding in saliva. Methods We investigated the risk factors for KSHV DNA detection by real-time polymerase chain reaction in blood and by viral shedding in saliva, in 878 people aged 3 to 89 years of both sexes in a rural Ugandan population cohort. Helminths were detected using microscopy and the presence of malaria parasitaemia was identified using rapid diagnostic tests. Regression modelling was used for a statistical analysis. Results The KSHV viral load in blood did not correlate with the viral load in saliva, suggesting separate immunological controls within each compartment. The proportions of individuals with a detectable virus in blood were 23% among children aged 3–5 years and 22% among those 6–12 years, thereafter reducing with increasing age. The proportions of individuals with a detectable virus in saliva increased from 30% in children aged 3–5 years to 45% in those aged 6–12 years, and decreased subsequently with increasing age. Overall, 29% of males shed in saliva, compared to 19% of females (P = .008). Conclusions Together, these data suggest that young males may be responsible for much of the onward transmission of KSHV. Individuals with a current malaria infection had higher levels of viral DNA in their blood (P = .031), compared to uninfected individuals. This suggests that malaria may lead to KSHV reactivation, thereby increasing the transmission and pathogenicity of the virus.

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Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

Infection International ◽

10.1515/ii-2017-0021 ◽

2012 ◽

Vol 1 (3) ◽

pp. 137-145

Author(s):

Gui-lin Yang ◽

Ying-xia Liu ◽

Mu-tong Fang ◽

Wei-long Liu ◽

Xin-chun Chen ◽

...

Keyword(s):

T Cells ◽

Viral Load ◽

Cell Response ◽

Th17 Cell ◽

Influenza A ◽

H1n1 Influenza ◽

Cell Frequency ◽

Viral Loads ◽

Viral Shedding ◽

Ifn Γ

Abstract Objective To explore whether age, disease severity, cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance. Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study. Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients, respectively (P < 0.05). Moreover, the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients (P < 0.01). The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells. Additionally, the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells. Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods, which may partially be attributed to the impaired Th17 cell response.

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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18158181 ◽

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.

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Transmission dynamics of the delta variant of SARS-CoV-2 infections in Daejeon, South Korea

10.21203/rs.3.rs-934350/v1 ◽

2021 ◽

Author(s):

Hari Hwang ◽

Jun-Sik Lim ◽

Sun-Ah Song ◽

Chiara Achangwa ◽

Woobeom Sim ◽

...

Keyword(s):

South Korea ◽

Symptom Onset ◽

Credible Interval ◽

Transmission Dynamics ◽

Contact Tracing ◽

Nasopharyngeal Swab ◽

Strict Adherence ◽

Virus Shedding ◽

Viral Shedding ◽

Asymptomatic Patients

Abstract Background The delta variant of SARS-CoV-2 is now the predominant variant worldwide. However, its transmission dynamics remain unclear. Methods We analyzed all case patients in local clusters and temporal patterns of viral shedding using contact tracing data from 405 cases associated with the delta variant of SARS-CoV-2 between 22 June and 31 July 2021 in Daejeon, South Korea. Results Overall, half of the cases were aged under 19 years, and 20% were asymptomatic at the time of epidemiological investigation. We estimated the mean serial interval as 3.26 days (95% credible interval 2.92, 3.60), and 12% of the transmission occurred before symptom onset of the infector. We identified six clustered outbreaks, and all were associated with indoor facilities. In 23 household contacts, the secondary attack rate was 63% (52/82). We estimated that 15% (95% confidence interval, 13–18%) of cases seeded 80% of all local transmission. Analysis of the nasopharyngeal swab samples identified virus shedding from asymptomatic patients, and the highest viral load was observed two days after symptom onset. The temporal pattern of viral shedding did not differ between children and adults (P = 0.48). Conclusions Our findings suggest that the delta variant is highly transmissible in indoor settings and households. Rapid contact tracing, isolation of the asymptomatic contacts, and strict adherence to public health measures are needed to mitigate the community transmission of the delta variant.

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Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment

Sexual Health ◽

10.1071/sh07082 ◽

2008 ◽

Vol 5 (2) ◽

pp. 141 ◽

Cited By ~ 23

Author(s):

Kathleen Falster ◽

Linda Gelgor ◽

Ansari Shaik ◽

Iryna Zablotska ◽

Garrett Prestage ◽

...

Keyword(s):

Viral Load ◽

Antiretroviral Treatment ◽

Undetectable Viral Load ◽

Lower Proportion ◽

The Other ◽

Early Disease ◽

Community Based ◽

Disease Research ◽

Sex With Men ◽

Living With Hiv

Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. Results: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81–92%) and two large, community-based surveys in Australia (69–85% and 49–83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small. Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.

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Herpes simplex virus-2 transmission probability estimates based on quantity of viral shedding

Journal of The Royal Society Interface ◽

10.1098/rsif.2014.0160 ◽

2014 ◽

Vol 11 (95) ◽

pp. 20140160 ◽

Cited By ~ 35

Author(s):

Joshua T. Schiffer ◽

Bryan T. Mayer ◽

Youyi Fong ◽

David A. Swan ◽

Anna Wald

Keyword(s):

Herpes Simplex Virus ◽

Viral Load ◽

Herpes Simplex ◽

Genital Tract ◽

Transmission Probability ◽

Median Number ◽

Viral Shedding ◽

Probability Estimates ◽

High Utility ◽

Simplex Virus

Herpes simplex virus (HSV)-2 is periodically shed in the human genital tract, most often asymptomatically, and most sexual transmissions occur during asymptomatic shedding. It would be helpful to identify a genital viral load threshold necessary for transmission, as clinical interventions that maintain viral quantity below this level would be of high utility. However, because viral expansion, decay and re-expansion kinetics are extremely rapid during shedding episodes, it is impossible to directly measure genital viral load at the time of sexual activity. We developed a mathematical model based on reproducing shedding patterns in transmitting partners, and median number of sex acts prior to transmission in discordant couples, to estimate infectivity of single viral particles in the negative partner's genital tract. We then inferred probability estimates for transmission at different levels of genital tract viral load in the transmitting partner. We predict that transmission is unlikely at viral loads less than 10 4 HSV DNA copies. Moreover, most transmissions occur during prolonged episodes with high viral copy numbers. Many shedding episodes that result in transmission do not reach the threshold of clinical detection, because the ulcer remains very small, highlighting one reason why HSV-2 spreads so effectively within populations.

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