Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution

The global effort to vaccinate people against SARS-CoV-2 in the midst of an ongoing pandemic has raised questions about the nature of vaccine breakthrough infections and the potential for vaccinated individuals to transmit the virus. These questions have become even more urgent as new variants of concern with enhanced transmissibility, such as Delta, continue to emerge. To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

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Daily sampling of early SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness

10.1101/2021.07.12.21260208 ◽

2021 ◽

Author(s):

Ruian Ke ◽

Pamela P Martinez ◽

Rebecca L Smith ◽

Laura L Gibson ◽

Agha Mirza ◽

...

Keyword(s):

Infectious Virus ◽

Acute Infection ◽

Sampling Site ◽

Virus Shedding ◽

Individual Level ◽

Viral Loads ◽

Infection Dynamics ◽

Daily Sampling ◽

Clearance Kinetics ◽

Longitudinal Sampling

The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimate viral reproduction and clearance rates, and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Viral genome load often peaked days earlier in saliva than in nasal swabs, indicating strong compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of B.1.1.7 and non-B.1.1.7 viruses were indistinguishable, however B.1.1.7 exhibited a significantly slower pre-peak growth rate in saliva. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

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Duration of Infectious Virus Shedding in Patients With Severe Coronavirus Disease 2019 Who Required Mechanical Ventilation

10.21203/rs.3.rs-395009/v1 ◽

2021 ◽

Author(s):

Toshihito Nomura ◽

Hiroki Kitagawa ◽

Keitaro Omori ◽

Norifumi Shigemoto ◽

Masaki Kakimoto ◽

...

Keyword(s):

Mechanical Ventilation ◽

Symptom Onset ◽

Infectious Virus ◽

Quantitative Polymerase Chain Reaction ◽

University Hospital ◽

Nasopharyngeal Swab ◽

Test Results ◽

Virus Shedding ◽

Viral Culture ◽

Respiratory Management

Abstract Approximately 5% of patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 develop severe COVID-19. Severe COVID-19 requires respiratory management with mechanical ventilation and an extended period of treatment. Prolonged infectious virus shedding is a concern in severe COVID-19 cases, but few reports have examined the duration of infectious virus shedding. Therefore, we investigated the duration of infectious virus shedding in patients transferred to Hiroshima University Hospital with severe COVID-19 requiring mechanical ventilation. Nasopharyngeal swab specimens were collected and analyzed using both viral culture and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) tests between December 2020 and February 2021. Of the 23 patients tested, the proportions of those with positive test results at first specimen collection on RT-qPCR and viral culture tests were 95·7% and 30·4%, respectively. All six patients with positive viral culture test results who were followed-up tested negative 24 days after symptom onset but remained positive on RT-qPCR. The longest negative conversion time was observed in a dialysis patient on immunosuppressive drugs. This study indicated that patients with severe COVID-19 remain culture positive for ≥ 10 days after symptom onset. Additionally, immunosuppressed patients with severe COVID-19 could consider isolation for ≥ 20 days.

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Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits

Viruses ◽

10.3390/v11040381 ◽

2019 ◽

Vol 11 (4) ◽

pp. 381 ◽

Cited By ~ 4

Author(s):

W. Widagdo ◽

Nisreen M. A. Okba ◽

Mathilde Richard ◽

Dennis de Meulder ◽

Theo M. Bestebroer ◽

...

Keyword(s):

Middle East ◽

Animal Species ◽

Infectious Virus ◽

Clinical Manifestations ◽

Middle East Respiratory Syndrome ◽

Viral Rna ◽

Nasal Discharge ◽

Upper Respiratory Tract ◽

Transmission Potential ◽

Livestock Animal

Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.

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Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread

PLoS Pathogens ◽

10.1371/journal.ppat.1009196 ◽

2021 ◽

Vol 17 (1) ◽

pp. e1009196

Author(s):

Jonathon A. Siva-Jothy ◽

Pedro F. Vale

Keyword(s):

Viral Load ◽

Individual Variation ◽

Disease Transmission ◽

Genetic Background ◽

Pathogen Transmission ◽

Published Data ◽

Virus Shedding ◽

Transmission Potential ◽

Sources Of Variation ◽

Host Heterogeneity

Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunological axes, which will together impact their transmission potential. Moreover, we lack well-characterized, empirical systems that enable the quantification of individual variation in key host traits, while also characterizing genetic or sex-based sources of such variation. Here we used Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system to dissect the genetic and sex-specific sources of variation in multiple host traits that are central to pathogen transmission. Our findings show complex interactions between genetic background, sex, and female mating status accounting for a substantial proportion of variance in lifespan following infection, viral load, virus shedding, and viral load at death. Two notable findings include the interaction between genetic background and sex accounting for nearly 20% of the variance in viral load, and genetic background alone accounting for ~10% of the variance in viral shedding and in lifespan following infection. To understand how variation in these traits could generate heterogeneity in individual pathogen transmission potential, we combined measures of lifespan following infection, virus shedding, and previously published data on fly social aggregation. We found that the interaction between genetic background and sex explained ~12% of the variance in individual transmission potential. Our results highlight the importance of characterising the sources of variation in multiple host traits to understand the drivers of heterogeneity in disease transmission.

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Infectious Norovirus Is Chronically Shed by Immunocompromised Pediatric Hosts

Viruses ◽

10.3390/v12060619 ◽

2020 ◽

Vol 12 (6) ◽

pp. 619

Author(s):

Amy Davis ◽

Valerie Cortez ◽

Marco Grodzki ◽

Ronald Dallas ◽

Jose Ferrolino ◽

...

Keyword(s):

Infectious Virus ◽

Chronic Infections ◽

Vitro Assay ◽

Virus Shedding ◽

Temporal Aspects ◽

Male Patients ◽

Immunocompromised Hosts ◽

First Time

Noroviruses are a leading cause of gastroenteritis worldwide. Although infections in healthy individuals are self-resolving, immunocompromised individuals are at risk for chronic disease and severe complications. Chronic norovirus infections in immunocompromised hosts are often characterized by long-term virus shedding, but it is unclear whether this shed virus remains infectious. We investigated the prevalence, genetic heterogeneity, and temporal aspects of norovirus infections in 1140 patients treated during a 6-year period at a pediatric research hospital. Additionally, we identified 20 patients with chronic infections lasting 37 to >418 days. Using a new human norovirus in vitro assay, we confirmed the continuous shedding of infectious virus for the first time. Shedding lasted longer in male patients and those with diarrheal symptoms. Prolonged shedding of infectious norovirus in immunocompromised hosts can potentially increase the likelihood of transmission, highlighting the importance of isolation precautions to prevent nosocomial infections.

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Duration of Infectious Virus Shedding in Patients with Severe Coronavirus Disease 2019 Who Required Mechanical Ventilation

SSRN Electronic Journal ◽

10.2139/ssrn.3800855 ◽

2021 ◽

Author(s):

Toshihito Nomura ◽

Hiroki Kitagawa ◽

Keitaro Omori ◽

Norifumi Shigemoto ◽

Masaki Kakimoto ◽

...

Keyword(s):

Mechanical Ventilation ◽

Infectious Virus ◽

Virus Shedding

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Age-related susceptibility of ferrets to SARS-CoV-2 infection

10.1101/2021.08.16.456510 ◽

2021 ◽

Author(s):

Mathias Martins ◽

Maureen H.V. Fernandes ◽

Lok R Joshi ◽

Diego Diel

Keyword(s):

Respiratory Tract ◽

Viral Entry ◽

Infectious Virus ◽

Health Conditions ◽

Upper Respiratory Tract ◽

Infectious Dose ◽

Virus Shedding ◽

Age Related ◽

Upper Respiratory ◽

Effect Of Age

Susceptibility to SARS-CoV-2 and the outcome of COVID-19 have been linked to underlying health conditions and the age of affected individuals. Here we assessed the effect of age on SARS-CoV-2 infection using a ferret model. For this, young (6-month-old) and aged (18-to-39-month-old) ferrets were inoculated intranasally with various doses of SARS-CoV-2. By using infectious virus shedding in respiratory secretions and seroconversion, we estimated that the infectious dose of SARS-CoV-2 in aged animals is ~32 plaque forming units (PFU) per animal while in young animals it was estimated to be ~100 PFU. We showed that viral replication in the upper respiratory tract and shedding in respiratory secretions is enhanced in aged ferrets when compared to young animals. Similar to observations in humans, this was associated with higher expressions levels of two key viral entry factors - ACE2 and TMPRSS2 - in the upper respiratory tract of aged ferrets.

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SARS-CoV-2 Delta variant pathogenesis and host response in Syrian hamsters

10.1101/2021.07.24.453631 ◽

2021 ◽

Author(s):

Sreelekshmy Mohandas ◽

Pragya Dhruv Yadav ◽

Anita Aich Shete ◽

Dimpal Nyayanit ◽

Gajanan N Sapkal ◽

...

Keyword(s):

Lung Disease ◽

Host Response ◽

Virus Isolate ◽

Genomic Rna ◽

Hamster Model ◽

Moderate Severity ◽

Virus Shedding ◽

Transmission Potential ◽

Significant Difference ◽

Study Support

B.1.617 lineage is becoming a dominant SARS-CoV-2 lineage worldwide and was the dominant lineage reported in second COVID-19 wave in India, which necessitated studying the properties of the variant. We evaluated the pathogenicity and virus shedding of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 and compared with that of B.1, an early virus isolate with D614G mutation in Syrian hamster model. Viral load, antibody response and lung disease were studied. No significant difference in the virus shedding pattern was observed among these variants studied. A significantly high SARS-CoV-2 sub genomic RNA could be detected in the respiratory tract of hamsters infected with Delta variant for 14 days. Delta variant induced lung disease of moderate severity in 40% of infected animals. The neutralizing capability of the B.1, Delta and B.1.617.3 variant infected animals were found significantly lower with the B.1.351 (Beta variant). The findings of the study support the attributed disease severity and the increased transmission potential of the Delta variant.

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Dissecting genetic and sex-specific host heterogeneity in pathogen transmission potential

10.1101/733915 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jonathon A. Siva-Jothy ◽

Pedro F. Vale

Keyword(s):

Viral Load ◽

Disease Transmission ◽

Genetic Background ◽

Pathogen Transmission ◽

Virus Shedding ◽

Transmission Potential ◽

Individual Level ◽

Sources Of Variation ◽

Specific Variation ◽

The Individual

AbstractHeterogeneity in disease transmission is widespread and, when not accounted for, can produce unpredictable outbreaks of infectious disease. Despite this, precisely how different sources of variation in host traits drive heterogeneity in disease transmission is poorly understood. Here we dissected the sources of variation in pathogen transmission using Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system. We found that infected lifespan, viral growth, virus shedding, and viral load at death were all significantly influenced by fly genetic background, sex and female mating status. To understand how variation in each of these traits may generate heterogeneity in disease transmission, we estimated individual transmission potential by integrating data on virus shedding and lifespan alongside previously collected data on social aggregation. We found that ∼15% of between-individual heterogeneity in disease transmission was explained by a significant interaction between genetic and sex-specific variation. We also characterised the amount of variation in viral load, virus shedding, and lifespan following infection that could be explained by genetic background and sex. Amongst the determinants of individual variation in disease transmission these sources of host variation play roles of varying importance, with genetic background generally playing the largest role. Our results highlight the importance of characterising sources of variation in multiple host traits when studying disease transmission at the individual-level.

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Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers

10.1101/2021.08.20.21262158 ◽

2021 ◽

Author(s):

Marc Conrad Shamier ◽

Alma Tostmann ◽

Susanne Bogers ◽

Janet De Wilde ◽

Jeroen IJpelaar ◽

...

Keyword(s):

Health Care ◽

Health Care Workers ◽

Healthcare Workers ◽

Infectious Virus ◽

Virus Detection ◽

Lower Probability ◽

Rt Pcr ◽

Virus Shedding ◽

Care Workers ◽

Virus Culture

SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. We analyzed the virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), using RT-PCR and virus culture. The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, we demonstrate lower probability of infectious virus detection in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. We conclude that rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.

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