Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets.
Ontology highlight
ABSTRACT:
SUBMITTER: Vaidya NK
PROVIDER: S-EPMC8402735 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The relationship between transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the amount of virus present in the proximity of a susceptible host is not understood. Here, we developed a within-host and aerosol mathematical model and used it to determine the relationship between viral kinetics in the upper respiratory track, viral kinetics in the aerosols, and new transmissions in golden hamsters challenged with SARS-CoV-2. We determined that infectious virus shedding early in infection correlates with transmission events, shedding of infectious virus diminishes late in the infection, and high viral RNA levels late in the infection are a poor indicator of transmission. We further showed that viral infectiousness increases in a density dependent manner with viral RNA and that their relative ratio is time-dependent. Such information is useful for designing interventions.
| S-EPMC9371288 | biostudies-literature
Project description:The global evolution of SARS-CoV-2 depends in part upon the evolutionary dynamics within individual hosts with varying immune histories. To characterize the within-host evolution of acute SARS-CoV-2 infection, we sequenced saliva and nasal samples collected daily from vaccinated and unvaccinated individuals early during infection. We show that longitudinal sampling facilitates high-confidence genetic variant detection and reveals evolutionary dynamics missed by less-frequent sampling strategies. Within-host dynamics in both unvaccinated and vaccinated individuals appeared largely stochastic; however, in rare cases, minor genetic variants emerged to frequencies sufficient for forward transmission. Finally, we detected significant genetic compartmentalization of viral variants between saliva and nasal swab sample sites in many individuals. Altogether, these data provide a high-resolution profile of within-host SARS-CoV-2 evolutionary dynamics.IMPORTANCEWe detail the within-host evolutionary dynamics of SARS-CoV-2 during acute infection in 31 individuals using daily longitudinal sampling. We characterized patterns of mutational accumulation for unvaccinated and vaccinated individuals, and observed that temporal variant dynamics in both groups were largely stochastic. Comparison of paired nasal and saliva samples also revealed significant genetic compartmentalization between tissue environments in multiple individuals. Our results demonstrate how selection, genetic drift, and spatial compartmentalization all play important roles in shaping the within-host evolution of SARS-CoV-2 populations during acute infection.
| S-EPMC10805032 | biostudies-literature
Project description:BackgroundCOVID-19 infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause mild symptoms to severe illness and death. Co-infections of SARS-CoV-2 with other respiratory viruses have been described. However, two SARS-CoV-2 lineage co-infection have been rarely reported.MethodologyA genotyping analysis and two different types of whole genome sequencing were performed (Illumina MiniSeq and ONT MinION). When examining the phylogenetic analysis in NextClade and Pangolin webservers, and considering the genotyping findings, conflicting results were obtained.ResultsThe raw data of the sequencing was analyzed, and nucleotide variants were identified between different reads of the virus genome. B.1 and P.1 lineages were identified within the same sample.ConclusionsWe concluded that this is a co-infection case with two SARS-CoV-2 lineages, the first one reported in Ecuador.
| S-EPMC9259011 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and causing the global coronavirus pandemic. The viral dynamics of SARS-CoV-2 infection have not been quantitatively investigated. In this paper, we use mathematical models to study the pathogenic features of SARS-CoV-2 infection by examining the interaction between the virus, cells and immune responses. Models are fit to the data of SARS-CoV-2 infection in patients and non-human primates. Data fitting and numerical simulation show that viral dynamics of SARS-CoV-2 infection have a few distinct stages. In the initial stage, viral load increases rapidly and reaches the peak, followed by a plateau phase possibly generated by lymphocytes as a secondary target of infection. In the last stage, viral load declines due to the emergence of adaptive immune responses. When the initiation of seroconversion is late or slow, the model predicts viral rebound and prolonged viral persistence, consistent with the observation in non-human primates. Using the model we also evaluate the effect of several potential therapeutic interventions for SARS-CoV-2 infection. Model simulation shows that anti-inflammatory treatments or antiviral drugs combined with interferon are effective in reducing the duration of the viral plateau phase and diminishing the time to recovery. These results provide insights for understanding the infection dynamics and might help develop treatment strategies against COVID-19.
| S-EPMC7409942 | biostudies-literature
Project description:Nonpharmaceutical interventions (NPIs) to contain the SARS-CoV-2 pandemic drastically reduced human-to-human interactions, decreasing the circulation of other respiratory viruses, as well. Consequently, influenza virus circulation, which is normally responsible for 3 to 5 million hospitalizations per year globally, was significantly reduced. With the downscaling of the NPI countermeasures, there is a concern for increased influenza disease, particularly in individuals suffering from postacute effects of SARS-CoV-2 infection. To investigate this, we performed a sequential influenza H1N1 infection 4 weeks after an initial SARS-CoV-2 infection in ferrets. Upon H1N1 infection, ferrets that were previously infected with SARS-CoV-2 showed an increased tendency to develop clinical signs, compared to the control H1N1-infected animals. A histopathological analysis indicated only a slight increase for type II pneumocyte hyperplasia and bronchitis. Thus, the effects of the sequential infection appeared minor. However, ferrets were infected with B.1.351-SARS-CoV-2, the beta variant of concern, which replicated poorly in our model. The histopathology of the respiratory organs was mostly resolved 4 weeks after the SARS-CoV-2 infection, with only reminiscent histopathological features in the upper respiratory tract. Nevertheless, SARS-CoV-2 specific cellular and humoral responses were observed, confirming an established infection. On account of a modest trend toward the enhancement of the influenza disease, even upon a mild SARS-CoV-2 infection, our findings suggest that a stronger SARS-CoV-2 infection and its consequent, long-term effects could have a greater impact on the outcome of disease after a sequential influenza infection. Hence, the influenza vaccination of individuals suffering from postacute SARS-CoV-2 infection effects may be considered an avertible measure for such a scenario. IMPORTANCE During the COVID-19 pandemic, the use of face masks, social distancing, and isolation were effective not only in decreasing the circulation of SARS-CoV-2 but also in reducing other respiratory viruses, such as influenza. With fewer restrictions currently in place, influenza is slowly returning. In the meantime, people who are still suffering from long-COVID could be more vulnerable to an influenza virus infection and could develop a more severe influenza disease. This study provides directions to the effect of a previous SARS-CoV-2 exposure on influenza disease severity in a ferret model. This model is highly valuable to test sequential infections under controlled settings for translation to humans. We could not induce clear long-term COVID-19 effects, as the SARS-CoV-2 infections in the ferrets were mild. However, we still observed a slight increase in influenza disease severity compared to ferrets that had not encountered SARS-CoV-2 before. Therefore, it may be advisable to include long-COVID patients as a risk group for influenza vaccination.
| S-EPMC9784775 | biostudies-literature
Project description:Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.
| S-EPMC3386161 | biostudies-literature
Project description:To further investigate the underlying mechanisms of severe acute respiratory syndrome (SARS) pathogenesis and evaluate the therapeutic efficacy of potential drugs and vaccines it is necessary to use an animal model that is highly representative of the human condition in terms of respiratory anatomy, physiology and clinical sequelae. The ferret, Mustela putorius furo, supports SARS-CoV replication and displays many of the symptoms and pathological features seen in SARS-CoV-infected humans. We have recently established a SARS-CoV infection-challenge ferret platform for use in evaluating potential therapeutics to treat SARS. The main objective of the current study was to extend our previous results and identify early host immune responses upon infection and determine immune correlates of protection upon challenge with SARS-CoV in ferrets. Keywords: time course This study is a simple time course (58 day) examination of host responses in 35 SARS-CoV (TOR2) infected ferrets with the addition of a challenge inoculation of SARS CoV (TOR2) at day 29 post infection. Three mock-infected ferrets are included as negative controls. Due to the unavailability of ferret microarrays, Affymetrix Canine 2.0 oligonucleotide arrays were chosen following sequence analysis of our ferret cDNA library (~5000 clones) and demonstration of high levels of homology (>80%) between dog and ferret.
2013-05-28 | E-GEOD-11704 | biostudies-arrayexpress
Project description:We found severe acute respiratory syndrome coronavirus 2 RNA in 6 (8.4%) of 71 ferrets in central Spain and isolated and sequenced virus from 1 oral and 1 rectal swab specimen. Natural infection occurs in kept ferrets when virus circulation among humans is high. However, small ferret collections probably cannot maintain virus circulation.
| S-EPMC8237878 | biostudies-literature
Project description:While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) shows higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.
2021-12-31 | GSE189619 | GEO
Project description:Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outcome of coronavirus disease 2019 (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 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 compared to young animals. Similar to observations in humans, this was associated with higher transcription levels of two key viral entry factors, ACE2 and TMPRSS2, in the upper respiratory tract of aged ferrets. IMPORTANCE In humans, ACE2 and TMPRSS2 are expressed in various cells and tissues, and differential expression has been described in young and old people, with a higher level of expressing cells being detected in the nasal brushing of older people than young individuals. We described the same pattern occurring in ferrets, and we demonstrated that age affects susceptibility of ferrets to SARS-CoV-2. Aged animals were more likely to get infected when exposed to lower infectious dose of the virus than young animals, and the viral replication in the upper respiratory tract and shedding are enhanced in aged ferrets. Together, these results suggest that the higher infectivity and enhanced ability of SARS-CoV-2 to replicate in aged individuals is associated, at least in part, with transcription levels of ACE2 and TMPRSS2 at the sites of virus entry. The young and aged ferret model developed here may represent a great platform to assess age-related differences in SARS-CoV-2 infection dynamics and replication.
| S-EPMC8826803 | biostudies-literature