scholarly journals Transmission and protection against re-infection in the ferret model with the SARS-CoV-2 USA-WA1/2020 reference isolate

2021 ◽  
Author(s):  
Devanshi R. Patel ◽  
Cassandra J. Field ◽  
Kayla M. Septer ◽  
Derek G. Sim ◽  
Matthew J. Jones ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Direct Contact ◽  
Reference Strain ◽  
Infectious Virus ◽  
Natural Infection ◽  
Upper Respiratory Tract ◽  
Nasal Wash ◽  
The Usa ◽  
Upper Respiratory ◽  
Mode Of Transmission

SARS-CoV-2 has initiated a global pandemic and several vaccines have now received emergency use authorization. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semi-permissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of vRNA at multiple timepoints, direct contact transmission was efficient to 3/3 and 3/4 contact animals in two respective studies, while respiratory droplet transmission was poor to only 1/4 contact animals. To determine if previously infected ferrets were protected against re-infection, ferrets were re-challenged 28 or 56 days post-infection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets, ferrets were vaccinated using a prime-boost strategy with the S-protein receptor-binding domain formulated with an oil-in-water adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined these studies demonstrate that in ferrets direct contact is the predominant mode of transmission of the USA-WA1/2020 isolate and immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity. Importance: The SARS-CoV-2 USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories. Here, we show the predominant mode of transmission of this isolate in ferrets is by direct contact. We further demonstrate ferrets are protected against re-infection for at least 56 days even when levels of neutralizing antibodies are low or undetectable. Last, we show that when ferrets were vaccinated by the intramuscular route to induce antibodies against SARS-CoV-2, ferrets remain susceptible to infection of the upper respiratory tract. Collectively, these studies suggest protection of the upper respiratory tract will require vaccine approaches that mimic natural infection.

scholarly journals Transmission and protection against re-infection in the ferret model with the SARS-CoV-2 USA-WA1/2020 reference isolate

2020 ◽  
Author(s):  
Devanshi R. Patel ◽  
Cassandra J. Field ◽  
Kayla M. Septer ◽  
Derek G. Sim ◽  
Matthew J. Jones ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Direct Contact ◽  
Primary Infection ◽  
Reference Strain ◽  
Infectious Virus ◽  
Natural Infection ◽  
Upper Respiratory Tract ◽  
Nasal Wash ◽  
Upper Respiratory ◽  
Mode Of Transmission

AbstractSARS-CoV-2 has initiated a global pandemic and vaccines are being rapidly developed. Using the reference strain SARS-CoV-2 USA-WA1/2020, we evaluated modes of transmission and the ability of prior infection or vaccine-induced immunity to protect against infection in ferrets. Ferrets were semi-permissive to infection with the USA-WA1/2020 isolate. When transmission was assessed via the detection of vRNA at multiple timepoints, direct contact transmission was efficient to 3/3 and 3/4 contact animals in two respective studies, while respiratory transmission was poor to only 1/4 contact animals. To assess the durability of immunity, ferrets were re-challenged 28 or 56 days post-primary infection. Following viral challenge, no infectious virus was recovered in nasal wash samples. In addition, levels of vRNA in the nasal wash were several orders of magnitude lower than during primary infection, and vRNA was rapidly cleared. To determine if intramuscular vaccination protected ferrets against infection, ferrets were vaccinated using a prime-boost strategy with the S-protein receptor-binding domain formulated with an oil-in-water adjuvant. Upon viral challenge, none of the mock or vaccinated animals were protected against infection, and there were no significant differences in vRNA or infectious virus titers in the nasal wash. Combined these studies demonstrate that in ferrets direct contact is the predominant mode of transmission of the SARS-CoV-2 USA-WA1/2020 isolate and immunity to SARS-CoV-2 is maintained for at least 56 days. Our studies also indicate protection of the upper respiratory tract against SARS-CoV-2 will require vaccine strategies that mimic natural infection or induce site-specific immunity.ImportanceThe SARS-CoV-2 USA-WA1/2020 strain is a CDC reference strain used by multiple research laboratories. Here, we show the predominant mode of transmission of this isolate in ferrets is by direct contact. We further demonstrate ferrets are protected against re-infection for at least 56 days even when levels of neutralizing antibodies are low or undetectable. Last, we show that when ferrets were vaccinated by the intramuscular route to induce antibodies against SARS-CoV-2, ferrets remain susceptible to infection of the upper respiratory tract. Collectively, these studies suggest protection of the upper respiratory tract will require vaccine approaches that mimic natural infection.

scholarly journals Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models

2021 ◽  
pp. eabh0755
Author(s):  
Neeltje van Doremalen ◽  
Jyothi N. Purushotham ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Trenton Bushmaker ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Direct Contact ◽  
Infectious Virus ◽  
Rhesus Macaques ◽  
Upper Respiratory Tract ◽  
Preclinical Models ◽  
Viral Loads ◽  
Viral Shedding ◽  
Nasal Swabs ◽  
Upper Respiratory

ChAdOx1 nCoV-19/AZD1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently being deployed globally. Previous studies in rhesus macaques revealed that intramuscular vaccination with ChAdOx1 nCoV-19/AZD1222 provided protection against pneumonia but did not reduce shedding of SARS-CoV-2 from the upper respiratory tract. Here, we investigated whether intranasally administered ChAdOx1 nCoV-19 reduces detection of virus in nasal swabs after challenging vaccinated macaques and hamsters with SARS-CoV-2 carrying a D614G mutation in the spike protein. Viral loads in swabs obtained from intranasally vaccinated hamsters were decreased compared to control hamsters, and no viral RNA or infectious virus was found in lung tissue after a direct challenge or after direct contact with infected hamsters. Intranasal vaccination of rhesus macaques resulted in reduced virus concentrations in nasal swabs and a reduction in viral loads in bronchoalveolar lavage and lower respiratory tract tissue. Intranasal vaccination with ChAdOx1 nCoV-19/AZD1222 reduced virus concentrations in nasal swabs in two different SARS-CoV-2 animal models, warranting further investigation as a potential vaccination route for COVID-19 vaccines.

scholarly journals Studies on the pathogenesis of rinderpest in experimental cattle: IV. Proliferation of the virus following contact infection

1965 ◽  
Vol 63 (4) ◽  
pp. 497-506 ◽  
Author(s):  
W. P. Taylor ◽  
W. Plowright ◽  
R. Pillinger ◽  
C. S. Rampton ◽  
R. F. Staple
Keyword(s):  
Lymph Node ◽  
Respiratory Tract ◽  
Lymph Nodes ◽  
Natural Infection ◽  
Kidney Tissue ◽  
Lung Parenchyma ◽  
Published Data ◽  
Upper Respiratory Tract ◽  
Virus Content ◽  
Upper Respiratory

Cattle were infected with rinderpest virus by housing them for 24 hr. in stalls containing donor animals which had been reacting to the disease for 3–5 days. They were then transferred to individual clean stalls and killed on the 2nd to 10th days following first exposure. Various tissues were collected, particularly those of the upper and lower respiratory tracts, and their virus content was estimated in calf-kidney tissue cultures.Virus was recovered from 15 of 35 animals tested and in eight of these generalization had occurred, although only two had begun to show a pyrexial response. The stage of the infection could not be predicted from the time that had elapsed following exposure, since early, limited proliferation was encountered on the 3rd to the 10th days.It was considered that seven animals gave indications of the pathways by which natural infection had occurred. In each of these virus proliferation was established very early in the pharyngeal lymph node; in three the submaxillary lymph node was similarly involved and in four the palatal tonsil. It was suggested that these data probably indicated that infection always occurred via the upper respiratory tract.In three cases virus titres were highest in the bronchial or costocervical lymph nodes; this was construed as evidence for the additional involvement of the lower respiratory tract in primary infection.No infectivity could be demonstrated in the mucosae or lung parenchyma associated with the above-mentioned lymph nodes and this, together with previously published data, was accepted as strong presumptive evidence that the infecting virus passes through the mucosae without producing a local lesion or proliferating there. These results were compared briefly with those of Bedson & Duckworth (1963) for rabbit pox.

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

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.

scholarly journals THE BEHAVIOR OF POX VIRUSES IN THE RESPIRATORY TRACT

1941 ◽  
Vol 74 (3) ◽  
pp. 203-212 ◽  
Author(s):  
John B. Nelson
Keyword(s):  
Respiratory Tract ◽  
Direct Contact ◽  
Subsequent Development ◽  
Skin Lesions ◽  
Upper Respiratory Tract ◽  
Complete Protection ◽  
Mucosal Changes ◽  
Upper Respiratory ◽  
Nasal Passages ◽  
Reduced Activity

Fowl pox virus from active skin lesions was established in the upper respiratory tract of normal chickens by nasal instillation and maintained for 12 successive passages. The nasal infection was not communicable by direct contact but did afford protection, for at least 6 weeks, against subsequent development of the virus in the skin. Multiplication of the virus in the nasal passages was only irregularly attended by specific mucosal changes and was not accompanied by the vigorous counter-reaction engendered by the causal agents of roup. The same strain of virus on propagation in embryonated eggs also survived and multiplied in the nasal tract but with somewhat reduced activity, the 34th egg transfer failing to afford complete protection. Nasal instillation in mice was followed only by a reaction in the lung from which the virus was recoverable through the 7th day.

scholarly journals SARS-CoV-2 Infections in mRNA Vaccinated Individuals are Biased for Viruses Encoding Spike E484K and Associated with Reduced Infectious Virus Loads that Correlate with Respiratory Antiviral IgG levels.

2021 ◽  
Author(s):  
Heba H Mostafa ◽  
chun Huai Luo ◽  
C. Paul Morris ◽  
Maggie Li ◽  
Nicholas J Swanson ◽  
...  
Keyword(s):  
Cell Culture ◽  
Respiratory Tract ◽  
Large Scale ◽  
Infectious Virus ◽  
Time Frame ◽  
Molecular Testing ◽  
Upper Respiratory Tract ◽  
Symptomatic Infection ◽  
Viral Loads ◽  
Upper Respiratory

Abstract Introduction COVID-19 large scale immunization in the US has been associated with infrequent breakthrough positive molecular testing. Whether a positive test is associated with a high viral RNA load, specific viral variant, recovery of infectious virus, or symptomatic infection is largely not known. Methods In this study, we identified 133 SARS-CoV-2 positive patients who had received two doses of either Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) vaccines, the 2nd of which was received between January and April of 2021. The positive samples were collected between January and May of 2021 with a time that extended from 2 to 100 days after the second dose. Samples were sequenced to characterize the whole genome and Spike protein changes and cycle thresholds that reflect viral loads were determined using a single molecular assay. Local SARS-CoV-2 IgG antibodies were examined using ELISA and specimens were grown on cell culture to assess the recovery of infectious virus as compared to a control unvaccinated cohort from a matched time frame. Results Of 133 specimens, 24 failed sequencing and yielded a negative or very low viral load on the repeat PCR. Of 109 specimens that were used for further genome analysis, 68 (62.4%) were from symptomatic infections, 11 (10.1%) were admitted for COVID-19, and 2 (1.8%) required ICU admission with no associated mortality. The predominant virus variant was the alpha (B.1.1.7), however a significant association between lineage B.1.526 and amino acid change S: E484K with positives after vaccination was noted when genomes were compared to a large control cohort from a matched time frame. A significant reduction of the recovery of infectious virus on cell culture as well as delayed time to the first appearance of cytopathic effect was accompanied by an increase in local IgG levels in respiratory samples of vaccinated individuals but upper respiratory tract IgG levels were not different between symptomatic or asymptomatic infections. Conclusions Vaccination reduces the recovery of infectious virus in breakthrough infections accompanied by an increase in upper respiratory tract local immune responses.

scholarly journals Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

2020 ◽  
Vol 25 (32) ◽  
Author(s):  
Anika Singanayagam ◽  
Monika Patel ◽  
Andre Charlett ◽  
Jamie Lopez Bernal ◽  
Vanessa Saliba ◽  
...  
Keyword(s):  
Viral Load ◽  
Severe Acute Respiratory Syndrome ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Infectious Virus ◽  
Upper Respiratory Tract ◽  
Threshold Values ◽  
Rt Pcr ◽  
Cycle Threshold ◽  
Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

scholarly journals Shedding of infectious SARS-CoV-2 in symptomatic neonates, children and adolescents

2020 ◽  
Author(s):  
Arnaud G L’Huillier ◽  
G Torriani ◽  
F Pigny ◽  
L Kaiser ◽  
I Eckerle
Keyword(s):  
Respiratory Tract ◽  
Infectious Virus ◽  
Virus Isolation ◽  
Age Groups ◽  
Low Frequency ◽  
Nasopharyngeal Swab ◽  
Upper Respiratory Tract ◽  
Median Viral Load ◽  
Acute Respiratory Diseases ◽  
Upper Respiratory

AbstractChildren are underrepresented in COVID-19 case numbers, with most pediatric cases exhibiting limited severity, and do not seem to be major drivers of transmission, unlike for other respiratory viruses. That said, SARS-CoV-2 infects children across all age groups, and despite the high proportion of mild or asymptomatic infections, it would be naïve not to consider them as transmitters. To address this point we used cell culture to systematically assess the presence of cultivable SARS-CoV-2 in the upper respiratory tract in a cohort of our institution’s first 23 symptomatic neonates, children and teenagers with COVID-19 diagnosed by RT-PCR.Median age was 12.0 years (interquartile range [IQR 3.8–14.5], range 7 days-15.9 yrs). Most patients had an upper respiratory tract infection (n=13), followed by fever without source and pneumonia (each, n=2). Samples were collected at a median of 2 days (IQR 1–3) after symptom onset. Median viral load (VL) at time of diagnosis was 3.0×106 copies/ml (mean 4,4×108, IQR 6.9×103–4.4×108) from a nasopharyngeal swab (NPS).SARS-CoV-2 virus isolation was successful in 12/23 (52%) children after inoculating VeroE6 cells with a NPS specimen. SARS-CoV-2 isolation was determined by the presence of a typical cytopathic effect (CPE) and increased viral RNA in the supernatant. SARS-CoV-2 replication in all positive isolates (12/12) was confirmed by a second passage using new VeroE6 cells.Virus isolation was successful from NPS from all age groups, with a median initial VL of 1.7×108 copies/ml (mean 7.9×108, IQR 4.7×106–1.0×109) (Figure 1). The youngest patient that SARS-CoV-2 was isolated from was a 7-day old neonate. No correlation between disease presentation and success of virus isolation was observed.Our data show that initial VLs at diagnosis in symptomatic children is comparable to those in adults, and that symptomatic children of all ages shed infectious virus in early acute illness. Infectious virus isolation success was largely comparable to that of adults, although two specimens yielded an isolate at a lower VL (1.2×104 and 1.4×105 copies/ml) than what was observed in adults.SARS-CoV-2 shedding patterns of culture competent virus in symptomatic children resemble those observed in adults. Therefore, transmission of SARS-CoV-2 from children is plausible. Considering the relatively low frequency of infected children at this time, biological or other unknown factors could reduce transmission in this population. Both large serological investigations and systematic surveillance of acute respiratory diseases are needed to understand the role of children in this new pandemic.

scholarly journals The omicron (B.1.1.529) SARS-CoV-2 variant of concern does not readily infect Syrian hamsters

2021 ◽  
Author(s):  
Rana Abdelnabi ◽  
Caroline Shi-Yan Foo ◽  
Xin Zhang ◽  
Viktor Lemmens ◽  
Piet Maes ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Infectious Virus ◽  
Histopathological Examination ◽  
The Other ◽  
Viral Rna ◽  
Spike Protein ◽  
Upper Respiratory Tract ◽  
Syrian Hamsters ◽  
Bronchial Inflammation ◽  
Upper Respiratory

The emergence of SARS-CoV-2 variants of concern (VoCs) has exacerbated the COVID-19 pandemic. End of November 2021, a new SARS-CoV-2 variant namely the omicron (B.1.1.529) emerged. Since this omicron variant is heavily mutated in the spike protein, WHO classified this variant as the 5th variant of concern (VoC). We previously demonstrated that the other SARS-CoV-2 VoCs replicate efficiently in Syrian hamsters, alike also the ancestral strains. We here wanted to explore the infectivity of the omicron variant in comparison to the ancestral D614G strain. Strikingly, in hamsters that had been infected with the omicron variant, a 3 log10 lower viral RNA load was detected in the lungs as compared to animals infected with D614G and no infectious virus was detectable in this organ. Moreover, histopathological examination of the lungs from omicron-infecetd hamsters revealed no signs of peri-bronchial inflammation or bronchopneumonia. Further experiments are needed to determine whether the omicron VoC replicates possibly more efficiently in the upper respiratory tract of hamsters than in their lungs.

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