scholarly journals Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 113
Author(s):  
Helen E. Everett ◽  
Fabian Z. X. Lean ◽  
Alexander M. P. Byrne ◽  
Pauline M. van Diemen ◽  
Shelley Rhodes ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Humoral Response ◽  
Asymptomatic Infection ◽  
Human Infection ◽  
Viral Rna ◽  
Post Inoculation ◽  
Upper Respiratory Tract ◽  
Infection Dynamics ◽  
Genomic Sequence Analysis ◽  
Upper Respiratory

Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.

scholarly journals Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Gillian S. Slack ◽  
Phillip Brown ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Viral Rna ◽  
Dose Titration ◽  
High Dose ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Virus Shedding ◽  
Upper Respiratory ◽  
Dose Dependent ◽  
Titration Study

AbstractThere is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

scholarly journals An outbreak of SARS-CoV-2 with high mortality in mink (Neovison vison) on multiple Utah farms

2021 ◽  
Author(s):  
Chrissy Eckstrand ◽  
Tom Baldwin ◽  
Mia Kim Torchetti ◽  
Mary Lea Killian ◽  
Kerry A Rood ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Clinical Signs ◽  
Viral Transmission ◽  
Viral Rna ◽  
Upper Respiratory Tract ◽  
Tracheobronchial Lymph Node ◽  
Multiple Organs ◽  
Upper Respiratory ◽  
Polymerase Chain

The breadth of animal hosts that are susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may serve as reservoirs for continued viral transmission are not known entirely. In August 2020, an outbreak of SARS-CoV-2 occurred in multiple mink farms in Utah and was associated with high mink mortality and rapid viral transmission between animals. The outbreak's epidemiology, pathology, molecular characterization, and tissue distribution of virus within infected mink is provided. Infection of mink was likely by reverse zoonosis. Once established, infection spread rapidly between independently housed animals and farms, and caused severe respiratory disease and death. Clinical signs were most notably sudden death, anorexia, and increased respiratory effort. Gross pathology examination revealed severe pulmonary congestion and edema. Microscopically there was pulmonary edema with moderate vasculitis, perivasculitis, and fibrinous interstitial pneumonia. Reverse transcriptase polymerase chain reaction (RT-PCR) of tissues collected at necropsy demonstrated the presence of SARS-CoV-2 viral RNA in multiple organs including nasal turbinates, lung, tracheobronchial lymph node, epithelial surfaces, and others. Whole genome sequencing from multiple mink was consistent with published SARS-CoV-2 genomes with few polymorphisms. The Utah mink SARS-CoV-2 strain fell into Clade GH, which is unique among mink and other animal strains sequenced to date and did not share other spike RBD mutations Y453F and F486L found in mink. Localization of viral RNA by in situ hybridization revealed a more localized infection, particularly of the upper respiratory tract. Mink in the outbreak reported herein had high levels of virus in the upper respiratory tract associated with mink-to-mink transmission in a confined housing environment and were particularly susceptible to disease and death due to SARS-CoV-2 infection.

FEATURES OF RESIDUAL PHENOMENA AND CONSEQUENCES OF COVID-19 (REVIEW)

Vestnik ◽  
2021 ◽  
pp. 335-340
Author(s):  
Г.Н. Абуова ◽  
Г.А. Айтмуратова ◽  
Т.В. Полукчи ◽  
Ф.А. Бердалиева ◽  
Г.Г. Шаймерденова
Keyword(s):  
Asymptomatic Infection ◽  
Multiple Organ ◽  
Upper Respiratory Tract ◽  
Respiratory Tract Disease ◽  
Infected People ◽  
Life Threatening ◽  
Upper Respiratory ◽  
Tract Disease ◽  
Timely Treatment

Проведен литературный обзор об особенностях остаточных явлений и последствий COVID-19 на основе данных, опубликованных до настоящего времени. К началу января 2021 года COVID-19, сопровождающийся тяжелым острым респираторным синдромом, вызванным коронавирусом (SARS-CoV-2), привел к более чем 83 миллионам подтвержденных случаев и более чем 1,8 миллионам смертей. Клинический спектр инфекции SARS-CoV-2 широк, включая бессимптомную инфекцию, лихорадку, усталость, миалгии, легкое заболевание верхних дыхательных путей, тяжелую и опасную для жизни вирусную пневмонию, требующую госпитализации и летальный исход. COVID-19 - это новое заболевание, и остается неопределенность в отношении возможных долгосрочных последствий для здоровья. На сегодняшний день известно, что у большинства инфицированных, особенно в молодом возрасте, заболевание имеет легкое течение, по сравнению с лицами старшего возраста. У некоторых пациентов заболевание быстро прогрессирует и развиваются различные осложнения, в т.ч. полиорганная недостаточность. Поэтому раннее выявление и своевременное лечение критических случаев имеет решающее значение. A literature review on the features of residual phenomena and consequences of COVID-19 is analyzed on the basis of data published so far. By the beginning of January 2021, COVID-19, accompanied by severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2), led to more than 83 million confirmed cases and more than 1.8 million deaths. The clinical spectrum of SARS-CoV-2 infection is wide, including asymptomatic infection, fever, fatigue, myalgia, mild upper respiratory tract disease, severe and life-threatening viral pneumonia requiring hospitalization, and death. COVID-19 is a new disease, and uncertainty remains about possible long-term health consequences. To date, it is known that the majority of infected people, especially at a young age, have a mild course of the disease, compared with older people. In some patients, the disease progresses rapidly and various complications develop, including multiple organ failure. Therefore, early detection and timely treatment of critical cases is crucial.

scholarly journals Immunization with Live Neisseria lactamica Protects Mice against Meningococcal Challenge and Can Elicit Serum Bactericidal Antibodies

2006 ◽  
Vol 74 (11) ◽  
pp. 6348-6355 ◽  
Author(s):  
Yanwen Li ◽  
Qian Zhang ◽  
Megan Winterbotham ◽  
Eva Mowe ◽  
Andrew Gorringe ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Protective Immunity ◽  
Human Infection ◽  
Natural Immunity ◽  
Upper Respiratory Tract ◽  
Nasopharyngeal Colonization ◽  
Neisseria Lactamica ◽  
Upper Respiratory ◽  
Disease Understanding ◽  
Infants And Young Children

ABSTRACT Natural immunity against Neisseria meningitidis is thought to develop following nasopharyngeal colonization with this bacterium or other microbes expressing cross-reactive antigens. Neisseria lactamica is a commensal of the upper respiratory tract which is often carried by infants and young children; epidemiological evidence indicates that colonization with this bacterium can elicit serum bactericidal activity (SBA) against Neisseria meningitidis, the most validated correlate of protective immunity. Here we demonstrate experimentally that immunization of mice with live N. lactamica protects animals against lethal meningococcal challenge and that some, but not all, strains of N. lactamica elicit detectable SBA in immunized animals regardless of the serogroup of N. meningitidis. While it is unlikely that immunization with live N. lactamica will be implemented as a vaccine against meningococcal disease, understanding the basis for the induction of cross-protective immunity and SBA should be valuable in the design of subunit vaccines for the prevention of this important human infection.

scholarly journals Human Infection withFusobacterium necrophorumwithout Jugular Venous Thrombosis: A Varied Presentation of Lemierre’s Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Muhammad Asim Rana ◽  
Yashwant Kumar ◽  
Abdullah Ali Lashari ◽  
Ahmed F. Mady
Keyword(s):  
Nerve Palsy ◽  
Jugular Vein ◽  
Kidney Injury ◽  
Severe Pneumonia ◽  
Fusobacterium Necrophorum ◽  
Human Infection ◽  
Upper Respiratory Tract ◽  
Lemierre’S Syndrome ◽  
Upper Respiratory ◽  
Lemierre's Syndrome

Lemierre’s syndrome is also known as postangina septicemia, which is commonly caused byFusobacterium necrophorumalso known as Necrobacillus and also by other microorganisms likeStaphylococcus,Streptococcus,Peptostreptococcus, andBacteroides. Though the disease starts as an upper respiratory tract infection, it may spread and cause thrombophlebitis of the internal jugular vein. It may present itself through cranial nerve palsy or sepsis involving distant organs like the lungs or bones. It is also known as forgotten disease because of its rarity.Fusobacterium necrophorumusually causes infection in animals and rarely affects humans. We hereby present a case of Necrobacillus infection which did not cause any thrombophlebitis but resulted in severe pneumonia and acute kidney injury, leading to respiratory failure and requiring mechanical ventilation.

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 G. Diel
Keyword(s):  
Respiratory Tract ◽  
Viral Replication ◽  
Viral Entry ◽  
Upper Respiratory Tract ◽  
Infectious Dose ◽  
Virus Shedding ◽  
Age Related ◽  
Infection Dynamics ◽  
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 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 a differential expression have been described in young and old people, with a higher level of expressing cells being detected in the nasal brushing of older people when compared to 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 when compared to young animals and the viral replication in the URT and shedding is 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.

scholarly journals SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness: a living systematic review and meta-analysis

2020 ◽  
Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Symptom Onset ◽  
Grey Literature ◽  
Viral Rna ◽  
Viral Dynamics ◽  
Upper Respiratory Tract ◽  
Live Virus ◽  
Viral Shedding ◽  
Upper Respiratory

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.

scholarly journals Undetectable SARS-CoV-2 in a nasopharyngeal swab but persistent viral RNA from deep lung swabs: findings from an autopsy

2020 ◽  
Vol 13 (10) ◽  
pp. e237446
Author(s):  
Prema Seetulsingh ◽  
Chiranthi Iresha Kannangara ◽  
Paul Richman
Keyword(s):  
Accurate Diagnosis ◽  
Viral Rna ◽  
Nasopharyngeal Swab ◽  
Upper Respiratory Tract ◽  
Shortness Of Breath ◽  
Radiological Findings ◽  
Global Pandemic ◽  
Nasal Swabs ◽  
Upper Respiratory ◽  
Preventative Interventions

During the global pandemic of COVID-19 accurate diagnosis of the infection by demonstrating SARS-CoV-2 viral RNA by PCR in specimens is crucial for therapeutic and preventative interventions. There have been instances where nasal and throat swabs have been negative despite the patient having typical clinical and radiological findings compatible with the disease. We report a case of a man in his late 50s, brought to the hospital following a cardiac arrest and prolonged unsuccessful resuscitation. The history was typical for COVID-19 with fever for 10 days and worsening shortness of breath. His throat and nasal swabs (after death) were negative for SARS-CoV-2. A limited diagnostic autopsy was performed after 27 days, and lung swabs confirmed presence of SARS-CoV-2. This case highlights the importance of lung swabs when initial upper respiratory tract swabs are negative and proves that the virus can be detected from dead human tissue almost a month later.

scholarly journals Group C streptococci in human infection: a study of 308 isolates with clinical correlations

1989 ◽  
Vol 102 (3) ◽  
pp. 379-390 ◽  
Author(s):  
M. Barnham ◽  
J. Kerby ◽  
R. S. Chandler ◽  
M. R. Millar
Keyword(s):  
Septic Arthritis ◽  
Pleural Empyema ◽  
Human Infection ◽  
Upper Respiratory Tract ◽  
Erythromycin Resistance ◽  
Acute Epiglottitis ◽  
Abdominal Abscesses ◽  
Clinical Correlations ◽  
Upper Respiratory ◽  
Lancefield Group

SUMMARYA collection of 308 clinical isolates of β-haemolytic Lancefield group C streptococci was assembled from laboratories in England. Nigeria and New Zealand. Of these, 276 isolates wereStreptococcus equisimilis. 23S. milleriand nineS. zooepidemicus. Isolates ofS. equisimilisin the African collection, though few, gave higher rates of lactose and raffinose fermentation, aesculin hydrolysis and positive α-galactosidase reactions than those from elsewhere. Erythromycin resistance was found in 1·9% of the English isolates ofS. equisimilis.Strains from superficial infections accounted for 88 % of the collection and were most commonly isolated from the upper respiratory tract, skin or wounds. Amongst the 36 patients yielding isolates from deep sitesS. equisimiliswas found in septicaemia, cellulitis, abscess, peritonitis, septic arthritis, pneumonia, mycotic aneurysm and acute epiglottitis.S. milleriwas found in abdominal abscesses, peritonitis, pleural empyema and osteomyelitis andS. zooepidemicuswas found in septicaemia, pneumonia, meningitis and septic arthritis. Within the collection an unselected general catchment of 214 isolates of group C streptococci from the laboratories in Yorkshire showed the following species: from 199 superficial infections 94%S. equisimilis. 5%S. milleriand 1%S. zooepidemicusand 15 patients with deeper, more agressive infections 67, 27 and 6·7% of these species respectively.

scholarly journals The Contrasting Role of Nasopharyngeal Angiotensin Converting Enzyme 2 (ACE2) Expression in SARS-CoV-2 Infection: A Cross-Sectional Study of People Tested for COVID-19 in British Columbia

2020 ◽  
Author(s):  
Aidan M. Nikiforuk ◽  
Kevin S. Kuchinski ◽  
David D.W. Twa ◽  
Christine D. Lukac ◽  
Hind Sbihi ◽  
...  
Keyword(s):  
British Columbia ◽  
Cross Sectional Study ◽  
Viral Rna ◽  
Bivariate Analysis ◽  
Upper Respiratory Tract ◽  
Cross Sectional ◽  
Angiotensin Converting Enzyme 2 ◽  
Biological Sex ◽  
Upper Respiratory

SummaryBackgroundAngiotensin converting enzyme 2 (ACE2) serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 expression in people tested for COVID-19 and the relationship between ACE2 expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 (TMPRSS2), soluble ACE2, age, and biological sex.MethodsA cross-sectional study of n=424 participants aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Participants who tested negative or positive for COVID-19 were matched by age and biological sex. Viral and host gene expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts.FindingsAnalysis shows no association between age and nasopharyngeal ACE2 expression in those who tested negative for COVID-19 (P=0·092). Mean expression of transmembrane (P=1·2e-4), soluble ACE2 (P<0·0001) and TMPRSS2 (P<0·0001) differed between COVID-19-negative and -positive groups. In bivariate analysis of COVID-19-positive participants, expression of transmembrane ACE2 positively correlated with SARS-CoV-2 RNA viral load (P<0·0001), expression of soluble ACE2 negatively correlated (P<0·0001), and no correlation was found with TMPRSS2 (P=0·694). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 expression (B=0·886, 95%CI:[0·596 to 1·18]), while expression of soluble ACE2 may protect against high viral RNA load in the upper respiratory tract (B= −0·0990, 95%CI:[−0·176 to −0·0224]).InterpretationNasopharyngeal ACE2 expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transmembrane ACE2 positively correlates, while soluble ACE2 negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2.FundingThis project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Sign in / Sign up

Export Citation Format

Share Document