scholarly journals Sequential delivery of LAIV and SARS-CoV-2 in the ferret model can reduce SARS-CoV-2 shedding and does not result in enhanced lung pathology

2021 ◽  
Author(s):  
Kathryn A. Ryan ◽  
Katarzyna E. Schewe ◽  
Jonathan Crowe ◽  
Susan A. Fotheringham ◽  
Yper Hall ◽  
...  

AbstractCo-circulation of SARS-CoV-2 and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in co-infected patients. The lack of a readily available COVID-19 vaccine has reinforced the importance of influenza vaccine programmes during the COVID-19 pandemic. Live Attenuated Influenza Vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration might influence the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV (QLAIV) was administered to ferrets 3 days pre- or post-SARS-CoV-2 infection. LAIV administration did not exacerbate SARS-CoV-2 disease course or lung pathology with either regimen. Additionally, LAIV administered prior to SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract (URT). We conclude that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.

2013 ◽  
Vol 94 (8) ◽  
pp. 1791-1806 ◽  
Author(s):  
Chloe L. McIntyre ◽  
Nick J. Knowles ◽  
Peter Simmonds

Human rhinoviruses (HRVs) frequently cause mild upper respiratory tract infections and more severe disease manifestations such as bronchiolitis and asthma exacerbations. HRV is classified into three species within the genus Enterovirus of the family Picornaviridae. HRV species A and B contain 75 and 25 serotypes identified by cross-neutralization assays, although the use of such assays for routine HRV typing is hampered by the large number of serotypes, replacement of virus isolation by molecular methods in HRV diagnosis and the poor or absent replication of HRV species C in cell culture. To address these problems, we propose an alternative, genotypic classification of HRV-based genetic relatedness analogous to that used for enteroviruses. Nucleotide distances between 384 complete VP1 sequences of currently assigned HRV (sero)types identified divergence thresholds of 13, 12 and 13 % for species A, B and C, respectively, that divided inter- and intra-type comparisons. These were paralleled by 10, 9.5 and 10 % thresholds in the larger dataset of >3800 VP4 region sequences. Assignments based on VP1 sequences led to minor revisions of existing type designations (such as the reclassification of serotype pairs, e.g. A8/A95 and A29/A44, as single serotypes) and the designation of new HRV types A101–106, B101–103 and C34–C51. A protocol for assignment and numbering of new HRV types using VP1 sequences and the restriction of VP4 sequence comparisons to type identification and provisional type assignments is proposed. Genotypic assignment and identification of HRV types will be of considerable value in the future investigation of type-associated differences in disease outcomes, transmission and epidemiology.


2019 ◽  
Vol 9 (Supplement_1) ◽  
pp. S10-S14 ◽  
Author(s):  
Ian Shannon ◽  
Chantelle L White ◽  
Jennifer L Nayak

Abstract Live attenuated influenza vaccine (LAIV), or FluMist, was approved for use in the United States in 2003. This vaccine, administered intranasally, offers the advantage of stimulating immunity at the site of infection in the upper respiratory tract and, by mimicking natural infection, has the potential to elicit a multifaceted immune response. However, the development of immunity following LAIV administration requires viral replication, causing vaccine effectiveness to be impacted by both the replicative fitness of the attenuated viruses being administered and the degree of the host’s preexisting immunity. In this review, we discuss the current state of knowledge regarding the mechanisms of protection elicited by LAIV in children, contrast this with immune protection that develops upon vaccination with inactivated influenza vaccines, and briefly discuss both the potential advantages as well as challenges offered by this vaccination platform.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Gillian S. Slack ◽  
Phillip Brown ◽  
...  

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.


Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 163 ◽  
Author(s):  
Ishita Roy Chowdhury ◽  
Sai Yeddula ◽  
Shin-Hee Kim

Low pathogenic avian influenza (LPAI) viruses can silently circulate in poultry and wild aquatic birds and potentially mutate into highly pathogenic avian influenza (HPAI) viruses. In the U.S., recent emergence and spread of H7N8 and H7N9 HPAI viruses not only caused devastating losses to domestic poultry but also underscored the capability of LPAI viruses to mutate into HPAI viruses. Therefore, in this study, we evaluated pathogenicity and transmissibility of H7N8 and H7N9 LPAI viruses (the progenitors of HPAI viruses) in chickens and turkeys. We also included H7N2 isolated from an outbreak of LPAI in commercial chickens. H7 viruses replicated more efficiently in the respiratory tract than in the gastrointestinal tract, suggesting that their replication is restricted to the upper respiratory tract. Specifically, H7N2 replicated most efficiently in two-week-old chickens and turkeys. In contrast, H7N8 replicated least efficiently in those birds. Further, replication of H7N2 and H7N9 was restricted in the upper respiratory tract of four-week-old specific-pathogen-free (SPF) and broiler chickens. Despite their restricted replication, the two viruses efficiently transmitted from infected to naïve birds by direct contact, leading to seroconversion of contacted chickens. Our findings suggest the importance of continuous monitoring and surveillance of LPAI viruses in the fields.


Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 915
Author(s):  
Butler ◽  
Middleton ◽  
Haining ◽  
Layton ◽  
Rockman ◽  
...  

Circulating avian influenza viruses pose a significant threat, with human infections occurring infrequently but with potentially severe consequences. To examine the dynamics and locale of the adaptation process of avian influenza viruses when introduced to a mammalian host, we infected ferrets with H5N1 viruses. As expected, all ferrets infected with the human H5N1 isolate A/Vietnam/1203/2004 showed severe disease and virus replication outside the respiratory tract in multiple organs including the brain. In contrast infection of ferrets with the avian H5N1 virus A/Chicken/Laos/Xaythiani26/2006 showed a different collective pattern of infection; many ferrets developed and cleared a mild respiratory infection but a subset (25–50%), showed extended replication in the upper respiratory tract and developed infection in distal sites. Virus from these severely infected ferrets was commonly found in tissues that included liver and small intestine. In most instances the virus had acquired the common virulence substitution PB2 E627K but, in one case, a previously unidentified combination of two amino acid substitutions at PB2 S489P and NP V408I, which enhanced polymerase activity, was found. We noted that virus with high pathogenicity adaptations could be dominant in an extra-respiratory site without being equally represented in the nasal wash. Further ferret passage of these mutated viruses resulted in high pathogenicity in all ferrets. These findings illustrate the remarkable ability of avian influenza viruses that avoid clearance in the respiratory tract, to mutate towards a high pathogenicity phenotype during just a single passage in ferrets and also indicate a window of less than 5 days in which treatment may curtail systemic infection.


2016 ◽  
Vol 22 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Haider Abdul-Lateef Mousa

In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.


2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in upper respiratory tract leading to coronavirus disease 2019 (Covid-19). Severe Covid-19 is characterized by pulmonary pathologies associated with respiratory failure. Thus, therapeutics aimed at inhibiting entry of the virus or its internalization in the upper respiratory tract, are of interest. Herein, we report the prophylactic application of two intra-nasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and Til tailya in SARS-CoV2 infection hamster model. Prophylactic nasal instillation of these oil formulations exhibited reduced viral load in lungs, and resulted in reduced body weight loss and pneumonitis. In line with reduced viral load, histopathlogical analysis revealed a reduction in lung pathology in Anu oil group as compared to the control infected group. However, Til tailya group did not show a significant reduction in lung pathology. Furthermore, molecular analysis using mRNA expression profiling indicated reduced expression of pro-inflammatory cytokines genes, including Th1 and Th17 cytokines for both the intra-nasal formulations as a result of decreased viral load. Together, the prophylactic intra-nasal application of Annu oil seems to be useful in limiting both the viral load and disease severity disease in SARS-CoV2 infection in hamster model.


2018 ◽  
Vol 8 (2) ◽  
pp. 78-87
Author(s):  
Kamila Tuzim ◽  
Tomasz Tuzim ◽  
Magdalena Urbańczuk ◽  
Marcin Urbańczuk ◽  
Katarzyna Schab

According to the data of the World Health Organization, every year influenza develops in up to 1.575 billion people, and 1 million of them die. Although influenza viruses are the leading cause of the upper respiratory tract infections, severe neuromuscular complications occur as well, frequently leading to disability or even death. Children under five years of age and elderly people are at the highest risk of complications and mortality. The article discusses the selected neuromuscular complications of influenza, bringing particular attention to their etiology, symptomatology, diagnostics, and therapy.


Author(s):  
HAMID MERCHANT

While we wait for a confirmed drug or a vaccine for CoViD-19, it may be possible to intervene early to prevent the virus causing a severe disease to offer an alternative therapeutic strategy to control the pandemic. The global burden of CoViD-19 on the healthcare system can be significantly reduced by targeting CoViD-19 patients with or without symptoms who are self-isolating at home or in quarantine. If any therapeutic support can be offered to this group of patients that could attenuate the virus within the upper respiratory tract during the early stages of CoViD-19, it can give the body the time to produce enough antibodies to recover naturally from the disease before progressing into severe disease. An early intervention can, therefore, prevent the virus to get down the lower respiratory tract, reduce the number of cases with severe disease involving pneumonia and the need for hospitalisation. This article presents a simple yet holistic treatment strategy that involves inhaling steam supplemented with essential oils possessing wide spectrum antimicrobial properties in conjunction with oropharyngeal sanitisation to all those who are CoViD-19 positive or are under self-isolation due to symptoms. The approach is very simple, cheap, and effective in relieving the symptoms of the disease and is likely to reduce the viral load in the upper respiratory tract that may help recover from the infection. Since there is no vaccine or treatment yet approved to prevent or treat the CoViD-19, the importance of early intervention is invaluable in reducing the global disease burden. In the authors opinion, this strategy may be very effective to nip the infection in the bud before it gets difficult to treat and therefore, have a potential to significantly reduce the CoViD-19 associated hospitalisation.


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