scholarly journals Sex and age bias viral burden and interferon responses during SARS-CoV-2 infection in ferrets

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magen E. Francis ◽  
Brian Richardson ◽  
Una Goncin ◽  
Mara McNeil ◽  
Melissa Rioux ◽  
...  

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and older ages. Here we investigated the impact of male sex and age comparing sex-matched or age-matched ferrets infected with SARS-CoV-2. Differences in temperature regulation was identified for male ferrets which was accompanied by prolonged viral replication in the upper respiratory tract after infection. Gene expression analysis of the nasal turbinates indicated that 1-year-old female ferrets had significant increases in interferon response genes post infection which were delayed in males. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.

2021 ◽  
Author(s):  
Magen E. Francis ◽  
Brian Richardson ◽  
Mara McNeil ◽  
Melissa Rioux ◽  
Mary K. Foley ◽  
...  

AbstractSARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) hospitalizations and deaths disportionally affect males and the elderly. Here we investigated the impact of male sex and age by infecting adult male, aged male, and adult female ferrets with SARS-CoV-2. Aged male ferrets had a decrease in temperature which was accompanied by prolonged viral replication with increased pathology in the upper respiratory tract after infection. Transcriptome analysis of the nasal turbinates and lungs indicated that female ferrets had significant increases in interferon response genes (OASL, MX1, ISG15, etc.) on day 2 post infection which was delayed in aged males. In addition, genes associated with taste and smell such as RTP1, CHGA, and CHGA1 at later time points were upregulated in males but not in females. These results provide insight into COVID-19 and suggests that older males may play a role in viral transmission due to decreased antiviral responses.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  

AbstractKey elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.


Author(s):  
Larissa May ◽  
Grant Tatro ◽  
Eduard Poltavskiy ◽  
Benjamin Mooso ◽  
Simson Hon ◽  
...  

Abstract Background Acute upper respiratory tract infections are a common cause of Emergency Department (ED) visits and often result in unnecessary antibiotic treatment.  Methods We conducted a randomized clinical trial to evaluate the impact of a rapid, multi-pathogen respiratory panel (RP) test versus usual care (control). Patients were eligible if they were ≥12 months old, had symptoms of upper respiratory infection or influenza like illness, and were not on antibiotics. The primary outcome was antibiotic prescription; secondary outcomes included antiviral prescription, disposition, and length of stay (ClinicalTrials.gov# NCT02957136). Results Of 191 patients enrolled, 93 (49%) received RP testing; 98 (51%) received usual care. Fifty-three (57%) RP and 7 (7%) control patients had a virus detected and reported during the ED visit (p=0.0001). Twenty (22%) RP patients and 33 (34%) usual care patients received antibiotics during the ED visit (-12% [95% CI -25%, 0.4%]; p=0.06/0.08); 9 RP patients received antibiotics despite having a virus detected. The magnitude of antibiotic reduction was greater in children (-19%) versus adults (-9%; post-hoc analysis). There was no difference in antiviral use, length of stay, or disposition. Conclusions Rapid RP testing was associated with a trend towards decreased antibiotic use, suggesting a potential benefit from more rapid viral tests in the ED. Future studies should determine if specific groups are more likely to benefit from testing and evaluate relative cost and effectiveness of broad testing, focused testing, and a combined diagnostic and antimicrobial stewardship approach.


Author(s):  
Jiawei Ma ◽  
Jiyuan Tu ◽  
Lin Tian ◽  
Goodarz Ahmadi

Abstract Elongated particles, such as asbestos and mineral fibers, are considered severe inhalation hazards due to their ability to penetrate into the deep lung. Frequently the dynamic behavior of the fibrous particles is attributed to their unique needle-like geometry. Therefore, understanding the interactions of the inhaled elongated particles with the airflow environment is of great significance. In this study, the transport and deposition of elongated micro-fibers in a realistic human nasal cavity is investigated numerically. The motion of the micro-fiber is resolved by solving the system of equations governing its coupled translational and rotational motions. The governing equations included the drag, the hydrodynamic torques that were evaluated using the Jeffrey model. The influence of the shear lift force was also included in these simulations. The no-slip wall boundary condition for airflow in the airways was used. Since the surface of airways is covered with mucus, when a fiber touches the surface, it was assumed to be deposited with no rebound. The study allows a close look at the non-spherical particle-flow dynamics with respect to the translation, rotation, coupling, and how the rotation affects the particle’s macroscopic transport and deposition properties. A series of simulations for different microfiber diameters and aspect ratios were performed. The simulation results are compared with the existing experimental data, and earlier computational model predictions and good agreements were obtained. The present study also seeks to provide additional insight into the transport processes of microfibers in the upper respiratory tract.


2016 ◽  
Vol 130 (9) ◽  
pp. 800-804 ◽  
Author(s):  
S Shemesh ◽  
S Tamir ◽  
A Goldfarb ◽  
T Ezri ◽  
Y Roth

AbstractBackground:Upper respiratory tract infection is the most common non-preventable cause of surgery cancellation. Consequently, surgeons and anaesthesiologists involved in elective ENT surgical procedures frequently face a dilemma of whether to proceed or to postpone surgery in affected children.Methods:A literature review was conducted and a practical assessment algorithm proposed.Conclusion:The risk–benefit assessment should take into consideration the impact of postponing the surgery intended to bring relief to the child and the risks of proceeding with general anaesthesia in an inflamed airway. The suggested algorithm for assessment may be a useful tool to support the decision of whether to proceed or to postpone surgery.


2021 ◽  
pp. 1-10
Author(s):  
I. Garaiova ◽  
Z. Paduchová ◽  
Z. Nagyová ◽  
D. Wang ◽  
D.R. Michael ◽  
...  

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.


2021 ◽  
Vol 9 ◽  
Author(s):  
Katarzyna Ślęzak ◽  
Łukasz Dembiński ◽  
Artur Konefał ◽  
Mikołaj Dąbrowski ◽  
Artur Mazur ◽  
...  

Antibiotic therapy must be carried out consistently and according to the guidelines. Viruses are the dominant cause of upper respiratory tract infections (URTIs) in children, as has been shown in many previous studies. Unnecessary antibiotic therapy should be avoided so that it does not affect patients' health and lead to the development of resistant bacterial strains. Here we report a national survey conducted in a group of 4,389 children to assess the impact of selected behavioral and environmental factors on antibiotic therapy in patients with URTIs. We found that selected environmental factors influenced the type of treatment. The place of residence, having siblings, an absence of vaccinations, the presence of allergies, and attendance at educational institutions were conducive to antibiotic therapy. These factors also influenced the frequency of hospitalization of children and their absence from nurseries, kindergartens, and schools, as well as the absence of their guardians from work.


2020 ◽  
pp. 59-65
Author(s):  
V. V. Shilenkova

Introduction. A biofilm is a community of bacteria embedded in a matrix consisting of polysaccharides, nucleic acids, and proteins. Biofilms are resistant to antibiotics, antiseptics, and immune defense factors of the human body. Currently, the role of bacterial biofilms in the pathogenesis of chronic infections is known. There are a lot of articles confirming the detection of biofilms in diseases of the upper respiratory tract and ear: adenoiditis, recurrent and chronic otitis, laryngitis.Biofilms and Chronic Rhinosinusitis (CRS). Biofilms can play a significant role in prolonging inflammation in the paranasal sinuses. Biofilms are found in 76.7% of patients with CRS. This fact can serve as one of the explanations for the refractoriness of drug therapy and recurrent inflammations after surgical treatment.Methods for Controlling Biofilms. Is there a Way Out? As part of the strategy of removing biofilm, it is important to destroy its structure to planktonic forms, which will allow for the process of managing CRS progress. Antibiotic therapy alone is considered insufficient. Nasal irrigation can provide a violation of the biofilm integrity due to the mechanical destruction of its matrix and have a significant impact on the outcome of the disease. The nasal irrigation preparation containing isotonic sea water solution added with carbon dioxide (CO2-0.4%) has such an effect. In an experimental study, it was shown that 98% of the bacteria were non-viable when processing Staphylococus aureus biofilm.Conclusion. The impact on biofilms should be complex, including medication, physical means, irrigation of the nasal cavity.


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