scholarly journals Effect of prophylactic use of intra-nasal oil formulations in the hamster model of Covid-19

2021 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory ◽  
Prophylactic Use

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.

scholarly journals Effect of Prophylactic Use of Intranasal Oil Formulations in the Hamster Model of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaigham Abbas Rizvi ◽  
Manas Ranjan Tripathy ◽  
Nishant Sharma ◽  
Sandeep Goswami ◽  
N Srikanth ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Viral Entry ◽  
Body Weight Loss ◽  
Histopathological Analysis ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Reduced Body ◽  
Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection initiates with viral entry in the 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 the entry of the virus or its internalization in the upper respiratory tract are of interest. Herein, we report the prophylactic application of two intranasal formulations provided by the National Medicinal Plant Board (NMPB), Anu oil and til tailya, in the hamster model of SARS-CoV-2 infection. Prophylactic intra-nasal instillation of these oil formulations exhibited reduced viral load in lungs and resulted in reduced body weight loss and lung-pneumonitis. In line with reduced viral load, histopathological analysis revealed a reduction in lung pathology in the Anu oil group as compared to the control infected group. However, the 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 cytokine genes, including Th1 and Th17 cytokines for both the intranasal formulations as a result of decreased viral load. Together, the prophylactic intranasal application of Anu oil seems to be useful in limiting both viral load and severity in SARS-CoV2 infection in the hamster model.

scholarly journals Comparison of the pathogenicity and virus shedding of SARS CoV-2 VOC 202012/01 and D614G variant in hamster model

2021 ◽  
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya D Yadav ◽  
Dimpal Nyayanit ◽  
Gururaj Deshpande ◽  
Anita Shete-Aich ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Body Weight Loss ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Hamster Model ◽  
Virus Shedding ◽  
Vaccination Programs

AbstractThe emergence of SARS-CoV-2 variants has posed a serious challenge to public health system and vaccination programs across the globe. We have studied the pathogenicity and virus shedding pattern of the SARS-CoV-2 VOC 202012/01 and compared with D614G variant in Syrian hamsters. VOC 202012/01 could produce disease in hamsters characterized by body weight loss and respiratory tract tropism but mild lung pathology. Further, we also documented that neutralizing antibodies developed against VOC 202012/01 could equally neutralize D614G variant. Higher load of VOC 202012/01 in the nasal wash specimens was observed during the first week of infection outcompeting the D614G variant. The findings suggest increased fitness of VOC 202012/01 to the upper respiratory tract which could lead to higher transmission. Further investigations are needed to understand the transmissibility of new variants.One-Sentence SummarySARS-CoV-2 VOC 202012/01 infected hamsters demonstrated high viral RNA shedding through the nasal secretions and significant body weight loss with mild lung pathology compared to the D614G variant.

scholarly journals Factors associated with the risk of upper respiratory tract bacterial infections among HIV-positive patients

2020 ◽  
Author(s):  
Agata Skrzat-Klapaczynska ◽  
Marcin Paciorek ◽  
Ewa Firlag-Burkacka ◽  
Andrzej Horban ◽  
Justyna Dominika Kowalska
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Bacterial Infections ◽  
Cd4 Count ◽  
Hiv Positive ◽  
Upper Respiratory Tract ◽  
Detectable Viral Load ◽  
Factors Associated ◽  
Multivariate Survival ◽  
Upper Respiratory

Background The risk and characteristics of upper respiratory tract (URT) bacterial infections (URT-BI) among HIV (+) patients is understudied. We analyzed factors associated with its occurrence and the spectrum of pathogens among patients routinely followed at the HIV Out-Patient Clinic in Warsaw. Methods All symptomatic HIV (+) patients with available URT swab culture were included into analyses. Patients were followed from the day of registration in the clinic until first positive URT swab culture or last clinical visit. Cox proportional hazard models were used to identify factors associated with positive URT swabs culture (those with p<0.1 in univariate included into multivariable). Results In total 474 patients were included into the analyses, 166 with positive URT swab. In general 416 (87.8%) patients were male, 342 (72.1%) were infected through MSM contact, 253 (53.4%) were on antiretroviral therapy. Median follow-up time was 3.4 (1.3-5.7) years, age 35.2 (30.6-42.6) years and CD4+ count 528 (400-685) cells/μl. The most common pathogens were S. aureus (40.4%) and S. pyogenes (13.9%) (Table 1). Patients with URT-BI were more likely to be MSM (68.5% vs 78.9%; p<0.016), have detectable viral load (20.9% vs 12.0%; p<0.0001) and CD4+ cell count <500 cells/μl (55.2% vs 39.0%; p=0.003) (Table 2). In multivariate survival analyses detectable viral load (HR3.13; 95%Cl: 2.34-4.19) and MSM (1.63;1.09-2.42) were increasing, but older age (0.63;0.58-0.69, per 5 years older) and higher CD4+ count (0.90;0.85-0.95, per 100 cells/μl) decreasing the risk of URT-BI (Table 2). Conclusions URT BI are common among HIV (+) positive patients with high CD4+ count. Similarly to general population most common patogens are S. aureus and S. pyogenes. Risk factors identified in multivariate survival analysis indicate that younger MSM patients with detectable HIV viral load are at highest risk. In clinical practice this group of patients requires special attention.

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 Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Critical Factor ◽  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Viral Loads ◽  
Antiviral Responses ◽  
Upper Respiratory

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.

scholarly journals Paired nasopharyngeal and deep lung testing for SARS-CoV2 reveals a viral gradient in critically ill patients: a multi-centre study

2020 ◽  
Author(s):  
Islam Hamed ◽  
Nesreen Shaban ◽  
Marwan Nassar ◽  
Sam Love ◽  
Martin D Curran ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Lower Respiratory Tract ◽  
Limit Of Detection ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Multi Centre Study ◽  
Upper Respiratory

Introduction Samples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load. Objectives The objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients. Methods SARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated. Results Results collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO). Conclusions It has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.

scholarly journals Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

2017 ◽  
Vol 64 (suppl_3) ◽  
pp. S337-S346 ◽  
Author(s):  
Daniel R. Feikin ◽  
Wei Fu ◽  
Daniel E. Park ◽  
Qiyuan Shi ◽  
Melissa M. Higdon ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Severe Pneumonia ◽  
Upper Respiratory Tract ◽  
Upper Respiratory

scholarly journals A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients

2019 ◽  
Vol 71 (11) ◽  
pp. 2777-2786 ◽  
Author(s):  
Roy F Chemaly ◽  
Sanjeet S Dadwal ◽  
Anne Bergeron ◽  
Per Ljungman ◽  
Yae-Jean Kim ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Weighted Average ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Hematopoietic Cell Transplant ◽  
Double Blind ◽  
Time Weighted Average ◽  
Upper Respiratory ◽  
Syncytial Virus

Abstract Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (&lt;200/µL) and ribavirin use; were randomized, stratified by lymphopenia (&lt;200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36.

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