Upper respiratory tract SARS-CoV-2 viral shedding in cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18776-e18776
Author(s):  
Zainab Shahid ◽  
Emily Baldrige ◽  
Sally Trufan ◽  
Courtney Schepel ◽  
Antoinette R. Tan ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Cancer Patients ◽  
Median Duration ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Viral Clearance ◽  
Upper Respiratory Tract ◽  
Viral Shedding ◽  
Upper Respiratory

e18776 Background: SARS-CoV-2 virus has been shown to persist in respiratory tract in immunocompromised patients. However, such data are lacking for both asymptomatic and symptomatic SARS-CoV-2 infection in cancer patients. We share our single center experience on duration of SARS-CoV-2 viral presence in the upper respiratory tract of cancer patients with SARS-CoV-2 infection (asymptomatic and symptomatic) detected by viral PCR. Methods: This is retrospective review of cancer patients with documented SARS-CoV-2 infection and measurement of viral shedding at Levine Cancer Institute. Testing indications were COVID-19 symptomatic illness, pre-procedural and pre-chemo testing. Prolonged shedding was defined as presence of viral RNA beyond 30 days after first positive test. To document viral clearance, patients required 2 negative SARS-CoV-2 PCR test separated by at least 24 hours and maximum 3 weeks apart either by nasopharyngeal or nasal PCR swab. Differences in distributions were identified between patients shedding virus more than 30 days and less than 30 days using uni- and multivariable logistic regression models. Statistical significance was set at p < 0.10 to enter the multivariable model, and p < 0.05 to remain. Results: Demographic data: median age 62 (range 20-93); 58.5% females; 70% White, 21% Black, and 7.4% Hispanics. Comorbidities included hypertension 43.2%, diabetes 16.7% and chronic lung disease 3.7%. Underlying malignancies were breast cancer 25%, hematologic cancer 22%, lung cancer 16% and genitourinary 11%. Chemotherapy was received by 26.5% patients within 4 weeks prior to testing. 162 patients were identified median duration of 18 days (range 4-90 days). Of these, 76% patients were tested for non-symptomatic indication with median duration of shedding 17 days (range 6-80) and 23% were tested for clinical symptoms with median duration of shedding 29 days (range 4-90) (p = < 0.001); 50% of patients never developed symptoms, whereas 35% patients with non-symptomatic testing indication, subsequently developed symptoms. Viral clearance by day 30, day 45, day 60 and day 90 was 78%, 93%, 97% and 100% respectively. Univariate analysis did not show difference between patients with prolonged shedding vs those shedding less than 30 days for age, gender, race, ethnicity, underlying malignancy, co-morbidities including body mass index, diabetes, chronic lung conditions, hypertension, or receipt of cytotoxic chemo. Multivariable analysis showed that presence of symptoms at any point during SARS-CoV-2 infection (OR 5.9, 95% CI 2.4-14.5, p < 0.001) was associated with prolonged shedding. Conclusions: Symptomatic SARS-CoV-2 infection is associated with prolonged viral shedding in cancer patients. Cancer patients can have asymptomatic SARS-CoV-2 infection. More studies are warranted to understand viral kinetics and its clinical implications in cancer patients.

Nasopharyngeal vs. adenoid cultures in children undergoing adenoidectomy: prevalence of bacterial pathogens, their interactions and risk factors

2014 ◽  
Vol 143 (4) ◽  
pp. 821-830 ◽  
Author(s):  
I. KORONA-GLOWNIAK ◽  
A. NIEDZIELSKI ◽  
U. KOSIKOWSKA ◽  
A. GRZEGORCZYK ◽  
A. MALM
Keyword(s):  
Risk Factors ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Bacterial Colonization ◽  
Statistical Significance ◽  
Positive Association ◽  
Upper Respiratory Tract Infections ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Tract Infections

SUMMARYStreptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus colonization of the adenoids and nasopharynx in 103 preschool children who underwent adenoidectomy for recurrent upper respiratory tract infections was examined. Bacterial interactions and risk factors for bacterial colonization of the nasopharynx and adenoids, separately, were analysed statistically. The prevalence of simultaneous isolation from both anatomical sites was 45·6% for S. pneumoniae, 29·1% for H. influenzae, 15·5% for M. catarrhalis and 18·4% for S. aureus. Three pathogens were significantly more frequent together from adenoid samples; nasopharyngeal swabs more often yielded a single organism, but without statistical significance. M. catarrhalis and S. aureus significantly more frequently co-existed with S. pneumoniae and H. influenzae than with each other and a positive association of S. pneumoniae and H. influenzae in adenoid samples was evident. Several differences between risk factors for nasopharyngeal and adenoid colonization by the individual pathogens were observed. We conclude that the adenoids and nasopharynx appear to differ substantially in colonization by pathogenic microbes but occurrence of H. influenzae and S. pneumoniae in the nasopharynx could be predictive of upper respiratory tract infections.

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 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 Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

2020 ◽  
Author(s):  
Pamela C. Proud ◽  
Daphne Tsitoura ◽  
Robert J. Watson ◽  
Brendon Y Chua ◽  
Marilyn J. Aram ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Viruses ◽  
Nasal Administration ◽  
Infection Model ◽  
Upper Respiratory Tract ◽  
Viral Shedding ◽  
Lower Respiratory Tract Disease ◽  
Rapid Spread ◽  
Upper Respiratory ◽  
Tract Disease

AbstractRespiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission.We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19.

scholarly journals Prophylactic intranasal administration of a TLR2/6 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

EBioMedicine ◽  
2021 ◽  
Vol 63 ◽  
pp. 103153
Author(s):  
Pamela C. Proud ◽  
Daphne Tsitoura ◽  
Robert J. Watson ◽  
Brendon Y. Chua ◽  
Marilyn J. Aram ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Intranasal Administration ◽  
Upper Respiratory Tract ◽  
Viral Shedding ◽  
Upper Respiratory

scholarly journals Mutations in haemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility

2013 ◽  
Vol 94 (6) ◽  
pp. 1220-1229 ◽  
Author(s):  
Holly Shelton ◽  
Kim L. Roberts ◽  
Eleonora Molesti ◽  
Nigel Temperton ◽  
Wendy S. Barclay
Keyword(s):  
Respiratory Tract ◽  
Influenza A ◽  
Vaccine Virus ◽  
Ph Stability ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Viral Shedding ◽  
H5n1 Influenza ◽  
Upper Respiratory ◽  
Pandemic Strains

The H5N1 influenza A viruses have circulated widely in the avian population for 10 years with only sporadic infection of humans observed and no sustained human to human transmission. Vaccination against potential pandemic strains is one strategy in planning for future influenza pandemics; however, the success of live attenuated vaccines for H5N1 has been limited, due to poor replication in the human upper respiratory tract (URT). Mutations that increase the ability of H5N1 viruses to replicate in the URT will aid immunogenicity of these vaccines and provide information about humanizing adaptations in H5N1 strains that may signal transmissibility. As well as mediating receptor interactions, the haemagglutinin (HA) protein of influenza facilitates fusion of the viral membrane and genome entry into the host cell; this process is pH dependent. We have shown in this study that the pH at which a panel of avian influenza HA proteins, including H5, mediate fusion is higher than that for human influenza HA proteins, and that mutations in the H5 HA can reduce the pH of fusion. Coupled with receptor switching mutations, increasing the pH stability of the H5 HA resulted in increased viral shedding of H5N1 from the nasal cavity of ferrets and contact transmission to a co-housed animal. Ferret serum antibodies induced by infection with any of the mutated H5 HA viruses neutralized HA pseudotyped lentiviruses bearing homologous or heterologous H5 HAs, suggesting that this strategy to increase nasal replication of a vaccine virus would not compromise vaccine efficacy.

scholarly journals Assessment of the efficacy of SARS-CoV-2 vaccines in non-human primate studies: a systematic review

2022 ◽  
Vol 2 ◽  
pp. 4
Author(s):  
Michel Jacques Counotte ◽  
Mariana Avelino de Souza Santos ◽  
Koert J Stittelaar ◽  
Wim H M van der Poel ◽  
Jose L Gonzales
Keyword(s):  
Respiratory Tract ◽  
Severe Disease ◽  
Population Level ◽  
Diagnostic Methods ◽  
Viral Rna ◽  
Upper Respiratory Tract ◽  
Viral Shedding ◽  
Proxy Measure ◽  
Preclinical Trials ◽  
Upper Respiratory

Background: The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the rapid and successful development of vaccines to help mitigate the effect of COVID-19 and circulation of the virus. Vaccine efficacy is often defined as capacity of vaccines to prevent (severe) disease. However, the efficacy to prevent transmission or infectiousness is equally important at a population level. This is not routinely assessed in clinical trials. Preclinical vaccine trials provide a wealth of information about the presence and persistence of viruses in different anatomical sites. Methods: We systematically reviewed all available preclinical SARS-CoV-2 candidate vaccine studies where non-human primates were challenged after vaccination (PROSPERO registration: CRD42021231199). We extracted the underlying data, and recalculated the reduction in viral shedding. We summarized the efficacy of  vaccines to reduce viral RNA shedding after challenge by standardizing and stratifying the results by different anatomical sites and diagnostic methods. We considered shedding of viral RNA as a proxy measure for infectiousness. Results: We found a marked heterogeneity between the studies in the experimental design and the assessment of the outcomes. The best performing vaccine candidate per study caused only low (6 out of 12 studies), or moderate (5 out of 12) reduction of viral genomic RNA, and low (5 out of 11 studies) or moderate (3 out of 11 studies) reduction of subgenomic RNA in the upper respiratory tract, as assessed with nasal samples. Conclusions: Since most of the tested vaccines only triggered a low or moderate reduction of viral RNA in the upper respiratory tract, we need to consider that most SARS-CoV-2 vaccines that protect against disease might not fully protect against infectiousness and vaccinated individuals might still contribute to SARS-CoV-2 transmission. Careful assessment of secondary attack rates from vaccinated individuals is warranted. Standardization in design and reporting of preclinical trials is necessary.

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