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.

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 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.

scholarly journals CoViD-19: An early intervention therapeutic strategy to prevent developing a severe disease as an alternative approach to control the pandemic

2020 ◽  
Author(s):  
HAMID MERCHANT
Keyword(s):  
Early Intervention ◽  
Respiratory Tract ◽  
Therapeutic Strategy ◽  
Wide Spectrum ◽  
Severe Disease ◽  
Antimicrobial Properties ◽  
The Body ◽  
Upper Respiratory Tract ◽  
Holistic Treatment ◽  
Upper Respiratory

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.

scholarly journals Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

2015 ◽  
Vol 90 (4) ◽  
pp. 1888-1897 ◽  
Author(s):  
Kathryn M. Edenborough ◽  
Suzanne Lowther ◽  
Karen Laurie ◽  
Manabu Yamada ◽  
Fenella Long ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Severe Disease ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza Virus ◽  
Viral Spread ◽  
H5n1 Influenza ◽  
Upper Respiratory ◽  
The Brain

ABSTRACTAlthough avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease.IMPORTANCERisks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection.

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 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 Upper Respiratory Tract Diseases in Athletes in Different Sports Disciplines

2016 ◽  
Vol 53 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Anna Gałązka-Franta ◽  
Edyta Jura-Szołtys ◽  
Wojciech Smółka ◽  
Radosław Gawlik
Keyword(s):  
Respiratory Tract ◽  
Allergic Diseases ◽  
Medical Problem ◽  
Diagnostic Methods ◽  
Respiratory Tract Diseases ◽  
Upper Respiratory Tract ◽  
High Prevalence ◽  
Upper Respiratory ◽  
Tract Disease ◽  
Tract Infections

AbstractUpper respiratory tract diseases in athletes are a very common medical problem. Training conditions in different sports disciplines increase the risk of upper respiratory disease. Epidemiological evidence suggests that heavy acute or chronic exercise is related to an increased incidence of upper respiratory tract infections in athletes. Regular physical exercise at high intensity may lead to transient immunosuppression due to high prevalence of allergic diseases in athletes. Regardless of the cause they can exclude athletes from the training program and significantly impair their performance. In the present work, the most common upper respiratory tract diseases in athletes taking into account the disciplines in which they most often occur were presented. The focus was laid on symptoms, diagnostic methods and pharmacotherapy. Moreover, preventive procedures which can help reduce the occurrence of upper respiratory tract disease in athletes were presented. Management according to anti-doping rules, criteria for return to training and competition as an important issues of athlete’s health were discussed.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document