scholarly journals The omicron (B.1.1.529) SARS-CoV-2 variant of concern does not readily infect Syrian hamsters

2021 ◽  
Author(s):  
Rana Abdelnabi ◽  
Caroline Shi-Yan Foo ◽  
Xin Zhang ◽  
Viktor Lemmens ◽  
Piet Maes ◽  
...  

The emergence of SARS-CoV-2 variants of concern (VoCs) has exacerbated the COVID-19 pandemic. End of November 2021, a new SARS-CoV-2 variant namely the omicron (B.1.1.529) emerged. Since this omicron variant is heavily mutated in the spike protein, WHO classified this variant as the 5th variant of concern (VoC). We previously demonstrated that the other SARS-CoV-2 VoCs replicate efficiently in Syrian hamsters, alike also the ancestral strains. We here wanted to explore the infectivity of the omicron variant in comparison to the ancestral D614G strain. Strikingly, in hamsters that had been infected with the omicron variant, a 3 log10 lower viral RNA load was detected in the lungs as compared to animals infected with D614G and no infectious virus was detectable in this organ. Moreover, histopathological examination of the lungs from omicron-infecetd hamsters revealed no signs of peri-bronchial inflammation or bronchopneumonia. Further experiments are needed to determine whether the omicron VoC replicates possibly more efficiently in the upper respiratory tract of hamsters than in their lungs.

2021 ◽  
Author(s):  
Chrissy Eckstrand ◽  
Tom Baldwin ◽  
Mia Kim Torchetti ◽  
Mary Lea Killian ◽  
Kerry A Rood ◽  
...  

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.


1934 ◽  
Vol 34 (2) ◽  
pp. 195-202 ◽  
Author(s):  
L. Hoyle

In previous studies of the bacterial flora of the upper respiratory tract and its variations during attacks of acute coryza (Hoyle, 1932), it was found that there was in many cases a striking relationship between the appearance of certain organisms with definite pathogenic properties towards the lower animals, in the upper respiratory tract, and the occurrence of acute infections. This relationship was especially marked in the case of the influenza bacillus, and it was suggested that this organism played a prominent part in the aetiology of upper respiratory infections. The significance of the influenza bacillus in acute coryza has been noted by various workers (Noble, Fisher and Brainard, 1928; Burky and Smillie, 1929; Webster and Clow, 1932; Kneeland and Dawes, 1932), but on the other hand various observers have found the incidence of influenza bacilli in the respiratory tract to be the same in normal health and in acute coryza, and Fleming (1929) and Fleming and Maclean (1930) have devised a technique by means of which they claim to have isolated influenza bacilli in 100 per cent, of normal throats. One possible explanation of these conflicting results may be found in the absence of any very exact criterion of what constitutes a typical influenza bacillus.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huibi Cao ◽  
Juntao Mai ◽  
Zhichang Zhou ◽  
Zhijie Li ◽  
Rongqi Duan ◽  
...  

Abstract Background The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Results Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. Conclusion Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.


2021 ◽  
Author(s):  
Joan E.M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.


2021 ◽  
Author(s):  
Mathias Martins ◽  
Maureen H.V. Fernandes ◽  
Lok R Joshi ◽  
Diego Diel

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 expressions levels of two key viral entry factors - ACE2 and TMPRSS2 - in the upper respiratory tract of aged ferrets.


2021 ◽  
Author(s):  
Bradley Fevrier

The current SARS-CoV-2 (coronavirus) outbreak has reached pandemic proportions with a large global imprint. In December 2019, COVID-19 was first reported in Wuhan, Hubei Province, China and has continued largely unabated. The SARS-CoV-2 (coronavirus) is much talked about currently; however, it is worth noting that there are several different coronaviruses known to man, with most of them being responsible for causing illness in animals. Seven (7) types of coronaviruses are identified as causing illnesses in humans. Of the seven human coronavirus infections, four involve mild upper respiratory tract complaints that produce slight symptoms of the common cold. Conversely, the other three human coronavirus infections present more severe consequences as recently demonstrated by the SARS-CoV-2. These deadly outbreaks of pneumonia can have consequences that are far-reaching and are global in nature. SARS-CoV was the first new viral pandemic of the 21st century. It had its beginnings in southern China during November 2002 having started mysteriously; It was contained in 2004 after having spread to five continents and thirty-three countries, infecting approximately 8000 people. MERS-CoV the virus that the causes Middle East respiratory syndrome (MERS) was first identified in 2012 in Saudi Arabia and Jordan and has since registered roughly 2,220 confirmed cases and 790 deaths.


2021 ◽  
pp. eabh0755
Author(s):  
Neeltje van Doremalen ◽  
Jyothi N. Purushotham ◽  
Jonathan E. Schulz ◽  
Myndi G. Holbrook ◽  
Trenton Bushmaker ◽  
...  

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.


Author(s):  
Muge Cevik ◽  
Matthew Tate ◽  
Oliver Lloyd ◽  
Alberto Enrico Maraolo ◽  
Jenna Schafers ◽  
...  

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.


2021 ◽  
pp. 25-29
Author(s):  
Patorn Piromchai ◽  
Chayakorn Phannikul ◽  
Sanguansak Thanaviratananich

<b><i>Background/Aims:</i></b> Nasal saline irrigation is a common procedure to relieve nasal symptoms in upper respiratory tract diseases. There is no consensus on the recommended nasal saline delivery devices. The objectives of this study were to evaluate efficacy, satisfaction, adherence, and adverse effects in patients with acute upper respiratory tract diseases using a syringe with a nasal applicator for nasal irrigation. <b><i>Methods:</i></b> Patients with acute nasopharyngitis, acute rhinitis, or acute rhinosinusitis were randomly allocated to use either (1) a syringe with a nasal applicator or (2) a syringe alone to irrigate one nostril. After the patients had completed irrigation with the allocated device in one nostril, they were instructed to perform nasal irrigation using the other device in the other nostril. All patients were instructed to use a syringe with a nasal applicator at home. The efficacy, satisfaction scores, adherence, and adverse effects were recorded. <b><i>Results:</i></b> Sixty-four patients were enrolled. The mean age of the patients was 33.95 years (18–59 years). The mean duration of symptoms was 4.80 days. None of the enrolled patients regularly performed nasal irrigation. Forty-two had acute nasopharyngitis, 10 had acute rhinitis, and 12 had acute rhinosinusitis. At baseline, the mean overall efficacy score for the syringe with a nasal applicator was 8.17 ± 1.43, and that for the syringe alone was 5.95 ± 2.02 (MD 2.23, <i>p</i> &#x3c; 0.001, 95% CI 1.75–2.70). At 1 week, the syringe with the nasal applicator had significantly higher scores in 3 of 4 domains, including symptom relief, ease of use, and patients’ willingness to recommend the device to others, compared to baseline (<i>p</i> &#x3c; 0.05). None of the enrolled patients had epistaxis, retained/dislodged the applicator during irrigation, or experienced an allergic reaction to the applicator after 1 week of nasal irrigation. <b><i>Conclusion:</i></b> Use of a syringe with an applicator for nasal irrigation yielded high scores in overall efficacy.


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