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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329545

ABSTRACT

Wildlife animals may be susceptible for multiple infectious agents of public health or veterinary relevance, thereby potentially forming a reservoir that bears the constant risk of re-introduction into the human or livestock population. Here, we serologically investigated 493 wild ruminant samples collected in the 2021/22 hunting season in Germany for the presence of antibodies against the severe acute respiratory coronavirus 2 (SARS-CoV-2) and four viruses pathogenic for domestic ruminants, namely the orthobunyavirus Schmallenberg virus (SBV), the reovirus bluetongue virus (BTV) and ruminant pestiviruses like bovine viral diarrhoea virus or border disease virus. The animal species comprised fallow deer, red deer, roe deer, mouflon and wisent. For coronavirus serology, additional 307 fallow, roe and red deer samples collected between 2017 and 2020 at three military training areas were included. While antibodies against SBV could be detected in about 13.6% of the samples collected in 2021/22, only one fallow deer of unknown age tested positive for anti-BTV antibodies and all samples reacted negative for antibodies against ruminant pestiviruses. In an ELISA based on the receptor-binding domain (RBD) of SARS-CoV-2, 25 out of 493 (5.1%) samples collected in autumn and winter 2021/22 scored positive. This sero-reactivity could not be confirmed by the highly specific virus neutralization test, occurred also in 2017, 2018 and 2019, i.e. prior to the human SARS-CoV-2 pandemic, and was likewise observed against the RBD of the related SARS-CoV-1. Therefore, the SARS-CoV-2-seroreactivity was most likely induced by another, hitherto unknown deer virus belonging to the subgenus Sarbecovirus of betacoronaviruses.

2.
Nature ; 602(7896): 307-313, 2022 02.
Article in English | MEDLINE | ID: covidwho-1585832

ABSTRACT

Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.


Subject(s)
COVID-19/transmission , COVID-19/virology , Mutation , SARS-CoV-2/classification , SARS-CoV-2/physiology , Virus Replication , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Animals, Laboratory/virology , COVID-19/veterinary , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Humans , Male , Mesocricetus/virology , Mice , Mice, Transgenic , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virulence/genetics
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-293969

ABSTRACT

Background: A novel zoonotic SARS-related coronavirus emerged in China at the end of 2019. The novel SARS-CoV-2 became pandemic within weeks and the number of human infections and severe cases is increasing. The role of potential animal hosts is still understudied.Methods: We intranasally inoculated fruit bats (Rousettus aegyptiacus;n=9), ferrets (n=9), pigs (n=9) and chickens (n=17) with 105 TCID50 of a SARS-CoV-2 isolate per animal. Animals were monitored clinically and for virus shedding. Direct contact animals (n=3) were included. Animals were humanely sacrificed for virological and immune-pathohistological analysis at different time points.Findings: Under these settings, pigs and chickens were not susceptible to SARS-CoV-2. All swabs as well as organ samples and contact animals remained negative for viral RNA, and none of the animals seroconverted. Rousettus aegyptiacus fruit bats experienced a transient infection, with virus detectable by RT-qPCR, immunohistochemistry (IHC) and in situ hybridization (ISH) in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung and lung associated lymphatic tissue. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets with transmission to all direct contact animals. Prominent viral RNA loads of up to 104 viral genome copies/ml were detected in the upper respiratory tract. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Both fruit bats and ferrets developed SARS-CoV-2 reactive antibodies reaching neutralizing titers of up to 1:1024.Interpretation: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. These animals might serve as a useful model for further studies e.g. testing vaccines or antivirals.Funding Statement: Intramural funding of the German Federal Ministry of Food and Agriculture provided to the Friedrich-Loeffler-Institut.Declaration of Interests: All authors declare no competing interest.Ethics Approval Statement: The animal experiments were evaluated and approved by the ethics committee of the State Office of Agriculture, Food safety, and Fishery in Mecklenburg – Western Pomerania (LALLF M-V: LVL MV/TSD/7221.3-2-010/18-12). All procedures were carried out in approved biosafety level 3 (BSL3) facilities.

4.
Viruses ; 13(8)2021 08 19.
Article in English | MEDLINE | ID: covidwho-1367921

ABSTRACT

The recent emergence of SARS-CoV-2 in humans from a yet unidentified animal reservoir and the capacity of the virus to naturally infect pets, farmed animals and potentially wild animals has highlighted the need for serological surveillance tools. In this study, the luciferase immunoprecipitation systems (LIPS), employing the spike (S) and nucleocapsid proteins (N) of SARS-CoV-2, was used to examine the suitability of the assay for antibody detection in different animal species. Sera from SARS-CoV-2 naturally-infected mink (n = 77), SARS-CoV-2 experimentally-infected ferrets, fruit bats and hamsters and a rabbit vaccinated with a purified spike protein were examined for antibodies using the SARS-CoV-2 N and/or S proteins. From comparison with the known neutralization status of the serum samples, statistical analyses including calculation of the Spearman rank-order-correlation coefficient and Cohen's kappa agreement were used to interpret the antibody results and diagnostic performance. The LIPS immunoassay robustly detected the presence of viral antibodies in naturally infected SARS-CoV-2 mink, experimentally infected ferrets, fruit bats and hamsters as well as in an immunized rabbit. For the SARS-CoV-2-LIPS-S assay, there was a good level of discrimination between the positive and negative samples for each of the five species tested with 100% agreement with the virus neutralization results. In contrast, the SARS-CoV-2-LIPS-N assay did not consistently differentiate between SARS-CoV-2 positive and negative sera. This study demonstrates the suitability of the SARS-CoV-2-LIPS-S assay for the sero-surveillance of SARS-CoV-2 infection in a range of animal species.


Subject(s)
Antibodies, Viral/blood , COVID-19/veterinary , Mink/immunology , SARS-CoV-2/immunology , Animals , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing , Chiroptera/immunology , Coronavirus Nucleocapsid Proteins/immunology , Epidemiological Monitoring , Ferrets/immunology , Immunoprecipitation , Mesocricetus/immunology , Phosphoproteins/immunology , Rabbits/immunology , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/immunology
5.
One Health ; 13: 100313, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1364384

ABSTRACT

Assays to measure SARS-CoV-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts. A recently developed assay, the surrogate virus-neutralization test (sVNT) is a quick and commercially available alternative to the "gold standard" virus neutralization assay using authentic virus, and does not require processing at BSL-3 level. The assay relies on the inhibition of binding of the receptor binding domain (RBD) on the spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) by antibodies present in sera. As the sVNT does not require species- or isotype-specific conjugates, it can be similarly used for antibody detection in human and animal sera. In this study, we used 298 sera from PCR-confirmed COVID-19 patients and 151 sera from patients confirmed with other coronavirus or other (respiratory) infections, to evaluate the performance of the sVNT. To analyze the use of the assay in a One Health setting, we studied the presence of RBD-binding antibodies in 154 sera from nine animal species (cynomolgus and rhesus macaques, ferrets, rabbits, hamsters, cats, cattle, mink and dromedary camels). The sVNT showed a moderate to high sensitivity and a high specificity using sera from confirmed COVID-19 patients (91.3% and 100%, respectively) and animal sera (93.9% and 100%), however it lacked sensitivity to detect low titers. Significant correlations were found between the sVNT outcomes and PRNT50 and the Wantai total Ig and IgM ELISAs. While species-specific validation will be essential, our results show that the sVNT holds promise in detecting RBD-binding antibodies in multiple species.

6.
Nat Commun ; 12(1): 4048, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1290662

ABSTRACT

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Cell Line , Chlorocebus aethiops , Genome, Viral/genetics , Humans , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells
7.
Emerg Infect Dis ; 27(7): 1974-1976, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278359

ABSTRACT

We report a therapy cat in a nursing home in Germany infected with severe acute respiratory syndrome coronavirus 2 during a cluster outbreak in the home residents. Although we confirmed prolonged presence of virus RNA in the asymptomatic cat, genome sequencing showed no further role of the cat in human infections on site.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Cats , Disease Outbreaks , Germany , Humans , RNA, Viral/genetics , Retirement
8.
Viruses ; 13(6)2021 05 27.
Article in English | MEDLINE | ID: covidwho-1256663

ABSTRACT

Registered cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the German human population increased rapidly during the second wave of the SARS-CoV-2 pandemic in winter 2020/21. Since domestic cats are susceptible to SARS-CoV-2, the occurrence of trans-species transmission needs to be monitored. A previous serosurvey during the first wave of the pandemic detected antibodies against SARS-CoV-2 in 0.65% of feline serum samples that were randomly sampled across Germany. In the here-presented follow-up study that was conducted from September 2020 to February 2021, the seroprevalence rose to 1.36% (16/1173). This doubling of the seroprevalence in cats is in line with the rise of reported cases in the human population and indicates a continuous occurrence of trans-species transmission from infected owners to their cats.


Subject(s)
Antibodies, Viral/blood , COVID-19/veterinary , Cat Diseases/epidemiology , SARS-CoV-2/immunology , Animals , Animals, Domestic , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/transmission , Cat Diseases/diagnosis , Cat Diseases/transmission , Cats , Germany/epidemiology , Humans , Prevalence , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Zoonoses/diagnosis , Zoonoses/epidemiology , Zoonoses/transmission
9.
Viruses ; 13(3)2021 03 23.
Article in English | MEDLINE | ID: covidwho-1154524

ABSTRACT

The visualization of viral pathogens in infected tissues is an invaluable tool to understand spatial virus distribution, localization, and cell tropism in vivo. Commonly, virus-infected tissues are analyzed using conventional immunohistochemistry in paraffin-embedded thin sections. Here, we demonstrate the utility of volumetric three-dimensional (3D) immunofluorescence imaging using tissue optical clearing and light sheet microscopy to investigate host-pathogen interactions of pandemic SARS-CoV-2 in ferrets at a mesoscopic scale. The superior spatial context of large, intact samples (>150 mm3) allowed detailed quantification of interrelated parameters like focus-to-focus distance or SARS-CoV-2-infected area, facilitating an in-depth description of SARS-CoV-2 infection foci. Accordingly, we could confirm a preferential infection of the ferret upper respiratory tract by SARS-CoV-2 and suggest clustering of infection foci in close proximity. Conclusively, we present a proof-of-concept study for investigating critically important respiratory pathogens in their spatial tissue morphology and demonstrate the first specific 3D visualization of SARS-CoV-2 infection.


Subject(s)
COVID-19/virology , Ferrets , Microscopy/methods , Respiratory System/virology , SARS-CoV-2/physiology , Animals , Disease Models, Animal , Ferrets/virology , Humans , Respiratory System/anatomy & histology , SARS-CoV-2/genetics
10.
Emerg Infect Dis ; 27(4): 1193-1195, 2021 04.
Article in English | MEDLINE | ID: covidwho-1146550

ABSTRACT

After experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Thus, bank voles are unlikely to establish effective transmission cycles in nature.


Subject(s)
Arvicolinae , COVID-19 , Disease Transmission, Infectious , Rodent Diseases , Seroconversion , Virus Shedding , Animals , Antibodies, Viral , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , COVID-19 Serological Testing , Disease Models, Animal , Disease Susceptibility , Nasal Mucosa/virology , Rodent Diseases/immunology , Rodent Diseases/transmission , Rodent Diseases/virology
11.
Nature ; 592(7852): 122-127, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104508

ABSTRACT

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.


Subject(s)
COVID-19/transmission , COVID-19/virology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Bronchi/cytology , Bronchi/virology , COVID-19/epidemiology , Cell Line , Cells, Cultured , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Founder Effect , Gene Knock-In Techniques , Genetic Fitness , Humans , Male , Mesocricetus , Mice , Nasal Mucosa/cytology , Nasal Mucosa/virology , Protein Binding , RNA, Viral/analysis , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
12.
Lancet Microbe ; 1(5): e218-e225, 2020 09.
Article in English | MEDLINE | ID: covidwho-1087372

ABSTRACT

BACKGROUND: In December, 2019, a novel zoonotic severe acute respiratory syndrome-related coronavirus emerged in China. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became pandemic within weeks and the number of human infections and severe cases is increasing. We aimed to investigate the susceptibilty of potential animal hosts and the risk of anthropozoonotic spill-over infections. METHODS: We intranasally inoculated nine fruit bats (Rousettus aegyptiacus), ferrets (Mustela putorius), pigs (Sus scrofa domesticus), and 17 chickens (Gallus gallus domesticus) with 105 TCID50 of a SARS-CoV-2 isolate per animal. Direct contact animals (n=3) were included 24 h after inoculation to test viral transmission. Animals were monitored for clinical signs and for virus shedding by nucleic acid extraction from nasal washes and rectal swabs (ferrets), oral swabs and pooled faeces samples (fruit bats), nasal and rectal swabs (pigs), or oropharyngeal and cloacal swabs (chickens) on days 2, 4, 8, 12, 16, and 21 after infection by quantitative RT-PCR (RT-qPCR). On days 4, 8, and 12, two inoculated animals (or three in the case of chickens) of each species were euthanised, and all remaining animals, including the contacts, were euthanised at day 21. All animals were subjected to autopsy and various tissues were collected for virus detection by RT-qPCR, histopathology immunohistochemistry, and in situ hybridisation. Presence of SARS-CoV-2 reactive antibodies was tested by indirect immunofluorescence assay and virus neutralisation test in samples collected before inoculation and at autopsy. FINDINGS: Pigs and chickens were not susceptible to SARS-CoV-2. All swabs, organ samples, and contact animals were negative for viral RNA, and none of the pigs or chickens seroconverted. Seven (78%) of nine fruit bats had a transient infection, with virus detectable by RT-qPCR, immunohistochemistry, and in situ hybridisation in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung, and lung-associated lymphatic tissue in two animals euthanised at day 4. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets, with transmission to all three direct contact animals. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Prominent viral RNA loads of 0-104 viral genome copies per mL were detected in the upper respiratory tract of fruit bats and ferrets, and both species developed SARS-CoV-2-reactive antibodies reaching neutralising titres of up to 1/1024 after 21 days. INTERPRETATION: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. Ferrets might serve as a useful model for further studies-eg, testing vaccines or antivirals. FUNDING: German Federal Ministry of Food and Agriculture.


Subject(s)
COVID-19 , Chiroptera , Rhinitis , Animals , Antibodies, Viral , COVID-19/veterinary , Chickens/genetics , Chiroptera/genetics , Ferrets/genetics , RNA, Viral/genetics , SARS-CoV-2
13.
Vaccines (Basel) ; 8(4)2020 Dec 17.
Article in English | MEDLINE | ID: covidwho-979710

ABSTRACT

Domestic cats (Felis catus) are popular companion animals that live in close contact with their human owners. Therefore, the risk of a trans-species spreading event between domestic cats and humans is ever-present. Shortly after the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread around the world, the role of domestic cats in the transmission cycle was questioned. In the present study, the first large-scale survey of antibody occurrence in the domestic cat population in Germany was conducted, in order to assess the incidence of naturally occurring human to cat transmission of SARS-CoV-2. A total of 920 serum samples, which were collected from April to September of 2020, were screened by an indirect multispecies ELISA. Positive samples were verified using an indirect immunofluorescence test (iIFT) and additionally tested for neutralizing antibodies. Furthermore, serum samples were screened for antibodies against feline coronavirus (FCoV), in order to rule out cross-reactivity in the described test systems. Overall, 0.69% (6/920) of serum samples were found to be positive for antibodies against SARS-CoV-2 by ELISA and iIFT. Two of these reactive sera also displayed neutralizing antibodies. No cross-reactivity with FCoV-specific antibodies was observed. The finding of SARS-CoV-2 antibody-positive serum samples in the domestic cat population of Germany, during a period when the incidence of human infection in the country was still rather low, indicates that human-to-cat transmission of SARS-CoV-2 happens, but there is no indication of SARS-CoV-2 circulation in cats.

14.
Transbound Emerg Dis ; 68(4): 1779-1785, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-944802

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of infected humans and hundreds of thousands of fatalities. As the novel disease - referred to as COVID-19 - unfolded, occasional anthropozoonotic infections of animals by owners or caretakers were reported in dogs, felid species and farmed mink. Further species were shown to be susceptible under experimental conditions. The extent of natural infections of animals, however, is still largely unknown. Serological methods will be useful tools for tracing SARS-CoV-2 infections in animals once test systems are evaluated for use in different species. Here, we developed an indirect multi-species ELISA based on the receptor-binding domain (RBD) of SARS-CoV-2. The newly established ELISA was evaluated using 59 sera of infected or vaccinated animals, including ferrets, raccoon dogs, hamsters, rabbits, chickens, cattle and a cat, and a total of 220 antibody-negative sera of the same animal species. Overall, a diagnostic specificity of 100.0% and sensitivity of 98.31% were achieved, and the functionality with every species included in this study could be demonstrated. Hence, a versatile and reliable ELISA protocol was established that enables high-throughput antibody detection in a broad range of animal species, which may be used for outbreak investigations, to assess the seroprevalence in susceptible species or to screen for reservoir or intermediate hosts.


Subject(s)
COVID-19 , Cat Diseases , Cattle Diseases , Rodent Diseases , Animals , Antibodies, Viral , COVID-19/veterinary , Cat Diseases/virology , Cats , Cattle , Cattle Diseases/virology , Chickens , Enzyme-Linked Immunosorbent Assay/veterinary , Ferrets , Humans , Mice , Rabbits , Rodent Diseases/virology , SARS-CoV-2 , Seroepidemiologic Studies
15.
bioRxiv ; 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-915978

ABSTRACT

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic 1 . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

16.
Emerg Infect Dis ; 26(12): 2982-2985, 2020 12.
Article in English | MEDLINE | ID: covidwho-890311

ABSTRACT

Raccoon dogs might have been intermediate hosts for severe acute respiratory syndrome-associated coronavirus in 2002-2004. We demonstrated susceptibility of raccoon dogs to severe acute respiratory syndrome coronavirus 2 infection and transmission to in-contact animals. Infected animals had no signs of illness. Virus replication and tissue lesions occurred in the nasal conchae.


Subject(s)
COVID-19/transmission , SARS-CoV-2/genetics , Animals , COVID-19/virology , Disease Models, Animal , Disease Susceptibility/virology , Pandemics , Raccoon Dogs/virology , Reverse Transcriptase Polymerase Chain Reaction , Viral Zoonoses , Virus Shedding
17.
Emerg Infect Dis ; 26(12): 2979-2981, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-842514

ABSTRACT

We inoculated 6 cattle with severe acute respiratory syndrome coronavirus 2 and kept them together with 3 uninoculated cattle. We observed viral replication and specific seroreactivity in 2 inoculated animals, despite high levels of preexisting antibody titers against a bovine betacoronavirus. The in-contact animals did not become infected.


Subject(s)
COVID-19/transmission , SARS-CoV-2/genetics , Animals , Cattle/virology , Pandemics , Reverse Transcriptase Polymerase Chain Reaction , Viral Zoonoses/transmission , Virus Replication
18.
Viruses ; 12(7):779, 2020.
Article | WHO COVID | ID: covidwho-650369

ABSTRACT

In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients.

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