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1.
mBio ; 11(3)2020 05 22.
Article in English | MEDLINE | ID: covidwho-1723548

ABSTRACT

Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antiviral Agents/pharmacology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/virology , Disease Models, Animal , Female , Ferrets , Humans , Hydroxychloroquine/therapeutic use , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , United States , United States Food and Drug Administration , Viral Load
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-320007

ABSTRACT

Memory T-cell responses have been demonstrated after recovery from SARS-CoV-2 infection, but the phenotypes of SARS-CoV-2-specific T cells have not been comprehensively investigated ex vivo. We detected SARS-CoV-2-specific CD8+ T cells by MHC-I multimer staining and examined their phenotypes in relation to their functional capacity in acute and convalescent COVID-19. In the convalescent phase, multimer+ cells exhibited early differentiated effector-memory phenotypes. The frequency of CD127+KLRG1- memory precursor effector cells among multimer+ cells was significantly lower in convalescent individuals with severe disease than those with mild disease. Cytokine-secretion assays combined with MHC-I multimer staining revealed that the proportion of IFN-γ-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to other viruses. Importantly, the proportion of IFN-γ-producing cells was significantly higher in PD-1+ cells than PD-1- cells among multimer+ cells in both the acute and convalescence phases, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our findings provide insights for effective vaccine development.

4.
Nat Commun ; 13(1): 21, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616983

ABSTRACT

While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Disease Models, Animal , SARS-CoV-2/immunology , Virus Shedding/immunology , Age Factors , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/genetics , COVID-19/transmission , Chlorocebus aethiops , Female , Ferrets , Gene Expression Profiling/methods , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Vero Cells , Virulence
5.
Int J Environ Res Public Health ; 18(21)2021 10 29.
Article in English | MEDLINE | ID: covidwho-1512290

ABSTRACT

This participatory action research study was conducted to confirm the implementation process and effect of developing and applying a preceptor education program based on the One-Minute Preceptor Model to foster the competence of preceptor clinical nurses. The study was conducted for eight weeks from March 2020 on 30 preceptor nurses in South Korea. Nursing standards were developed for two weeks and six cycles (comprising four stages) were performed. Data collection was integrated using both quantitative and qualitative approaches. For quantitative data, the Clinical Core Competency of Preceptor (CCCP) and General Communication Competence Scale (GICC-15) results were collected from preceptor nurses through questionnaires. Reflection journals of nurses' experiences were also analyzed through content analysis and frequency of keywords using WordClouds. There was no significant change in CCCP or GICC-15 results among preceptor nurses. However, nurses' experiences were associated with the growth and development of competencies such as evidence-based practice, quality feedback, and self-reflection. The program was effective in developing nurse competencies. Therefore, it is necessary to encourage One-Minute Preceptor Model activities among preceptors through an action research approach and to actively support research and practice in clinical settings, as well as to provide organizational and systematic support.


Subject(s)
Clinical Competence , Preceptorship , Evidence-Based Practice , Health Services Research , Humans , Program Evaluation , Surveys and Questionnaires
8.
Signal Transduct Target Ther ; 6(1): 203, 2021 05 22.
Article in English | MEDLINE | ID: covidwho-1387226
9.
J Allergy Clin Immunol ; 148(4): 996-1006.e18, 2021 10.
Article in English | MEDLINE | ID: covidwho-1330917

ABSTRACT

BACKGROUND: Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. OBJECTIVE: We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. METHODS: We performed RNA sequencing and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved PBMCs. RESULTS: In RNA-sequencing analysis, the NK cells exhibited distinctive features compared with healthy donors, with significant enrichment of proinflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg NK-cell population expanded in cryopreserved PBMCs from patients with COVID-19 regardless of disease severity, accompanied by decreased NK-cell cytotoxicity. The NK-cell population was rapidly normalized alongside the disappearance of unconventional CD56dimCD16neg NK cells and the recovery of NK-cell cytotoxicity in patients with mild COVID-19, but this occurred slowly in patients with severe COVID-19. CONCLUSIONS: The current longitudinal study provides a deep understanding of the NK-cell biology in COVID-19.


Subject(s)
COVID-19/immunology , Killer Cells, Natural/immunology , Lymphocyte Activation , SARS-CoV-2/immunology , Adult , COVID-19/pathology , Humans , Killer Cells, Natural/pathology , Longitudinal Studies , Male , Middle Aged , Prospective Studies , RNA-Seq
10.
Nat Commun ; 12(1): 4043, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1290767

ABSTRACT

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma/blood , Vaccination
11.
J Microbiol ; 59(5): 530-533, 2021 May.
Article in English | MEDLINE | ID: covidwho-1204981

ABSTRACT

To compare the standardized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence of high epicenter region with non-epicenter region, serological studies were performed with a total of 3,268 sera from Daegu City and 3,981 sera from Chungbuk Province. Indirect immunofluorescence assay (IFA) for SARS-CoV-2 IgG results showed a high seroprevalence rate in the Daegu City (epicenter) compared with a non-epicenter area (Chungbuk Province) (1.27% vs. 0.91%, P = 0.0358). It is noteworthy that the highest seroprevalence in Daegu City was found in elderly patients (70's) whereas young adult patients (20's) in Chungbuk Province showed the highest seroprevalence. Neutralizing antibody (NAb) titers were found in three samples from Daegu City (3/3, 268, 0.09%) while none of the samples from Chungbuk Province were NAb positive. These results demonstrated that even following the large outbreak, the seropositive rate of SARS-CoV-2 in the general population remained low in South Korea.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Seroepidemiologic Studies , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Middle Aged , Republic of Korea , Young Adult
12.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1065202

ABSTRACT

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
13.
Emerg Microbes Infect ; 10(1): 152-160, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1012800

ABSTRACT

Cases of laboratory-confirmed SARS-CoV-2 reinfection have been reported in a number of countries. Further, the level of natural immunity induced by SARS-CoV-2 infection is not fully clear, nor is it clear if a primary infection is protective against reinfection. To investigate the potential association between serum antibody titres and reinfection of SARS-CoV-2, ferrets with different levels of NAb titres after primary SARS-CoV-2 infection were subjected to reinfection with a heterologous SARS-CoV-2 strain. All heterologous SARS-CoV-2 reinfected ferrets showed active virus replication in the upper respiratory and gastro-intestinal tracts. However, the high NAb titre group showed attenuated viral replication and rapid viral clearance. In addition, direct-contact transmission was observed only from reinfected ferrets with low NAb titres (<20), and not from other groups. Further, lung histopathology demonstrated the presence of limited inflammatory regions in the high NAb titre groups compared with control and low NAb groups. This study demonstrates a close correlation between a low NAb titre and SARS-CoV-2 reinfection in a recovered ferret reinfection model.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/transmission , Reinfection/immunology , SARS-CoV-2/immunology , Animals , COVID-19/virology , Chlorocebus aethiops , Ferrets , Vero Cells
15.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-988082

ABSTRACT

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
16.
J Microbiol ; 58(10): 886-891, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-807667

ABSTRACT

Various treatments and agents had been reported to inactivate RNA viruses. Of these, thermal inactivation is generally considered an effective and cheap method of sample preparation for downstream assays. The purpose of this study is to establish a safe inactivation method for SARS-CoV-2 without compromising the amount of amplifiable viral genome necessary for clinical diagnoses. In this study, we demonstrate the infectivity and genomic stability of SARSCoV- 2 by thermal inactivation at both 56°C and 65°C. The results substantiate that viable SARS-CoV-2 is readily inactivated when incubated at 56°C for 30 min or at 65°C for 10 min. qRT-PCR of specimens heat-inactivated at 56°C for 30 min or 65°C for 15 min revealed similar genomic RNA stability compared with non-heat inactivated specimens. Further, we demonstrate that 30 min of thermal inactivation at 56°C could inactivate viable viruses from clinical COVID-19 specimens without attenuating the qRT-PCR diagnostic sensitivity. Heat treatment of clinical specimens from COVID-19 patients at 56°C for 30 min or 65°C for 15 min could be a useful method for the inactivation of a highly contagious agent, SARS-CoV-2. Use of this method would reduce the potential for secondary infections in BSL2 conditions during diagnostic procedures. Importantly, infectious virus can be inactivated in clinical specimens without compromising the sensitivity of the diagnostic RT-PCR assay.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/diagnosis , Pneumonia, Viral/virology , Specimen Handling/methods , Virus Inactivation , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/virology , Genome, Viral , Genomic Instability , Hot Temperature , Humans , Pandemics , Pneumonia, Viral/diagnosis , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
17.
Clin Microbiol Infect ; 26(11): 1520-1524, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-664085

ABSTRACT

OBJECTIVES: The aim was to determine whether various clinical specimens obtained from COVID-19 patients contain the infectious virus. METHODS: To demonstrate whether various clinical specimens contain the viable virus, we collected naso/oropharyngeal swabs and saliva, urine and stool samples from five COVID-19 patients and performed a quantitative polymerase chain reaction (qPCR) to assess viral load. Specimens positive with qPCR were subjected to virus isolation in Vero cells. We also used urine and stool samples to intranasally inoculate ferrets and evaluated the virus titres in nasal washes on 2, 4, 6 and 8 days post infection. RESULTS: SARS-CoV-2 RNA was detected in all naso/oropharyngeal swabs and saliva, urine and stool samples collected between days 8 and 30 of the clinical course. Notably, viral loads in urine, saliva and stool samples were almost equal to or higher than those in naso/oropharyngeal swabs (urine 1.08 ± 0.16-2.09 ± 0.85 log10 copies/mL, saliva 1.07 ± 0.34-1.65 ± 0.46 log10 copies/mL, stool 1.17 ± 0.32 log10 copies/mL, naso/oropharyngeal swabs 1.18 ± 0.12-1.34 ± 0.30 log10 copies/mL). Further, viable SARS-CoV-2 was isolated from naso/oropharyngeal swabs and saliva of COVID-19 patients, as well as nasal washes of ferrets inoculated with patient urine or stool. DISCUSSION: Viable SARS-CoV-2 was demonstrated in saliva, urine and stool samples from COVID-19 patients up to days 11-15 of the clinical course. This result suggests that viable SARS-CoV-2 can be secreted in various clinical samples and respiratory specimens.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Pneumonia, Viral/virology , Specimen Handling/methods , Animals , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Chlorocebus aethiops , Feces/virology , Female , Ferrets , Genome, Viral/genetics , Humans , Male , Microbial Viability , Middle Aged , Pandemics , Pharynx/virology , RNA, Viral/genetics , SARS-CoV-2 , Saliva/virology , Urine/virology , Vero Cells , Viral Load , Virus Shedding
18.
Sci Immunol ; 5(49)2020 07 10.
Article in English | MEDLINE | ID: covidwho-639363

ABSTRACT

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1ß-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1ß-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunophenotyping , Influenza A virus/immunology , Influenza, Human/immunology , Interferon Type I/metabolism , Pneumonia, Viral/immunology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/immunology , COVID-19 , Cells, Cultured , Coronavirus Infections/blood , Coronavirus Infections/virology , Female , Healthy Volunteers , Humans , Inflammation/immunology , Influenza, Human/blood , Influenza, Human/virology , Interleukin-1beta/metabolism , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , RNA-Seq , SARS-CoV-2 , Single-Cell Analysis , Transcriptome , Tumor Necrosis Factor-alpha/metabolism
19.
Am J Infect Control ; 48(7): 822-824, 2020 07.
Article in English | MEDLINE | ID: covidwho-155118
20.
Cell Host Microbe ; 27(5): 704-709.e2, 2020 05 13.
Article in English | MEDLINE | ID: covidwho-34929

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/transmission , Ferrets , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Animals , Antibodies, Viral/immunology , Betacoronavirus/immunology , COVID-19 , Disease Models, Animal , Pandemics , SARS-CoV-2 , Viral Vaccines/immunology , Virus Shedding
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