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Journal ArticleDOI

Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development.

TL;DR: It is found that SARS-CoV-2 isolates replicate efficiently in the lungs of Syrian hamsters and cause severe pathological lesions in the lung of these animals similar to commonly reported imaging features of COVID-19 patients with pneumonia.
Abstract: At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2-infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation SARS-CoV-2-infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2 Moreover, passive transfer of convalescent serum to naive hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs
Citations
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Journal ArticleDOI
23 Sep 2020-Nature
TL;DR: The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years. The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.

1,515 citations

Journal ArticleDOI
04 Dec 2020-Science
TL;DR: The vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein, and titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

974 citations

Journal ArticleDOI
18 Dec 2020-Science
TL;DR: The current dominant structural variant of SARS-CoV-2 appears to have evolved from the ancestral form and enhances transmissibility, and the mutation renders the new virus variant more susceptible to neutralizing antisera without altering the efficacy of vaccine candidates currently under development.
Abstract: The spike aspartic acid–614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.

742 citations

Journal ArticleDOI
23 Sep 2020-Nature
TL;DR: The findings of a World Health Organization expert working group that is developing animal models to test vaccines and therapeutic agents for the treatment of COVID-19, and their relevance for preclinical testing, are reviewed.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.

630 citations

Journal ArticleDOI
TL;DR: The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus.

619 citations

References
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Journal ArticleDOI
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.

36,578 citations


"Syrian hamsters as a small animal m..." refers background in this paper

  • ...C. Huang et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China....

    [...]

  • ...L. Mao et al., Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China....

    [...]

  • ...Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development Masaki Imaia,1, Kiyoko Iwatsuki-Horimotoa,1, Masato Hattab,1, Samantha Loeberc,1, Peter J. Halfmannb,1, Noriko Nakajimad,1, Tokiko Watanabea, Michiko Ujiea, Kenta Takahashid, Mutsumi Itoa, Shinya Yamadaa, Shufang Fanb, Shiho Chibab, Makoto Kurodab, Lizheng Guanb, Kosuke Takadaa, Tammy Armbrustb, Aaron Baloghb, Yuri Furusawaa, Moe Okudaa, Hiroshi Uekia, Atsuhiro Yasuharaa, Yuko Sakai-Tagawaa, Tiago J. S. Lopesa,b, Maki Kisoa, Seiya Yamayoshia, Noriko Kinoshitae, Norio Ohmagarie, Shin-ichiro Hattorie, Makoto Takedaf, Hiroaki Mitsuyae, Florian Krammerg, Tadaki Suzukid, and Yoshihiro Kawaokaa,b,h,2 aDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan; bInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711; cDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706; dDepartment of Pathology, National Institute of Infectious Diseases, 162-8640 Tokyo, Japan; eDisease Control and Prevention Center, National Center for Global Health and Medicine, 162-8655 Tokyo, Japan; fDepartment of Virology 3, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan; gDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and hDepartment of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan Edited by Robert L. Coffman, University of California, Santa Cruz, CA, and approved June 12, 2020 (received for review May 15, 2020) At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy....

    [...]

  • ...At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) that causes respiratory disease in and transmits among humans was detected in Wuhan, China (1, 2)....

    [...]

Journal ArticleDOI
TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

21,455 citations


"Syrian hamsters as a small animal m..." refers background in this paper

  • ...Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development Masaki Imaia,1, Kiyoko Iwatsuki-Horimotoa,1, Masato Hattab,1, Samantha Loeberc,1, Peter J. Halfmannb,1, Noriko Nakajimad,1, Tokiko Watanabea, Michiko Ujiea, Kenta Takahashid, Mutsumi Itoa, Shinya Yamadaa, Shufang Fanb, Shiho Chibab, Makoto Kurodab, Lizheng Guanb, Kosuke Takadaa, Tammy Armbrustb, Aaron Baloghb, Yuri Furusawaa, Moe Okudaa, Hiroshi Uekia, Atsuhiro Yasuharaa, Yuko Sakai-Tagawaa, Tiago J. S. Lopesa,b, Maki Kisoa, Seiya Yamayoshia, Noriko Kinoshitae, Norio Ohmagarie, Shin-ichiro Hattorie, Makoto Takedaf, Hiroaki Mitsuyae, Florian Krammerg, Tadaki Suzukid, and Yoshihiro Kawaokaa,b,h,2 aDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan; bInfluenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711; cDepartment of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706; dDepartment of Pathology, National Institute of Infectious Diseases, 162-8640 Tokyo, Japan; eDisease Control and Prevention Center, National Center for Global Health and Medicine, 162-8655 Tokyo, Japan; fDepartment of Virology 3, National Institute of Infectious Diseases, 208-0011 Tokyo, Japan; gDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; and hDepartment of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, 108-8639 Tokyo, Japan Edited by Robert L. Coffman, University of California, Santa Cruz, CA, and approved June 12, 2020 (received for review May 15, 2020) At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy....

    [...]

  • ...C. Huang et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China....

    [...]

  • ...L. Mao et al., Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China....

    [...]

  • ...At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) that causes respiratory disease in and transmits among humans was detected in Wuhan, China (1, 2)....

    [...]

Journal ArticleDOI
03 Feb 2020-Nature
TL;DR: Identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China, and it is shown that this virus belongs to the species of SARSr-CoV, indicates that the virus is related to a bat coronav virus.
Abstract: Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1–4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5–7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV. Characterization of full-length genome sequences from patients infected with a new coronavirus (2019-nCoV) shows that the sequences are nearly identical and indicates that the virus is related to a bat coronavirus.

16,857 citations

Journal ArticleDOI
16 Apr 2020-Cell
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.

15,362 citations


"Syrian hamsters as a small animal m..." refers background in this paper

  • ...M. Hoffmann et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor....

    [...]

  • ...The entry of SARS-CoV-2 to target cells is initiated by the binding of its spike (S) glycoprotein to a receptor, human angiotensinconverting enzyme 2 (ACE2) (6, 7)....

    [...]

  • ...Computational modeling suggests that ACE2 from Chinese hamster could interact with the S glycoprotein of SARS-CoV-2 (22)....

    [...]

  • ...Although ACE2 expression in NCI-H322 and NCI-H358 cells has not been examined, these cells may also express ACE2 at low levels....

    [...]

  • ...The entry of SARS-CoV-2 to target cells is initiated by the binding of its spike (S) glycoprotein to a receptor, human angiotensinconverting enzyme 2 (ACE2) (6, 7)....

    [...]

Journal ArticleDOI
26 May 2020-JAMA
TL;DR: This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area and assesses outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death.
Abstract: Importance There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19). Objective To describe the clinical characteristics and outcomes of patients with COVID-19 hospitalized in a US health care system. Design, Setting, and Participants Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates. Exposures Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample among patients requiring admission. Main Outcomes and Measures Clinical outcomes during hospitalization, such as invasive mechanical ventilation, kidney replacement therapy, and death. Demographics, baseline comorbidities, presenting vital signs, and test results were also collected. Results A total of 5700 patients were included (median age, 63 years [interquartile range {IQR}, 52-75; range, 0-107 years]; 39.7% female). The most common comorbidities were hypertension (3026; 56.6%), obesity (1737; 41.7%), and diabetes (1808; 33.8%). At triage, 30.7% of patients were febrile, 17.3% had a respiratory rate greater than 24 breaths/min, and 27.8% received supplemental oxygen. The rate of respiratory virus co-infection was 2.1%. Outcomes were assessed for 2634 patients who were discharged or had died at the study end point. During hospitalization, 373 patients (14.2%) (median age, 68 years [IQR, 56-78]; 33.5% female) were treated in the intensive care unit care, 320 (12.2%) received invasive mechanical ventilation, 81 (3.2%) were treated with kidney replacement therapy, and 553 (21%) died. As of April 4, 2020, for patients requiring mechanical ventilation (n = 1151, 20.2%), 38 (3.3%) were discharged alive, 282 (24.5%) died, and 831 (72.2%) remained in hospital. The median postdischarge follow-up time was 4.4 days (IQR, 2.2-9.3). A total of 45 patients (2.2%) were readmitted during the study period. The median time to readmission was 3 days (IQR, 1.0-4.5) for readmitted patients. Among the 3066 patients who remained hospitalized at the final study follow-up date (median age, 65 years [IQR, 54-75]), the median follow-up at time of censoring was 4.5 days (IQR, 2.4-8.1). Conclusions and Relevance This case series provides characteristics and early outcomes of sequentially hospitalized patients with confirmed COVID-19 in the New York City area.

7,282 citations

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