scholarly journals Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

2020 ◽  
Author(s):  
Allison Totura ◽  
Virginia Livingston ◽  
Ondraya Frick ◽  
David Dyer ◽  
Donald Nichols ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Small Particle ◽  
Severe Disease ◽  
Global Public Health ◽  
Highly Pathogenic ◽  
Initial Development ◽  
Aerosol Exposure ◽  
Coronavirus Infection ◽  
Dose Dependent ◽  
Green Monkeys

Abstract Emerging highly pathogenic coronaviruses (CoV) are a global public health threat due to the potential for person-to-person transmission and higher mortality rates than common seasonal respiratory pathogens. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in approximately 35% of human cases. Primate models of highly pathogenic coronavirus infection are needed to support development of therapeutics or vaccines, but few models exist that recapitulate severe disease signs. For initial development of a MERS-CoV primate model, twelve African green monkeys (AGMs) were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose-dependent increase of respiratory disease signs and viral titers in serum and throat swabs between the 103 PFU and the 105 PFU dose groups, although all AGMs survived for the 28 day duration of the study. This study is the first to describe dose-dependent effects of highly pathogenic coronavirus infection of primates and uses a route of infection (small particle aerosol) with potential relevance to MERS-CoV transmission in humans. Aerosol exposure of AGMs may provide a platform for the development of primate models of novel coronavirus disease, with potential utility in therapeutic development and viral pathogenesis studies.

scholarly journals Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

2020 ◽  
Author(s):  
Allison Totura ◽  
Virginia Livingston ◽  
Ondraya Frick ◽  
David Dyer ◽  
Donald Nichols ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Small Particle ◽  
Severe Disease ◽  
Global Public Health ◽  
Highly Pathogenic ◽  
Initial Development ◽  
Aerosol Exposure ◽  
Coronavirus Infection ◽  
Dose Dependent ◽  
Green Monkeys

Abstract Emerging highly pathogenic coronaviruses (CoV) are a global public health threat due to the potential for person-to-person transmission and higher mortality rates than common seasonal respiratory pathogens. Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012, causing lethal respiratory disease in approximately 35% of human cases.Primate models of highly pathogenic coronavirus infection are needed to support development of therapeutics or vaccines, but few models exist that recapitulate severe disease signs. For initial development of a MERS-CoV primate model, twelve African green monkeys (AGMs) were exposed to 103, 104, or 105 PFU target doses of aerosolized MERS-CoV. We observed a dose- dependent increase of respiratory disease signs and viral titers in serum and throat swabs between the 103 PFU and the 105 PFU dose groups, although all AGMs survived for the 28 day duration of the study. This study is the first to describe dose-dependent effects of highly pathogenic coronavirus infection of primates and uses a route of infection (small particle aerosol) with potential relevance to MERS-CoV transmission in humans. Aerosol exposure of AGMs may provide a platform for the development of primate models of novel coronavirus disease, with potential utility in therapeutic development and viral pathogenesis studies.

scholarly journals Small Particle Aerosol Exposure of African Green Monkeys to MERS-CoV as a Model for Highly Pathogenic Coronavirus Infection

2020 ◽  
Vol 26 (12) ◽  
pp. 2835-2843 ◽  
Author(s):  
Allison Totura ◽  
Virginia Livingston ◽  
Ondraya Frick ◽  
David Dyer ◽  
Donald Nichols ◽  
...  
Keyword(s):  
Small Particle ◽  
Highly Pathogenic ◽  
Aerosol Exposure ◽  
Coronavirus Infection ◽  
Green Monkeys

scholarly journals Aerosol Exposure of Cynomolgus Macaques to SARS-CoV-2 Results in More Severe Pathology than Existing Models

2021 ◽  
Author(s):  
Sandra L. Bixler ◽  
Christopher P. Stefan ◽  
Alexandra Jay ◽  
Franco Rossi ◽  
Keersten M. Ricks ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Severe Disease ◽  
Clinical Signs ◽  
Primate Species ◽  
Clinical Endpoints ◽  
Aerosol Exposure ◽  
Cynomolgus Macaques ◽  
Severe Pathology ◽  
Selection Testing ◽  
Medical Countermeasures

AbstractThe emergence of SARS-CoV-2 pandemic has highlighted the need for animal models that faithfully recapitulate the salient features of COVID-19 disease in humans; these models are necessary for the rapid down-selection, testing, and evaluation of medical countermeasures. Here we performed a direct comparison of two distinct routes of SARS-CoV-2 exposure, combined intratracheal/intranasal and small particle aerosol, in two nonhuman primate species: rhesus and cynomolgus macaques. While all four experimental groups displayed very few outward clinical signs, evidence of mild to moderate respiratory disease was present on radiographs and at the time of necropsy. Cynomolgus macaques exposed via the aerosol route also developed the most consistent fever responses and had the most severe respiratory disease and pathology. This study demonstrates that while all four models were suitable representations of mild COVID-like illness, aerosol exposure of cynomolgus macaques to SARS-CoV-2 produced the most severe disease, which may provide additional clinical endpoints for evaluating therapeutics and vaccines.

Impact of Novel Coronavirus (COVID-19) on Pregnant Women: A Review

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Saima Habeeb ◽  
Manju Chugani
Keyword(s):  
Pregnant Women ◽  
Vertical Transmission ◽  
Respiratory Infections ◽  
Age Groups ◽  
Well Being ◽  
Fetal Outcome ◽  
Global Public Health ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
The Impact

: The novel coronavirus infection (COVID‐19) is a global public health emergency.Since its outbreak in Wuhan, China in December 2019, the infection has spread at an alarming rate across the globe and humans have been locked down to their countries, cities and homes. As of now, the virus has affected over 20million people globally and has inflicted over 7 lac deaths. Nevertheless, the recovery rate is improving with each passing day and over 14 million people have recuperated so far. The statistics indicate that nobody is immune to the disease as the virus continues to spread among all age groups; newborns to the elders, and all compartmentsincluding pregnant women. However, pregnant women may be more susceptible to this infection as they are, in general, highly vulnerable to respiratory infections. There is no evidence for vertical transmission of the COVID-19 virus among pregnant women, but an increased prevalence of preterm deliveries. Besides this, the COVID-19 may alter immune response at the maternal-fetal interface and affect the well-being of mothers as well as infants. Unfortunately, there is limited evidence available in the open literature regarding coronavirus infection during pregnancy and it now appears that certain pregnant women have infected during the present 2019-nCoV pandemic. In this short communication, we study the impact of the COVID-19 infection on vertical transmission and fetal outcome among pregnant women.

scholarly journals Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1457
Author(s):  
Dewald Schoeman ◽  
Burtram C. Fielding
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Antiviral Agents ◽  
The Elderly ◽  
Highly Pathogenic ◽  
Vaccine Responses ◽  
Cell Mediated Immune Response ◽  
Inhibition Antibody ◽  
A Cell ◽  
Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

scholarly journals Neutralizing Antibody Therapeutics for COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 628
Author(s):  
Aeron C. Hurt ◽  
Adam K. Wheatley
Keyword(s):  
High Risk ◽  
Neutralizing Antibodies ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Supplemental Oxygen ◽  
European Medicines Agency ◽  
Global Public Health ◽  
Public Health Burden

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.

scholarly journals An Update on Animal Models for Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Countermeasure Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Zhang ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Haiyan Yang ◽  
Yuefei Jin ◽  
...  
Keyword(s):  
Animal Models ◽  
Severe Acute Respiratory Syndrome ◽  
Research Progress ◽  
Laboratory Mice ◽  
Disease Manifestation ◽  
Highly Pathogenic ◽  
The World ◽  
Coronavirus Infection ◽  
Different Levels ◽  
Critical Aspects

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

scholarly journals Genesis and spread of multiple reassortants during the 2016/2017 H5 avian influenza epidemic in Eurasia

2020 ◽  
Vol 117 (34) ◽  
pp. 20814-20825 ◽  
Author(s):  
Samantha J. Lycett ◽  
Anne Pohlmann ◽  
Christoph Staubach ◽  
Valentina Caliendo ◽  
Mark Woolhouse ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Severe Disease ◽  
Wild Birds ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
Time Resolved ◽  
Bird Populations ◽  
Pathogenic Avian Influenza ◽  
Reassortant Viruses

Highly pathogenic avian influenza (HPAI) viruses of the H5 A/goose/Guangdong/1/96 lineage can cause severe disease in poultry and wild birds, and occasionally in humans. In recent years, H5 HPAI viruses of this lineage infecting poultry in Asia have spilled over into wild birds and spread via bird migration to countries in Europe, Africa, and North America. In 2016/2017, this spillover resulted in the largest HPAI epidemic on record in Europe and was associated with an unusually high frequency of reassortments between H5 HPAI viruses and cocirculating low-pathogenic avian influenza viruses. Here, we show that the seven main H5 reassortant viruses had various combinations of gene segments 1, 2, 3, 5, and 6. Using detailed time-resolved phylogenetic analysis, most of these gene segments likely originated from wild birds and at dates and locations that corresponded to their hosts’ migratory cycles. However, some gene segments in two reassortant viruses likely originated from domestic anseriforms, either in spring 2016 in east China or in autumn 2016 in central Europe. Our results demonstrate that, in addition to domestic anseriforms in Asia, both migratory wild birds and domestic anseriforms in Europe are relevant sources of gene segments for recent reassortant H5 HPAI viruses. The ease with which these H5 HPAI viruses reassort, in combination with repeated spillovers of H5 HPAI viruses into wild birds, increases the risk of emergence of a reassortant virus that persists in wild bird populations yet remains highly pathogenic for poultry.

scholarly journals Emergence and Selection of a Highly Pathogenic Avian Influenza H7N3 Virus

2020 ◽  
Vol 94 (8) ◽  
Author(s):  
Nancy Beerens ◽  
Rene Heutink ◽  
Frank Harders ◽  
Alex Bossers ◽  
Guus Koch ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Cleavage Site ◽  
Highly Pathogenic Avian Influenza ◽  
Severe Disease ◽  
Virus Population ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
High Pathogenicity ◽  
H7n3 Virus ◽  
Selection Of

ABSTRACT Low-pathogenicity avian influenza (LPAI) viruses of subtypes H5 and H7 have the ability to spontaneously mutate to highly pathogenic (HPAI) virus variants, causing high mortality in poultry. The highly pathogenic phenotype is caused by mutation of the hemagglutinin (HA) cleavage site, but additional mutations may play a role. Evidence from the field for the switch to high pathogenicity remains scarce. This study provides direct evidence for LPAI-to-HPAI virus mutation during H7N3 infection of a turkey farm in the Netherlands. No severe clinical symptoms were reported at the farm, but deep sequencing of isolates from the infected turkeys revealed a minority of HPAI virus sequences (0.06%) in the virus population. The HPAI virus contained a 12-nucleotide insertion in the HA cleavage site that was likely introduced by a single event as no intermediates with shorter inserts were identified. This suggests nonhomologous recombination as the mechanism of insertion. Analysis of different organs of the infected turkeys showed the largest amount of HPAI virus in the lung (4.4%). The HPAI virus was rapidly selected in experimentally infected chickens after both intravenous and intranasal/intratracheal inoculation with a mixed virus preparation. Full-genome sequencing revealed that both pathotypes contained a deletion in the stalk region of the neuraminidase protein. We identified additional mutations in HA and polymerase basic protein 1 (PB1) in the HPAI virus, which were already present as minority variants in the LPAI virus population. Our findings provide more insight into the molecular changes and mechanisms involved in the emergence and selection of HPAI viruses. IMPORTANCE Low-pathogenicity avian influenza (LPAI) viruses circulate in wild birds and can be transmitted to poultry. LPAI viruses can mutate to become highly pathogenic avian influenza (HPAI) viruses causing severe disease and death in poultry. Little is known about this switch to high pathogenicity. We isolated an LPAI H7N3 virus from an infected turkey farm and showed that this contains small amounts of HPAI virus. The HPAI virus rapidly outcompeted the LPAI virus in chickens that were experimentally infected with this mixture of viruses. We analyzed the genome sequences of the LPAI and HPAI viruses and identified several changes that may be important for a virus to become highly pathogenic. This knowledge may be used for timely identification of LPAI viruses that pose a risk of becoming highly pathogenic in the field.

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