Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19 DOI Creative Commons
Abigail Vanderheiden, Michael Diamond

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 98 - 98

Published: Jan. 14, 2025

Post-acute sequelae of COVID-19 (PASC) are a diverse set symptoms and syndromes driven by dysfunction multiple organ systems that can persist for years negatively impact the quality life millions individuals. We currently lack specific therapeutics patients with PASC, due in part to an incomplete understanding its pathogenesis, especially non-pulmonary sequelae. Here, we discuss three animal models have been utilized investigate PASC: non-human primates (NHPs), hamsters, mice. focus on neurological, gastrointestinal, cardiovascular PASC highlight advances mechanistic insight made using these models, as well discussing warrant continued intensive research.

Language: Английский

A bacterial extracellular vesicle‐based intranasal vaccine against SARS‐CoV‐2 protects against disease and elicits neutralizing antibodies to wild‐type and Delta variants DOI
Linglei Jiang, Tom A. P. Driedonks, Wouter S. P. Jong

et al.

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(3)

Published: March 1, 2022

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Current SARS-CoV-2 include mRNA-containing lipid nanoparticles or adenoviral vectors that encode Spike (S) protein of SARS-CoV-2, inactivated virus, subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed future address issues such as stability and storage requirements, need for vaccine boosters, desirability different routes administration, emergence variants Delta variant. Here, we present a novel, well-characterized candidate based on extracellular vesicles (EVs) Salmonella typhimurium are decorated with mammalian cell culture-derived receptor-binding domain (RBD). RBD-conjugated outer membrane (RBD-OMVs) were used immunize golden Syrian hamster (Mesocricetus auratus) model COVID-19. Intranasal immunization resulted high titres blood anti-RBD IgG well detectable mucosal responses. Neutralizing antibody activity against wild-type was evident all vaccinated subjects. Upon challenge live hamsters immunized RBD-OMV, but not animals unconjugated OMVs vehicle control, avoided body mass loss, had lower virus bronchoalveolar lavage fluid, experienced less lung pathology. Our results emphasize value versatility OMV-based approaches.

Language: Английский

Citations

119
Animal models for COVID-19: advances, gaps and perspectives DOI Creative Commons
Changfa Fan, Yong Wu,

Rui Xiong

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 7, 2022

Abstract COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since outbreak in late 2019, animal models have been playing crucial roles aiding rapid development vaccines/drugs for prevention and therapy, as well understanding pathogenesis SARS-CoV-2 infection immune responses hosts. However, current some deficits there an urgent need novel to evaluate virulence variants concerns (VOC), antibody-dependent enhancement (ADE), various comorbidities COVID-19. This review summarizes clinical features COVID-19 different populations, characteristics major including those naturally susceptible animals, such non-human primates, Syrian hamster, ferret, minks, poultry, livestock, mouse sensitized genetically modified, AAV/adenoviral transduced, mouse-adapted strain engraftment human tissues or cells. host receptors proteases essential designing advanced modified models, successful studies on are also reviewed. Several improved alternatives future proposed, reselection alternative receptor genes multiple gene combinations, use transgenic knock-in method, strains establishing next generation mice.

Language: Английский

Citations

84
SARS-CoV-2 Infection Induces Ferroptosis of Sinoatrial Node Pacemaker Cells DOI Open Access
Yuling Han, Jiajun Zhu, Liuliu Yang

et al.

Circulation Research, Journal Year: 2022, Volume and Issue: 130(7), P. 963 - 977

Published: March 8, 2022

Increasing evidence suggests that cardiac arrhythmias are frequent clinical features of coronavirus disease 2019 (COVID-19). Sinus node damage may lead to bradycardia. However, it is challenging explore human sinoatrial (SAN) pathophysiology due difficulty in isolating and culturing SAN cells. Embryonic stem cells (ESCs) can be a source derive SAN-like pacemaker for modeling.

Language: Английский

Citations

80
Advances and gaps in SARS-CoV-2 infection models DOI Creative Commons
César Muñoz‐Fontela, Lina Widerspick, Randy A. Albrecht

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(1), P. e1010161 - e1010161

Published: Jan. 13, 2022

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants concern (VOCs). Preclinical models disease, in particular animal models, are essential investigate VOC pathogenesis, correlates protection postexposure therapies. Here, we provide an update from World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances preclinical models. In particular, discuss how model research playing a key role evaluate virulence, transmission immune escape, being refined recapitulate demographic variables comorbidities age.

Language: Английский

Citations

79
Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice DOI Creative Commons
Alvaro A. Ordoñez, C. Korin Bullen, A.F. Villabona-Rueda

et al.

Communications Biology, Journal Year: 2022, Volume and Issue: 5(1)

Published: March 18, 2022

Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are limited therapeutic options for prevention and treatment SARS-CoV-2 infections. We evaluated antiviral activity sulforaphane (SFN), principal biologically active phytochemical derived from glucoraphanin, naturally occurring precursor present in high concentrations cruciferous vegetables. SFN inhibited vitro replication six strains SARS-CoV-2, including Delta Omicron, as well that seasonal HCoV-OC43. Further, remdesivir interacted synergistically to inhibit infection vitro. Prophylactic administration K18-hACE2 mice prior intranasal significantly decreased viral load lungs upper respiratory tract reduced lung injury pulmonary pathology compared untreated infected mice. diminished immune cell activation lungs, lower recruitment myeloid cells reduction T cytokine production. Our results suggest should be explored potential agent or

Language: Английский

Citations

71
Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants DOI Creative Commons

Mengfei Chen,

Andrew Pekosz,

Jason Villano

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(8)

Published: March 14, 2024

SARS-CoV-2 infection of the upper airway and subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying human biopsies vitro a hamster model vivo, we demonstrated transition nasal tropism from olfactory to respiratory epithelium as virus evolved. Analyzing each variant revealed that WA1 or Delta infect proportion neurons addition primary target sustentacular cells. The possessed broader cellular invasion capacity into submucosa, while Omicron displayed enhanced longer retention sinonasal epithelium. neuronal by bulb transport via axon were more pronounced younger hosts. In addition, observed viral clearance delay phagocytic dysfunction aged mucosa accompanied decline phagocytosis related genes. Furthermore, robust basal stem cell activation contributed neuroepithelial regeneration restores ACE2 expression post-infection. Together, our study characterized strains, clearance, post infection. shifting characteristics at portal provides insight variability clinical features, particularly long COVID, may suggest differing strategies for early local intervention.

Language: Английский

Citations

17
Hamster models of COVID-19 pneumonia reviewed: How human can they be? DOI Creative Commons
Achim D. Gruber, Theresa C. Firsching, Jakob Trimpert

et al.

Veterinary Pathology, Journal Year: 2021, Volume and Issue: 59(4), P. 528 - 545

Published: Dec. 2, 2021

The dramatic global consequences of the coronavirus disease 2019 (COVID-19) pandemic soon fueled quests for a suitable model that would facilitate development and testing therapies vaccines. In contrast to other rodents, hamsters are naturally susceptible infection with severe acute respiratory syndrome 2 (SARS-CoV-2), Syrian hamster ( Mesocricetus auratus) rapidly developed into popular model. It recapitulates many characteristic features as seen in patients moderate, self-limiting course such specific patterns tract inflammation, vascular endothelialitis, age dependence. Among 4 species examined, Roborovski dwarf Phodopus roborovskii) more closely mimics highly frequent lethal outcome, including devastating diffuse alveolar damage coagulopathy. Thus, different available mimic courses wide spectrum COVID-19 manifestations humans. On hand, fewer diagnostic tools information on immune functions molecular pathways than mice, which limits mechanistic studies inference humans several aspects. Still, under conditions high pressure progress both basic clinically oriented research, has turned leading non-transgenic at an unprecedented pace, currently used innumerable all aim combat impact virus its new variants concern. As models, strength rests upon solid understanding similarities differences from human disease, we review here.

Language: Английский

Citations

68
Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS‐CoV‐2 infection* DOI
Salma Sheikh‐Mohamed, Erin C. Sanders, Jennifer L. Gommerman

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 309(1), P. 75 - 85

Published: July 11, 2022

Abstract In early 2020, a global emergency was upon us in the form of coronavirus disease 2019 (COVID‐19) pandemic. While horrific its health, social and economic devastation, one silver lining to this crisis has been rapid mobilization cross‐institute, even cross‐country teams that shared common goals learning as much we could quickly possible about novel severe acute respiratory syndrome 2 (SARS‐CoV‐2) how immune system would respond both virus COVID‐19 vaccines. Many these were formed by women who realized classical model “publish first at all costs” maladaptive for circumstances needed be supplanted more collaborative solution‐focused approach. This review is an example collaboration unfolded separate countries, Canada United States, then also Israel. Not only did allow cross‐validate our results using different hands/techniques/samples, but it took advantage vaccine types schedules rolled out respective home countries. The result new understanding mucosal immunity SARS‐CoV‐2 infection vs vaccination can measured saliva biofluid, what vaccines are best able induce (limited) immunity, potential correlates protection against breakthrough infection. review, will share have learned response provide perspective on may required next‐generation pan‐sarbecoronavirus approaches.

Language: Английский

Citations

48
Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control DOI Creative Commons
Shen Wang, Wujian Li,

Zhenshan Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 11, 2024

Language: Английский

Citations

10
Infectious SARS-CoV-2 Is Emitted in Aerosol Particles DOI Creative Commons
Seth A. Hawks, Aaron J. Prussin, Sarah C. Kuchinsky

et al.

mBio, Journal Year: 2021, Volume and Issue: 12(5)

Published: Oct. 19, 2021

SARS-CoV-2 is a respiratory virus and has been isolated from the air near COVID-19 patients. Here, using hamster model of infection, we demonstrate that emitted in aerosol particles prior to concurrent with onset mild disease.

Language: Английский

Citations

51