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

The SARS-CoV-2 spike protein binds and modulates estrogen receptors DOI Creative Commons
Óscar Solís, Andrea R. Beccari, Daniela Iaconis

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(48)

Published: Nov. 30, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme as its primary infection mechanism. Interactions between S and endogenous proteins occur after but are not well understood. We profiled binding of against >9000 human found an interaction estrogen receptor α (ERα). Using bioinformatics, supercomputing, experimental assays, we identified a highly conserved functional nuclear coregulator (NRC) LXD-like motif on the S2 subunit. In cultured cells, DNA transfection increased ERα cytoplasmic accumulation, treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2–infected hamsters localized lung pathology with levels. Postmortem experiments from infected humans confirmed increase colocalization alveolar macrophages. These findings describe discovery S-ERα interaction, imply role for NRC, advance knowledge SARS-CoV-2 biology disease 2019 pathology.

Language: Английский

Citations

32
Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment DOI Creative Commons
Mark C. Chappell

Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1320 - 1337

Published: May 11, 2023

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause death and potentially contributed to a decline life expectancy United States. severe acute respiratory syndrome-related coronavirus-2 binds surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) tissue infection viral replication. ACE2 is important enzymatic component renin-angiotensin system (RAS) expressed lung other organs. regulates levels peptide hormones Ang II Ang-(1–7), which have distinct opposing actions one another, as well cardiovascular peptides. A potential consequence reduced activity by internalization viral-ACE2 complex subsequent activation RAS (higher ratio II:Ang-[1–7]) may exacerbate inflammatory events COVID-19 patients possibly contribute effects long COVID-19. Moreover, present with array autoantibodies various components including II, ACE2, AT 1 Mas receptors. Greater severity also evident male patients, reflect underlying sex differences regulation functional arms RAS. review provides critical evaluation evidence for activated subjects whether this contributes greater males compared females.

Language: Английский

Citations

18
Host Response of Syrian Hamster to SARS-CoV-2 Infection including Differences with Humans and between Sexes DOI Creative Commons

Martina Castellan,

Gianpiero Zamperin, Giulia Franzoni

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 428 - 428

Published: Feb. 3, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the importance having proper tools and models to study pathophysiology emerging infectious diseases test therapeutic protocols, assess changes in viral phenotypes, evaluate effects evolution. This provided a comprehensive characterization Syrian hamster (Mesocricetus auratus) as an animal model for SARS-CoV-2 infection using different approaches (description clinical signs, load, receptor profiling, host immune response) targeting four organs (lungs, intestine, brain, PBMCs). Our data showed that both male female hamsters were susceptible developed disease similar one observed patients with COVID-19 included moderate pulmonary lesions, inflammation, recruitment system lungs at systemic level. However, all animals recovered within 14 days without developing pathology seen humans, none them died. We found faint evidence intestinal neurological tropism associated absence lesions minimal response intestines brains, which another crucial difference multiorgan impairment COVID-19. When comparing hamsters, we males sustained higher RNA shedding replication lungs, suffered from more symptoms histopathological triggered inflammation. Overall, these confirmed suitable mild reflected sex-related differences against virus humans.

Language: Английский

Citations

17
The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization DOI Creative Commons
Amy B. Karger, James D. Brien,

Jayne M. Christen

et al.

mSphere, Journal Year: 2022, Volume and Issue: 7(4)

Published: June 15, 2022

SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these using reference materials establish standardized reporting units. This will facilitate clinical interpretation of serology results cross-comparison research data.

Language: Английский

Citations

23
Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model DOI Creative Commons

Devanshi R. Patel,

Allen M. Minns,

Derek G. Sim

et al.

Microbiology Spectrum, Journal Year: 2024, Volume and Issue: 12(3)

Published: Feb. 9, 2024

ABSTRACT Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these reduce disease severity, they do not prevent infection. To infection limit transmission, must be that induce immunity in the tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The candidate consisted of self-assembling 60-subunit I3-01 protein scaffold covalently decorated SARS-CoV-2 receptor-binding domain (RBD) using SpyCatcher-SpyTag system. We verified intended antigen display features by reconstructing to 3.4 A cryogenicelectron microscopy. Using this RBD-grafted SpyCage (RBD + SpyCage), two vaccination “gold-standard” pre-clinical Syrian hamster model. initial study focused on assessing immunogenicity RBD combined LTA1 adjuvant. These showed induced antibody response promoted viral clearance but did Inclusion adjuvant enhanced magnitude enhance protection. Thus, expanded study, absence adjuvant, evaluated if covalent bonding was required response. Covalent grafting immunogenic, animals vaccinated more rapidly cleared from both upper lower findings demonstrate platform can protection and, additional modifications improve immunogenicity, is a versatile development targeting pathogens. IMPORTANCE Despite availability efficacious COVID continues spread. next generation mucosa proof-of-principle, recombinant scaffold, SpyCage, S (SpyCage RBD). show immunogenic nose lungs hamsters. Moreover, immune when given via route. proof-of-concept indicate further enhancements (e.g., incorporation optimization), has potential as versatile,

Language: Английский

Citations

6
Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response? DOI Creative Commons

Alexandros Popotas,

Georges Casimir, Francis Corazza

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 21, 2024

An increasing number of studies have highlighted the existence a sex-specific immune response, wherein men experience worse prognosis in cases acute inflammatory diseases. Initially, this sex-dependent response was attributed to influence sex hormones. However, growing body evidence has shifted focus toward chromosomes rather than hormones shaping these disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated pathways been implicated driving response. These are encoded by genes located on X chromosome. TLRs pivotal components innate system, playing crucial roles responding infectious diseases, including bacterial viral pathogens, well trauma-related conditions. Importantly, TLR-mediated responses, indicated production specific proteins cytokines, exhibit discernible patterns. In review, we delve into subject bias TLR activation explore its clinical implications relatively both chromosome hormonal environment. The overarching objective is enhance our understanding fundamental mechanisms underlying differences.

Language: Английский

Citations

6
Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters DOI Creative Commons
Kathleen R. Mulka, Sarah E. Beck,

Clarisse V. Solis

et al.

American Journal Of Pathology, Journal Year: 2021, Volume and Issue: 192(2), P. 195 - 207

Published: Nov. 10, 2021

Language: Английский

Citations

28
After the virus has cleared—Can preclinical models be employed for Long COVID research? DOI Creative Commons
Ethan B. Jansen,

Spencer N. Orvold,

Cynthia L. Swan

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(9), P. e1010741 - e1010741

Published: Sept. 7, 2022

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) can cause the life-threatening acute respiratory disease called COVID-19 (Coronavirus Disease 2019) as well debilitating multiorgan dysfunction that persists after initial viral phase has resolved. Long COVID or Post-Acute Sequelae of (PASC) is manifested by a variety symptoms, including fatigue, dyspnea, arthralgia, myalgia, heart palpitations, and memory issues sometimes affecting between 30% 75% recovering patients. However, little known about mechanisms causing there are no widely accepted treatments therapeutics. After introducing clinical aspects in humans, we summarize work animals (mice, Syrian hamsters, ferrets, nonhuman primates (NHPs)) to model human COVID-19. The virology, pathology, immune responses, involvement explored. Additionally, any studies investigating time points longer than 14 days post infection (pi) highlighted for insight into possible long-term characteristics. Finally, discuss how models be leveraged treatment evaluation, pharmacological agents currently trials treating COVID. establishment recognized preclinical representing condition would allow identification serve vehicle evaluating potential

Language: Английский

Citations

20
Spike-protein proteolytic antibodies in COVID-19 convalescent plasma contribute to SARS-CoV-2 neutralization DOI Creative Commons
Scott A. McConnell,

Jaiprasath Sachithanandham,

Nathan J. Mudrak

et al.

Cell chemical biology, Journal Year: 2023, Volume and Issue: 30(7), P. 726 - 738.e4

Published: June 25, 2023

Language: Английский

Citations

13
Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells DOI Creative Commons
Alok Kumar Singh, Rulin Wang, Kara A. Lombardo

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107733 - 107733

Published: Aug. 24, 2023

Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination COVID-19 using the golden Syrian hamster model. conferred a modest reduction on lung SCV2 load, bronchopneumonia scores, weight loss, accompanied by reversal of SCV2-mediated T cell lymphopenia, reduced granulocytes. uniquely recruited immunoglobulin-producing plasma cells to suggesting accelerated local antibody production. also elevated levels Th1, Th17, Treg, CTLs, Tmem cells, with transcriptional shift away from exhaustion markers toward antigen presentation repair. Similarly, enhanced recruitment alveolar macrophages key interstitial macrophage subsets, that show IFN-associated gene expression. Our observations indicate protects immunopathology promoting early immunoglobulin production immunotolerizing patterns among myeloid lymphoid populations.

Language: Английский

Citations

11