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23 results on '"Pinski, Amanda N."'

1. Differential dynamics of peripheral immune responses to acute SARS-CoV-2 infection in older adults

Author

Lewis, Sloan A, Sureshchandra, Suhas, Zulu, Michael Z, Doratt, Brianna, Jankeel, Allen, Ibraim, Izabela Coimbra, Pinski, Amanda N, Rhoades, Nicholas S, Curtis, Micaila, Jiang, Xiwen, Tifrea, Delia, Zaldivar, Frank, Shen, Weining, Edwards, Robert A, Chow, Daniel, Cooper, Dan, Amin, Alpesh, and Messaoudi, Ilhem

Subjects
Biomedical and Clinical Sciences, Immunology, Aging, Infectious Diseases, Clinical Research, Vaccine Related, Emerging Infectious Diseases, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, Humans, Leukocytes, Mononuclear, COVID-19, SARS-CoV-2, Acclimatization, Immunity, Clinical sciences
Abstract

In this study, peripheral blood mononuclear cells from young and old patients with COVID-19 were examined phenotypically, transcriptionally and functionally to reveal age-, time- and severity-specific adaptations. Gene signatures within memory B cells and plasmablasts correlated with reduced frequency of antigen-specific B cells and neutralizing antibodies in older patients with severe COVID-19. Moreover, these patients exhibited exacerbated T cell lymphopenia, which correlated with lower plasma interleukin-2, and diminished antigen-specific T cell responses. Single-cell RNA sequencing revealed augmented signatures of activation, exhaustion, cytotoxicity and type I interferon signaling in memory T and natural killer cells with age. Although cytokine storm was evident in both age groups, older individuals exhibited elevated levels of myeloid cell recruiting factors. Furthermore, we observed redistribution of monocyte and dendritic cell subsets and emergence of a suppressive phenotype with severe disease, which was reversed only in young patients over time. This analysis provides new insights into the impact of aging on COVID-19.

Published
2021

2. Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients

Author

Zulu, Michael Z, Sureshchandra, Suhas, Pinski, Amanda N, Doratt, Brianna, Shen, Weining, and Messaoudi, Ilhem

Subjects
Biomedical and Clinical Sciences, Immunology, Emerging Infectious Diseases, Clinical Research, Pneumonia & Influenza, Prevention, Aging, Nutrition, Infectious Diseases, Lung, Pneumonia, Vaccine Related, Obesity, Biodefense, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Adaptive Immunity, Adult, Aged, Aged, 80 and over, Antibodies, Viral, Body Mass Index, COVID-19, Cytokines, Female, Hospitalization, Humans, Immunity, Innate, Linear Models, Male, Middle Aged, Monocytes, SARS-CoV-2, Young Adult, obesity, aging, innate immunity, monocytes, cytokines, Medical Microbiology, Biochemistry and cell biology, Genetics
Abstract

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.

Published
2021

8. Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine

Author

Furuyama, Wakako, primary, Shifflett, Kyle, additional, Pinski, Amanda N., additional, Griffin, Amanda J., additional, Feldmann, Friederike, additional, Okumura, Atsushi, additional, Gourdine, Tylisha, additional, Jankeel, Allen, additional, Lovaglio, Jamie, additional, Hanley, Patrick W., additional, Thomas, Tina, additional, Clancy, Chad S., additional, Messaoudi, Ilhem, additional, O’Donnell, Kyle L., additional, and Marzi, Andrea, additional

Published
2022
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10. Corticosteroid treatment in COVID-19 modulates host inflammatory responses and transcriptional signatures of immune dysregulation

Author

Pinski, Amanda N, primary, Steffen, Tara L, additional, Zulu, Michael Z, additional, George, Sarah L, additional, Dickson, Alexandria, additional, Tifrea, Delia, additional, Maroney, Kevin J, additional, Tedeschi, Neil, additional, Zhang, Yun, additional, Scheuermann, Richard H, additional, Pinto, Amelia K, additional, Brien, James D, additional, and Messaoudi, Ilhem, additional

Published
2021
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19. Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine

Author

Furuyama, Wakako, primary, Shifflett, Kyle, additional, Pinski, Amanda N., additional, Griffin, Amanda J., additional, Feldmann, Friederike, additional, Okumura, Atsushi, additional, Gourdine, Tylisha, additional, Jankeel, Allen, additional, Lovaglio, Jamie, additional, Hanley, Patrick W., additional, Thomas, Tina, additional, Clancy, Chad S., additional, Messaoudi, Ilhem, additional, O’Donnell, Kyle L., additional, and Marzi, Andrea, additional

Published
2021
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21. Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosain the nose

Author

Rhoades, Nicholas S., Pinski, Amanda N., Monsibais, Alisha N., Jankeel, Allen, Doratt, Brianna M., Cinco, Isaac R., Ibraim, Izabela, and Messaoudi, Ilhem

Abstract

Research conducted on SARS-CoV-2 pathogenesis and COVID-19 has focused on the systemic host response, especially that generated by severely ill patients with few studies investigating the impact of acute SARS-CoV-2 at the site of infection. We show that the nasal microbiome of SARS-CoV-2 positive patients (CoV+, n=68) at the time of diagnosis was unique compared to CoV- healthcare workers (n=45) and CoV- outpatients (n=21). This shift was marked by an increased abundance of bacterial pathogens including Pseudomonas aeruginosawhich was also positively associated with viral RNA load. Additionally, we observed a robust host transcriptional response in the nasal epithelia of CoV+ patients, indicative of an antiviral innate immune repones and neuronal damage. These data suggest that the inflammatory response caused by SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections.

Published
2021
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22. Pathogenic and transcriptomic differences of emerging SARS-CoV-2 variants in the Syrian golden hamster model.

Author

O'Donnell KL, Pinski AN, Clancy CS, Gourdine T, Shifflett K, Fletcher P, Messaoudi I, and Marzi A

Abstract

Following the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid spread throughout the world, new viral variants of concern (VOC) have emerged. There is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. Syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (COVID-19). In this study, we show that intranasal inoculation of SARS-CoV-2 into hamsters with the ancestral virus (nCoV-WA1-2020) or VOC first identified in the United Kingdom (B.1.1.7) and South Africa (B.1.351) led to similar gross and histopathologic pulmonary lesions. Although differences in viral genomic copy numbers were noted in the lungs and oral swabs of challenged animals, infectious titers in the lungs were comparable. Antibody neutralization capacities varied, dependent on the original challenge virus and cross-variant protective capacity. Transcriptional profiling indicated significant induction of antiviral pathways in response to all three challenges with a more robust inflammatory signature in response to B.1.1.7. Furthermore, no additional mutations in the spike protein were detected at peak disease. In conclusion, the emerging VOC showed distinct humoral responses and transcriptional profiles in the hamster model compared to the ancestral virus.

Published
2021
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23. Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine.

Author

Furuyama W, Shifflett K, Pinski AN, Griffin AJ, Feldmann F, Okumura A, Gourdine T, Jankeel A, Lovaglio J, Hanley PW, Thomas T, Clancy CS, Messaoudi I, O'Donnell KL, and Marzi A

Abstract

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (IN) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study., One Sentence Summary: VSV vaccine protects NHPs from COVID-19 in 10 days.

Published
2021
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