Longitudinal Assessment of Anti-SARS-CoV-2 Immune Responses for Six Months Based on the Clinical Severity of COVID-19

Background: The overall performance of a multiple component vaccine assessed by the vaccine-elicited immune responses across various strains in a repeated vaccination setting has not been well-studied, and the comparison between adults and teenagers is yet to be made.Methods: A human cohort study was conducted at the University of Georgia, with 140 subjects (86 adults and 54 teenagers) repeatedly vaccinated in the 2017/2018 and 2018/2019 influenza seasons. Host information was prospectively collected, and serum samples were collected before and after vaccination in each season. The association between host factors and repeated measures of hemagglutination inhibition (HAI) composite scores was assessed by generalized linear models with generalized estimating equations.Results: The mean HAI composite scores for the entire sample (t = 4.26, df = 139, p < 0.001) and the teenager group (t = 6.44, df = 53, p < 0.001) declined in the second season, while the changes in the adults were not statistically significant (t = −1.14, df = 85, p = 0.26). A mixture pattern of changes in both directions was observed in the adults when stratified by prior vaccination. In addition, the regression analysis suggested an interactive effect of age and BMI on the HAI composite scores in the overall population (beta = 0.005; 95% CI, 0.0008–0.01) and the adults (beta = 0.005; 95% CI, 0.0005–0.01).Conclusions: Our study found distinct vaccine-elicited immune responses between adults and teenagers when both were repeatedly vaccinated in consecutive years. An interactive effect of age and BMI on the HAI composite scores were identified in the overall population and the adults.

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Kynurenic acid underlies sex-specific immune responses to COVID-19

10.1101/2020.09.06.20189159 ◽

2020 ◽

Author(s):

Yuping Cai ◽

Daniel J Kim ◽

Takehiro Takahashi ◽

David I Broadhurst ◽

Shuangge Ma ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Clinical Outcomes ◽

Kynurenic Acid ◽

Glutamate Release ◽

T Cell Responses ◽

Tissue Expression ◽

Receptor Activation ◽

Clinical Severity ◽

Cell Responses

Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.

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Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses

Journal of Virology ◽

10.1128/jvi.01523-15 ◽

2015 ◽

Vol 89 (20) ◽

pp. 10190-10205 ◽

Cited By ~ 20

Author(s):

Boris M. Hartmann ◽

Juilee Thakar ◽

Randy A. Albrecht ◽

Stefan Avey ◽

Elena Zaslavsky ◽

...

Keyword(s):

Immune Responses ◽

Human Health ◽

New Caledonia ◽

H1n1 Influenza ◽

Influenza Viruses ◽

Antigenic Drift ◽

Clinical Severity ◽

Time Shift ◽

Specific Response ◽

Transcriptional Responses

ABSTRACTInfluenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-κB following infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss.IMPORTANCEContinuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-κB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses.

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Identification of biomarkers associated with clinical severity of chronic obstructive pulmonary disease

PeerJ ◽

10.7717/peerj.10513 ◽

2020 ◽

Vol 8 ◽

pp. e10513

Author(s):

Jie Zhang ◽

Changli Zhu ◽

Hong Gao ◽

Xun Liang ◽

Xiaoqian Fan ◽

...

Keyword(s):

Gene Expression ◽

Immune Responses ◽

Inflammatory Responses ◽

Lymphocyte Activation ◽

Stage I ◽

Clinical Severity ◽

Chronic Obstructive ◽

Clinical Classification ◽

Obstructive Pulmonary Disease ◽

Blood Samples

We sought to identify the biomarkers related to the clinical severity of stage I to stage IV chronic obstructive pulmonary disease (COPD). Gene expression profiles from the blood samples of COPD patients at each of the four stages were acquired from the Gene Expression Omnibus Database (GEO, accession number: GSE54837). Genes showing expression changes among the different stages were sorted by soft clustering. We performed functional enrichment, protein–protein interaction (PPI), and miRNA regulatory network analyses for the differentially expressed genes. The biomarkers associated with the clinical classification of COPD were selected from logistic regression models and the relationships between TLR2 and inflammatory factors were verified in clinical blood samples by qPCR and ELISA. Gene clusters demonstrating continuously rising or falling changes in expression (clusters 1, 2, and 7 and clusters 5, 6, and 8, respectively) from stage I to IV were defined as upregulated and downregulated genes, respectively, and further analyzed. The upregulated genes were enriched in functions associated with defense, inflammatory, or immune responses. The downregulated genes were associated with lymphocyte activation and cell activation. TLR2, HMOX1, and CD79A were hub proteins in the integrated network of PPI and miRNA regulatory networks. TLR2 and CD79A were significantly correlated with clinical classifications. TLR2 was closely associated with inflammatory responses during COPD progression. Functions associated with inflammatory and immune responses as well as lymphocyte activation may play important roles in the progression of COPD from stage I to IV. TLR2 and CD79A may serve as potential biomarkers for the clinical severity of COPD. TLR2 and CD79A may also serve as independent biomarkers in the clinical classification in COPD. TLR2 may play an important role in the inflammatory responses of COPD.

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Collective Clustering Dynamics of SARS-COV-2 Particles

10.20944/preprints202004.0296.v1 ◽

2020 ◽

Author(s):

Arturo Tozzi ◽

James F. Peters ◽

Isabella Annesi-Maesano ◽

Gennaro D'Amato

Keyword(s):

Immune Responses ◽

Cultured Cells ◽

Therapeutic Strategies ◽

Clinical Severity ◽

Host Cells ◽

Beneficial Effects ◽

Viral Particles ◽

Novel Therapeutic Strategies ◽

Clustering Dynamics ◽

Clustering Behavior

Collective spread of aggregated viral particles may have beneficial effects on viral capability to survive in the external environment, to counteract immune responses, and to successfully colonize host cells. Here we ask whether SARS-Cov-2 particles, responsible for COVID-19, display collective clustering behavior. Looking at microphotographs and movies of SARS-Cov-2 particles emerging from the surface of cultured cells, we describe single virions that tend to aggregate in progressively larger globular assemblies, until a network-like appearance is achieved. When SARS-Cov-2 particles stick into each other, the squeezing of single virions leads to improved viral package in host’s fluids. We discuss how these findings might explain both the ability to spread of SARS-Cov-2 and the clinical severity of COVID-19 in humans, paving the way to novel therapeutic strategies to mechanically disrupt collective clustering.

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Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease

Viruses ◽

10.3390/v13081597 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1597

Author(s):

Peter Simons ◽

Yan Guo ◽

Virginie Bondu ◽

Susan L. Tigert ◽

Michelle Harkins ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Plasminogen Activator ◽

Case Fatality ◽

Principal Component ◽

Longitudinal Assessment ◽

Plasminogen Activator Inhibitor 1 ◽

T Helper 17 ◽

End Stage ◽

Pai 1

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors’ and decedents’ cases. However, total uPA in decedents’ cases was significantly higher compared to survivors’. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.

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