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A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections.

ABSTRACT: Despite recent studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), little is known about how the immune response against SARS-CoV-2 differs from other respiratory infections. We compare the immune signature from hospitalized SARS-CoV-2–infected patients to patients hospitalized prepandemic with influenza or respiratory syncytial virus (RSV). Our in-depth profiling indicates that the immune landscape in SARS-CoV-2 patients is largely similar to flu or RSV patients. Unique to patients infected with SARS-CoV-2 who had the most critical clinical disease were changes in the regulatory T cell (T_reg) compartment. A T_reg signature including increased frequency, activation status, and migration markers was correlated COVID-19 severity. These findings are relevant as T_regs are considered for therapy to combat the severe inflammation seen in COVID-19 patients. Likewise, having defined the overlapping immune landscapes in SARS-CoV-2, existing knowledge of flu and RSV infections could be leveraged to identify common treatment strategies.

SUBMITTER: Vick SC

PROVIDER: S-EPMC8580318 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections.

Vick Sarah C SC Frutoso Marie M Mair Florian F Konecny Andrew J AJ Greene Evan E Wolf Caitlin R CR Logue Jennifer K JK Franko Nicholas M NM Boonyaratanakornkit Jim J Gottardo Raphael R Schiffer Joshua T JT Chu Helen Y HY Prlic Martin M Lund Jennifer M JM

Science advances 20211110 46

Despite recent studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), little is known about how the immune response against SARS-CoV-2 differs from other respiratory infections. We compare the immune signature from hospitalized SARS-CoV-2–infected patients to patients hospitalized prepandemic with influenza or respiratory syncytial virus (RSV). Our in-depth profiling indicates that the immune landscape in SARS-CoV-2 patients is largely similar to flu or RSV patients ...[more]

PMID: 34757794

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Project description:SARS-CoV-2 infection has caused a lasting global pandemic costing millions of lives and untold additional costs. Understanding the immune response to SARS-CoV-2 has been one of the main challenges in the past year in order to decipher mechanisms of host responses and interpret disease pathogenesis. Comparatively little is known in regard to how the immune response against SARS-CoV-2 differs from other respiratory infections. In our study, we compare the peripheral blood immune signature from SARS-CoV-2 infected patients to patients hospitalized pre-pandemic with Influenza Virus or Respiratory Syncytial Virus (RSV). Our in-depth profiling indicates that the immune landscape in patients infected by SARS-CoV-2 is largely similar to patients hospitalized with Flu or RSV. Similarly, serum cytokine and chemokine expression patterns were largely overlapping. Unique to patients infected with SARS-CoV-2 who had the most critical clinical disease state were changes in the regulatory T cell (Treg) compartment. A Treg signature including increased frequency, activation status, and migration markers was correlated with the severity of COVID-19 disease. These findings are particularly relevant as Tregs are being discussed as a therapy to combat the severe inflammation seen in COVID-19 patients. Likewise, having defined the overlapping immune landscapes in SARS-CoV-2, existing knowledge of Flu and RSV infections could be leveraged to identify common treatment strategies.HighlightsThe immune landscapes of hospitalized pre-pandemic RSV and influenza patients are similar to SARS-CoV-2 patientsSerum cytokine and chemokine expression patterns are largely similar between patients hospitalized with respiratory virus infections, including SARS-CoV-2, versus healthy donorsSARS-CoV-2 patients with the most critical disease displayed unique changes in the Treg compartmentadvances in understanding and treating SARS-CoV-2 could be leveraged for other common respiratory infections.

Project description:IntroductionInfection with SARS-CoV-2 leads to coronavirus disease 2019 (COVID-19), which can result in acute respiratory distress syndrome and multiple organ failure. However, its comprehensive influence on pathological immune responses in the respiratory epithelium and peripheral immune cells is not yet fully understood.MethodsIn this study, we analyzed multiple public scRNA-seq datasets of nasopharyngeal swabs and peripheral blood to investigate the gene regulatory networks (GRNs) of healthy individuals and COVID-19 patients with mild/moderate and severe disease, respectively. Cell-cell communication networks among cell types were also inferred. Finally, validations were conducted using bulk RNA-seq and proteome data.ResultsSimilar and dissimilar regulons were identified within or between epithelial and immune cells during COVID-19 severity progression. The relative transcription factors (TFs) and their targets were used to construct GRNs among different infection sites and conditions. Between respiratory epithelial and peripheral immune cells, different TFs tended to be used to regulate the activity of a cell between healthy individuals and COVID-19 patients, although they had some TFs in common. For example, XBP1, FOS, STAT1, and STAT2 were activated in both the epithelial and immune cells of virus-infected individuals. In contrast, severe COVID-19 cases exhibited activation of CEBPD in peripheral immune cells, while CEBPB was exclusively activated in respiratory epithelial cells. Moreover, in patients with severe COVID-19, although some inflammatory genes, such as S100A8/A9, were found to be upregulated in both respiratory epithelial and peripheral immune cells, their relative regulators can differ in terms of cell types. The cell-cell communication analysis suggested that epidermal growth factor receptor signaling among epithelia contributes to mild/moderate disease, and chemokine signaling among immune cells contributes to severe disease.ConclusionThis study identified cell type- and condition-specific regulons in a wide range of cell types from the initial infection site to the peripheral blood, and clarified the diverse mechanisms of maladaptive responses to SARS-CoV-2 infection.

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A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections.

Publications

A regulatory T cell signature distinguishes the immune landscape of COVID-19 patients from those with other respiratory infections.

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