Dataset Information

Neutrophil and monocyte dysfunctional effector response towards bacterial challenge in critically ill COVID-19 patients

ABSTRACT: In this study, we aim to evaluate the relation between COVID-19 and bacterial secondary superinfections. We assessed the functional responses of neutrophils and monocytes isolated from acute and recovery COVID-19 patients upon bacterial infection using Flow-cytometry and proteomics based assays. Both neutrophils and monocytes showed impared intracellular microbicidal capacity along with a decreased functional response. Determination of plasma cytokines levels showed a significant association of certain cytokines towards secondary bacterial infection.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Covid-19

SUBMITTER: Alejandro Gomez Mejia

LAB HEAD: Annelies S. Zinkernagel

PROVIDER: PXD029547 | Pride | 2021-12-10

REPOSITORIES: Pride

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Publications

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19.

Mairpady Shambat Srikanth S Gómez-Mejia Alejandro A Schweizer Tiziano A TA Huemer Markus M Chang Chun-Chi CC Acevedo Claudio C Bergada-Pijuan Judith J Vulin Clément C Hofmaenner Daniel A DA Scheier Thomas C TC Hertegonne Sanne S Parietti Elena E Miroshnikova Nataliya N Wendel Garcia Pedro D PD Hilty Matthias P MP Buehler Philipp Karl PK Schuepbach Reto A RA Brugger Silvio D SD Zinkernagel Annelies S AS

PLoS pathogens 20220110 1

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hype ...[more]

PMID: 35007290

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Project description:SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNAseq atlas that is freely accessible (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils and a greater degree of steroid-induced immature neutrophil expansion. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined. The identified molecular pathways can now be targeted to develop improved therapeutics.

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