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Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.


ABSTRACT: Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.

SUBMITTER: Schimke LF 

PROVIDER: S-EPMC8909161 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Severe COVID-19 Shares a Common Neutrophil Activation Signature with Other Acute Inflammatory States.

Schimke Lena F LF   Marques Alexandre H C AHC   Baiocchi Gabriela Crispim GC   de Souza Prado Caroline Aliane CA   Fonseca Dennyson Leandro M DLM   Freire Paula Paccielli PP   Rodrigues Plaça Desirée D   Salerno Filgueiras Igor I   Coelho Salgado Ranieri R   Jansen-Marques Gabriel G   Rocha Oliveira Antonio Edson AE   Peron Jean Pierre Schatzmann JPS   Cabral-Miranda Gustavo G   Barbuto José Alexandre Marzagão JAM   Camara Niels Olsen Saraiva NOS   Calich Vera Lúcia Garcia VLG   Ochs Hans D HD   Condino-Neto Antonio A   Overmyer Katherine A KA   Coon Joshua J JJ   Balnis Joseph J   Jaitovich Ariel A   Schulte-Schrepping Jonas J   Ulas Thomas T   Schultze Joachim L JL   Nakaya Helder I HI   Jurisica Igor I   Cabral-Marques Otávio O  

Cells 20220301 5


Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respi  ...[more]

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