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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Inflammation

This article is part of the Research TopicNeutrophil function and dysfunction: Pathways, impact, and therapeutic insightsView all 4 articles

Neutrophil Gene Expression in COVID-19 Patients with Acute Respiratory Distress Syndrome

Provisionally accepted
Hiroshi  ItoHiroshi ItoMasakazu  IshikawaMasakazu IshikawaJumpei  YoshimuraJumpei YoshimuraYuchen  LiuYuchen LiuShuhei  SakakibaraShuhei SakakibaraFuminori  SugiharaFuminori SugiharaHisatake  MatsumotoHisatake Matsumoto*Haruhiko  HirataHaruhiko HirataHiroshi  OguraHiroshi OguraJun  OdaJun OdaDaisuke  OkuzakiDaisuke Okuzaki*
  • Osaka University, Suita, Japan

The final, formatted version of the article will be published soon.

Although an increase in neutrophil count has been observed in patients with coronavirus disease 2019 (COVID-19), the relationship between the systemic neutrophil transcriptome and the clinical course of COVID-19 remains underexplored. Hence, we examined the relationship between the clinical course and RNA sequencing analysis results in COVID-19 patients. Bulk RNA sequencing was performed on peripheral blood samples from 28 COVID-19 patients with acute respiratory distress syndrome (ARDS) and 16 healthy controls. Clustering analysis revealed no differences in the clinical characteristics of COVID-19 patients with ARDS. Subsequently, a separate cohort was created, and only neutrophils were isolated from the peripheral blood of five COVID-19 patients with ARDS for single-cell sequencing. COVID-19 patients with ARDS had elevated gene expression associated with neutrophils compared with healthy controls. Clustering analysis showed that the patients were divided into two groups: those who could be weaned from the ventilator within 28 days and those who could not. The findings indicate that differences in neutrophil gene expression may have clinical implications. This study may support the exploratory identification of genomic factors, such as neutrophil gene expression, that could be relevant to clinical parameters.

Keywords: acute respiratory distress syndrome1, coronavirus disease 2019 (COVID-19)2, neutrophi3, Single-cell RNA sequencing4, gene expression5

Received: 30 Apr 2025; Accepted: 24 Oct 2025.

Copyright: © 2025 Ito, Ishikawa, Yoshimura, Liu, Sakakibara, Sugihara, Matsumoto, Hirata, Ogura, Oda and Okuzaki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Hisatake Matsumoto, h.matsumoto0828@gmail.com
Daisuke Okuzaki, dokuzaki@biken.osaka-u.ac.jp

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