Neutrophils in COVID-19: recent insights and advances

Abstract

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can lead to acute respiratory distress syndrome (ARDS), multi-organ failure and death, posing significant threat to human health. Studies have found that pathological mechanisms, such as cytokine storms caused by uncontrolled innate immune system activation, release of damage-associated molecular patterns during tissue injury and a high incidence of thrombotic events, are associated with the function and dysfunction of neutrophils. Specifically, the increased formation of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs) has been shown to be closely linked with the severity and poor prognosis in patients with COVID-19. Our work focuses on understanding the increased number, abnormal activation, lung tissue infiltration, and elevated neutrophil-to-lymphocyte ratio in the pathogenesis of COVID-19. We also explore the involvement of NETs and LDNs in disease progression and thrombosis formation, along with potential therapeutic strategies targeting neutrophil and NETs formation.

A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection

“…In the multifaceted pathogenesis of COVID-19 and sepsis-induced ARDS, the uncontrolled activation and subsequent degranulation of neutrophils are central ( 44 , 45 ). These key cells in the innate immune response can, when dysregulated, release excessive granules containing proteolytic enzymes and reactive oxygen species, leading to substantial cytotoxicity ( 45 , 46 ).…”

“…This process damages the lung’s alveolar epithelial cells and disrupts the extracellular matrix, contributing to endothelial barrier dysfunction ( 46 ). Simultaneously, the release of inflammatory mediators like cytokines and chemokines can amplify the inflammatory response into a “cytokine storm,” potentially causing systemic inflammation that affects multiple organs ( 28 , 44 , 45 , 47 ). Hence, our findings offer new insights into the molecular mechanisms underlying COVID-19 and sepsis-induced ARDS and suggest CD3, CD247, CD2, CD40LG MMP-9, LCN2, and RETN as the potential targets for neutrophils in developing novel therapies and diagnostic tools for these diseases.…”

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

“…Furthermore, MET modulates the function of neutrophils by decreasing the formation of neutrophil extracellular traps (NETs) [ 100 ]. This effect is particularly relevant considering the involvement of neutrophils in various complications of SARS-CoV-2 infection [ 101 ].…”

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

“…В развитии органной патологии, связанной с тромбовоспалением при COVID-19 и при ИВРЗ, обсуждается роль нейтрофилов [192,193]. Среди механизмов, определяющих как «физиологическую», так и «патологическую» функцию нейтрофилов, особое внимание привлечено к способности нейтрофилов формировать «сетевые» (web-like) структуры, получившие название «нейтрофильные внеклеточные ловушки» или NETs (neutrophil extracellular traps) [194,195].…”