2020
DOI: 10.1016/s2213-2600(20)30267-8
|View full text |Cite
|
Sign up to set email alerts
|

Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities

Abstract: The COVID-19 pandemic is a global public health crisis, with considerable mortality and morbidity exerting pressure on health-care resources, including critical care. An excessive host inflammatory response in a subgroup of patients with severe COVID-19 might contribute to the development of acute respiratory distress syndrome (ARDS) and multiorgan failure. Timely therapeutic intervention with immunomodulation in patients with hyperinflammation could prevent disease progression to ARDS and obviate the need for… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

2
116
1
3

Year Published

2020
2020
2022
2022

Publication Types

Select...
8
1

Relationship

0
9

Authors

Journals

citations
Cited by 126 publications
(122 citation statements)
references
References 58 publications
2
116
1
3
Order By: Relevance
“…In fact, several studies found a clear relationship between the hyper-inflammatory state and the severity of the disease [6] , [7] , [8] , [9] . The pharmacological approach for treating ARDS needs of novel anti-inflammatory reagents as different COVID-19 patients might respond differently to these treatments [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] .…”
Section: Introductionmentioning
confidence: 99%
“…In fact, several studies found a clear relationship between the hyper-inflammatory state and the severity of the disease [6] , [7] , [8] , [9] . The pharmacological approach for treating ARDS needs of novel anti-inflammatory reagents as different COVID-19 patients might respond differently to these treatments [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] .…”
Section: Introductionmentioning
confidence: 99%
“…NCT04341116, NCT04351243, NCT04351152, NCT04376684) 31,35,36 . In a recent clinical study, repetitive intravenous infusion of an anti-human GM-CSF mAb (Lenzilumab, 600 mg, thrice) significantly improved blood oxygenation, and simultaneously reduced blood levels of two pro-inflammatory cytokines (e.g., IL-1α and IL-6) in 11 out of 12 patients with severe COVID-19 37 .…”
Section: Discussionmentioning
confidence: 99%
“…GM-CSF also appears central in driving inflammation locally and systemically, 5 and experimental models of acute lung injury support this hypothesis, demonstrating that resident alveolar macrophages secrete a variety of inflammatory cytokines that lead to the influx of innate cells including neutrophils, fur-ther amplifying the activation of alveolar epithelial cells and tissue damage. 8 The capacity of GM-CSF to amplify inflammatory response within the lung and its systemic effects, mediated by linking the release of upstream inflammatory cytokines such as IL-1, IL-6, and TNF across monocytes and macrophages and activated T cells in a positive feedback loop, highlight its potential importance in driving systemic inflammation and disease. However, as noted above, adding to the complexity is that GM-CSF is also a critical cytokine for healthy pulmonary function and is necessary for the maturation and maintenance of alveolar macrophages; and in some experimental models, it confers resistance to viral respiratory balance, underscoring that all putative inflammatory cytokines also play roles in integrated host defense.…”
Section: ■ Basic Immunology Of Gm-csfmentioning
confidence: 99%
“…Giving an immunomodulator too early in the course of the infection will compromise an evolving adaptive immune response and may theoretically prolong the disease and compromise the outcome. 2,8 At the moment there is no definitive single biomarker or set of biomarkers capable of identifying the optimal timing of such interventions. How this therapy will fare used singly or in combination with antiviral therapy or glucocorticoids, which are at the moment in ascendency for treatment of COVID-19, will require larger and more carefully conducted trials.…”
Section: ■ Safety Concernsmentioning
confidence: 99%