key: cord-1020727-apn3uxdf
authors: Bansal, Pankaj; Sanghavi, Devang
title: Correspondence to: “A meta-analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody treatment for COVID-19 patients.”
date: 2021-10-28
journal: Ther Adv Chronic Dis
DOI: 10.1177/20406223211050495
sha: 3b99c10f56358878b6ea3ba823d089edefee2e47
doc_id: 1020727
cord_uid: apn3uxdf

nan

To the Editor, We read with great interest the metaanalysis by Guan et al. 1 evaluating the role of granulocytemacrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19. The authors included 12 studies for review, and the metaanalysis suggests potential benefit of anti-GM-CSF therapy in COVID-19 including lower risk of mortality and enhancement of ventilation.

GM-CSF is involved in steady state myelopoiesis, and induces production of granulocytes, monocytes, dendritic cells, and macrophages from progenitor cells. In COVID-19, pathological overactivation of myeloid cells cause by dysregulated GM-CSF expression has been proposed to be contributory in causing cytokine storm and tissue death via release of proinflammatory cytokines including interleukin-1 (IL-1), IL-6 and tumor necrosis factor (TNF). 2, 3 Elevated levels of GM-CSF as well as these proinflammatory cytokines have been observed in patients with COVID-19, thus raising interest in potential role of their blockage as potential treatment of COVID-19. 4, 5 The metaanalysis by Guan et al. is titled "A metaanalysis of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody treatment for COVID-19 patients" and implies this metaanalysis evaluates anti-GM-CSF therapy. However, as mentioned in the study methods and search strategy, the authors did not limit the search to anti-GM-CSF therapy. Studies evaluating role of IL-6 inhibitors including (tocilizumab, siltuximab, sarilumab) in COVID-19 were also included in search methods for this metaanalysis. Although the inclusion criteria for this metaanalysis suggests inclusion of studies evaluating anti-GM-CSF therapy, of the 12 studies included in this metaanalysis, only 2 studies evaluated anti-GM-CSF therapy (Temesgen et al. and De Luca et al.) , while all the remaining studies evaluated IL-6 inhibitors compared to control groups. 6, 7 The 2 studies in this metaanalysis that evaluated anti-GM-CSF therapy are both small single center cohort studies. De Luca et al. 7 prospectively evaluated the role of mavrilimumab, an anti-GM-CSF receptor-α monoclonal antibody in inpatients with severe COVID-19. Use of mavrilimumab was associated with clinical improvement, days to clinical improvement, days to discharge, days to fever resolution and C-reactive protein reduction. However, the study did not reach statistical significance in improvement in mechanical ventilation or death. Temesgen et al. 6 retrospectively evaluated the role of lenzilumab, a recombinant monoclonal antibody targeting human GM-CSF in hospitalized patients with severe COVID-19. Use of lenzilumab was associated with days to clinical improvement and days to discharge. However, no statistically significant improvement was noted in mortality, need for mechanical ventilation, incidence of clinical improvement or days to fever resolution. Given the small sample sizes, heterogenicity of results and both studies not showing improvement in mortality or need for mechanical ventilation, no conclusion can be drawn about the efficacy of anti-GM-CSF therapy in COVID-19 based on these studies.

Although this metaanalysis aims to evaluate role of GM-CSF inhibition in COVID-19, most of the studies in this metaanalysis do not evaluate GM-CSF inhibition and rather evaluate IL-6 inhibition. GM-CSF inhibition is not equivalent

A metaanalysis of granulocyte-macrophage colonystimulating factor (GM-CSF) antibody treatment for COVID-19 patients

GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches

Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients

Author correction: pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

GM-CSF neutralization with lenzilumab in severe COVID-19 pneumonia: a case-cohort study

GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pankaj Bansal https://orcid.org/0000-0001-6315-6879