Authors Retract, Resubmit 'Very Poorly Conducted' Meta-Analysis of COVID-19 Treatment

Retraction Watch Staff

December 02, 2021

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A journal has retracted a meta-analysis on Covid-19 after concerned readers complained about the quality — or lack thereof — of the study.

The article, "A meta-analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody treatment for COVID-19 patients," appeared in Therapeutic Advances in Chronic Disease, a SAGE title.

According to the retraction notice:


At the request of the Journal Editor, SAGE Publishing and the authors, the following article has been retracted.
Guan J-T, Wang W-J, Jin D, et al. A meta-analysis of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody treatment for COVID-19 patients, first published online 20 August 2021. DOI: 10.1177/20406223211039699 .
The authors of the journal were notified of errors in their meta-analysis, after publication, through a letter to the Editor https://journals.sagepub.com/doi/full/10.1177/20406223211050495 and an independent email from Dr Stefan Steidl, Vice President, Disease Biology & Translational Research, on 27 August 2021. When re-examined, the authors noted that they had mistakenly included several studies evaluating the role of IL-6 inhibitors and concluded that they needed to do an updated search and analysis https://journals.sagepub.com/doi/full/10.1177/20406223211055922 . For this reason, the article has been retracted and will be republished, if appropriate, following additional peer review of the new data.

It is the 198th retraction of a paper about COVID-19, according to our count.

Steidl has published on GM-CSF and is a vice president at MorphoSys, a biotech in Germany that focuses on antibodies.

At the heart of the published letter is the following paragraph:

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 to inhibition of specific "downstream" cytokines such as IL-6, IL-1 or TNF. While GM-CSF inhibition can lead to decrease in reduced levels of these downstream cytokines by inhibiting the myeloid precursor cell maturation, GM-CSF also plays an important role in alveolar macrophage maturation and improving antigenic clearance by promoting lung sentinel cell-mediated immunity. 2 Further, as with other immunosuppressive agents, risk of secondary infections exists with GM-CSF inhibitors. Until better further clinical trials can prove their efficacy, the use of GM-CSF inhibitors in COVID-19 shall be limited to clinical trials under strict medical supervision.

Pankaj Bansal, of Mayo Clinic in Jacksonville, Fla., a coauthor of the letter, added in an email us that he felt the meta-analysis was "very poorly conducted":

The authors claimed efficacy of a drug based on the metaanalysis of 12 studies, out of which, only 2 were evaluating the drug of interest, clearly misrepresenting the available data on the drug of interest. In the times of COVID-19, researchers have a moral obligation to present and publish high quality data, to prevent any misrepresentation of therapeutic options for this disease. What was even more surprising is that the metaanalysis was published in a well-respected peer reviewed journal, and how this article "escaped" the review process by the reviewers and editors is very surprising. This significant shortcoming of the article shall have been detected by the editor before/after the peer-review, and by the reviewers during the peer-review, and publication of this article raises serious questions about the peer-review process as well.

A SAGE spokesperson told us:

This paper was reviewed by two external reviewers and underwent two rounds of robust peer review in line with SAGE's standard procedures. After being alerted to possible issues with the meta-analysis by members of the scientific community, SAGE launched an immediate investigation into the article and published a letter to the editor that outlines the issues, as well as a response from the article's authors. The investigation concluded with the retraction of the article in November 2021. SAGE takes issues of scientific accuracy extremely seriously and makes every effort to act quickly and transparently to correct the academic record when errors are identified.

Robust, it seems, is a relative term.

In their response, the authors describe their re-analysis:

In our update meta-analysis, a total of six eligible literature involving 1542 COVID-19 patients were recruited, including anti-GM-CSF therapy treatment group (n = 761) and control group (n = 781). Using a random-effect model, we found that the GM-CSF antibody treatment was associated with a 4.3–26.9% decline of the risk of death [odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.53–0.95, p = 0.02], a 5.3–28.7% reduction of the incidence of invasive mechanical ventilation [OR = 0.53, 95% CI: 0.31, 0.90, p = 0.02], and a 23.3–50.0% enhancement of ventilation improvement [OR = 11.70, 95% CI: 1.99, 68.68, p = 0.006]. Besides, GM-CSF antibody treatment did not have a significant correlation to secondary infection. Thus, the main results of our new analysis still support our previous conclusion that severe COVID-19 patients can benefit from GM-CSF antibodies, though further randomized controlled trials are still needed for further verification.

But that didn't save the paper.

Zheng-Hao Xu, of the Institute of TCM Clinical Basic Medicine at Zhejiang Chinese Medical University, in Hangzhou, and the senior author of the paper, told us:

We agree with this decision, and we have already resubmited the paper. Thanks for your attention.

Xu added:

We have resubmitted it to the same journal (Therapeutic Advances in Chronic Disease) after we corrected and updated it. The resubmitted paper is now named as "Granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies treatment for COVID-19 patients: a corrected and updated meta-analysis."


 

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