The publisher Frontiers has published an expression of concern for an article that proposed “ivermectin protects against COVID-19” via effects on the microbiome.
The article, “Microbiome-Based Hypothesis on Ivermectin’s Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity,” was published in July 2022 in Frontiers in Microbiology. The sole author, Sabine Hazan, is affiliated with ProgenaBiome, a company based in Ventura, Calif. that “spearheads the movement of validating, verifying, and clinically applying its sequencing data, to better understand the microbiome.”
The abstract of the article stated:
Ivermectin is an anti-parasitic agent that has gained attention as a potential COVID-19 therapeutic. It is a compound of the type Avermectin, which is a fermented by-product of Streptomyces avermitilis. Bifidobacterium is a member of the same phylum as Streptomyces spp., suggesting it may have a symbiotic relation with Streptomyces. Decreased Bifidobacterium levels are observed in COVID-19 susceptibility states, including old age, autoimmune disorder, and obesity. We hypothesize that Ivermectin, as a by-product of Streptomyces fermentation, is capable of feeding Bifidobacterium, thereby possibly preventing against COVID-19 susceptibilities. Moreover, Bifidobacterium may be capable of boosting natural immunity, offering more direct COVID-19 protection. These data concord with our study, as well as others, that show Ivermectin protects against COVID-19.
The article’s conclusion, however, focused on ivermectin as a therapy for COVID rather than a prophylactic:
We are hypothesizing the IVM mechanism of action as a therapeutic for COVID-19 is through feeding of Bifidobacterium, which then inhibits cytokine function and tames the cytokine storm (Figure 1). As such, IVM should be administered at the time of the cytokine storm.
According to Frontiers, the paper has received more than 50,000 views, more than the number of views for 99% of the publisher’s other articles. Altmetric shows thousands of tweets about the article, giving it an attention score in the top 5% of all the research the company monitors. The article has not been cited in other scientific papers, according to Clarivate’s Web of Science.
Starting in December 2022, commenters on PubPeer posted questions about the paper, such as why it referred to data that it did not appear to provide, and missing or inappropriate citations.
After the fifth posted comment, about the format of a company name in the conflict of interest statement, Hazan replied: “Yes I can correct that. Thank you.”
Additional commenters posted more questions, including Elisabeth Bik, who worked in microbiome research at Stanford and a private company before her current fame as a scientific sleuth, but Hazan did not reply again.
On January 5, Frontiers published the following expression of concern for the paper:
With this notice, Frontiers states its awareness of the serious concerns raised regarding this article, which are now under investigation. The situation will be updated as soon as the investigation is complete.
As is typical for Frontiers, but not considered best practice, the original article page does not link to the expression of concern or otherwise indicate it exists. The editorial office for the company did not respond to our request for comment.
Hazan did not reply to Retraction Watch’s request for comment, but an account on Twitter that interacts with her frequently and called her a “beautiful, intelligent, innovative woman-of-color scientist,” tagged us in a tweet after we sent our email. Hazan also tweeted the following about scrutiny of her work:
In February 2022, the US Food and Drug Administration sent Hazan a warning letter in her capacity as president of Topelia Therapeutics, informing her of “objectionable conditions” its inspectors observed in a visit to her company’s clinical research site. Specifically, the company had continued to enroll, randomize, and administer investigational drugs to research participants after the ethical approval for its protocol from an institutional review board had lapsed.
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“an account on Twitter that interacts with her frequently”
That sounds so much nicer than “sockpuppet”.
Anyone can criticize a theory article. While I question the utility of publishing medical theories, Hazan is correct in saying “prove me wrong”.
You may wish to read the paper and comments on PubPeer.
Hazan is demonstrably wrong in claiming that cited sources support her theories, when in fact they disprove them or are irrelevant. She really should read sources before citing them.
Personally, I think she relies upon “medical writers” to ghost write some of her papers. Occasionally, they show up as go-authors or in the Acknowledgements. Maybe she can get a refund on this one.
* co-authors
In addition to the FDA warning letter, in the past she’s also faced some disciplinary measures on her medical licenses:
https://apps.health.ny.gov/pubdoh/professionals/doctors/conduct/factions/FileDownloadAction.action?finalActionId=6029&fileName=lc215073.pdf&fileSeqNum=1
https://apps.health.ny.gov/pubdoh/professionals/doctors/conduct/factions/FileDownloadAction.action?finalActionId=6029&fileName=lc215073.pdf&fileSeqNum=1 (Page 12)
(If the links work)
The problem with ivermectin as a COVID-19 therapeutic is that its patent has expired.
Or, y’know, the problem could be that it doesn’t provide any therapeutic effect at all against COVID-19.
The literature on the therapeutic effect is abundant, so the evidence is rather solid. Check the literature!
I just checked the literature, and it shows it doesn’t work.
Now explain why dexamethasone is recommended in treatment guidelines, despite the patent being long-expired. I’ll wait.
The author has expressed some unconventional views on Twitter about research publication norms.
https://twitter.com/sabinehazanmd/status/1620121554498781185
“It’s a Hypothesis again … I can put whatever article I want to… it’s MY NARRATIVE… MY HYPOTHESIS… NOT A SYSTEMATIC REVIEW… #ROAR IS PUBMED compromised? Is Frontier compromised? Is Peer Review compromised? Let’s see the truth because from where I stand, this is MY HYPOTHESIS.”
“It’s MY HYPOTHESIS and I’ll cry if I want to…”
Per Dr. Hazan on Twitter, the paper is being retracted.
https://twitter.com/Thatsregrettab1/status/1648451636652830721?s=20
Retracted May 3, 2023. See https://www.frontiersin.org/articles/10.3389/fmicb.2023.1216170/full for the “not so detailed” retraction notice, relevant portion below:
“Following publication, concerns were raised regarding the scientific validity of the article. An investigation was conducted in accordance with Frontiers’ policies. It was found that the complaints were valid and that the article does not meet the standards of editorial and scientific soundness for Frontiers in Microbiology; therefore, the article has been retracted. ”
Left unaddressed: how did the paper get published in the first place? One hint, identified by Dr. Elisabeth Bik, is that one of the peer reviewers was cited 6 times in this paper. That suggests that perhaps the peer review was compromised. While this was brought to the attention of the journal (via email and the PubPeer posts), the journal made no mention of this in the retraction statement. See https://pubpeer.com/publications/1F4FD2BEEBCD740ECF4C6D1C8805BF#10 for Dr. Bik’s concerns.
Finally, credit to Dr. Richard M. Fleming for bringing this paper to my attention in the first place. When he commented on it on Twitter in December and added it to his website, I became immediately suspicious (https://twitter.com/doctor_i_am_the/status/1601276991021678592?s=46&t=6ZEuSkSQwwiOppwGDv3Pvw)
On X, the author has shared correspondence with the publisher. Saved here: https://pubpeer.com/publications/1F4FD2BEEBCD740ECF4C6D1C8805BF#32