The mysterious case of the retracted studies

Hi there!

This week I have a roundup of the new(ish) things in COVIDland, including a flashback to the eighties and how collaboration can take a project to the next level.

Enjoy 😊

PAC-MAN AGAINST COVID-19

Has the yellow video game character retuned from the eighties? No, this is another PAC-MAN: a research team in Stanford was working on a project using the gene-editing technology CRISPR against influenza when SARS-CoV-2 emerged. They quickly changed the subject of their research and teamed up with investigators from the Department of Energy’s Lawrence Berkeley National Laboratory to develop a technique called prophylactic antiviral CRISPR in human cells, or PAC-MAN. This technique messes up viral genome, thus inactivating it. You can read more about the technology in this Cell paper, which also has a compelling graphical abstract. Go PAC-MAN!

The collaboration with Berkeley scientists was important to develop an effective delivery method. Having done my master’s thesis in particle design for respiratory delivery systems, I am very aware that this is an important issue. What’s very cool in this story is that the Stanford team working on CRISPR had no experience in delivery systems, so what did they do? They tweeted for help! Besides that, they published a pre-print, in hopes of attracting someone who worked in that area. By chance or by tweet, they attracted the attention they were looking for and started collaborating with Michael Connolly at Berkeley Lab’s Molecular Foundry. I’ll keep an eye on their efforts.

NOW YOU HAVE A STUDY, NOW YOU DON’T

I was going to talk about the Lancet study in which researchers were unable to find a benefit associated with the use of chloroquine or hydroxychloroquine in COVID-19, but I was late to the party. This study was published in May 22^nd—which is like, ancient times in COVID era—and in the meantime the authors retracted their publication, alongside with another publication in the New England Medical Journal. The reason behind the retractions was an issue with the data used for both studies. Surgisphere, the company responsible for the data sets they used, was unable to provide the necessary raw data for validation by independent auditors, thus leading to inability to replicate results. The company claims that their “data use agreements with (…) institutions prevents us from sharing patient level data or customer names.” Mandeep Mehra, the lead author on both studies, is cited in this Nature news article saying: “Since we do not have the ability to verify the primary data or primary data source, I no longer have confidence in the origination and veracity of the data, nor the findings they have led to.” Indeed.

(Note: I removed the link to the Surgisphere website since it appears to be down)

A FRIENDLY REMINDER

The European Medicines Agency (EMA) issued a reminder about the known adverse effects of chloroquine and hydroxychloroquine, namely cardiac arrhythmias and cardiac arrest. Knowing how much these two medicines are being prescribed off-label, I think this reminder is unfortunately necessary, especially if the patient receiving them already has heart problems or if they are used with other medications that increase the QT interval, such as azithromycin.

MOVING ON TO THINGS THAT WORK…

…or at least are showing positive results. A preliminary report from the Adaptive COVID-19 Treatment Trial (ACTT) is now available at the New England Medical Journal, showing that remdesivir “was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection.” The ClinicalTrials.gov archive shows changes in outcome measures, which are problematic in some cases, but in this instance I think the updated text is clearer. These are promising results, let’s wait for the rest of the results.

On the medical devices front, Roche Elecsys IL-6 test was granted emergency use authorisation (EUA) by the FDA. This test measures interleukin-6 levels in patients, which is a cytokine that signals the development of a possible cytokine storm, a dangerous inflammatory immune response. One of the main challenges of COVID-19 is to know who is at risk of developing more severe disease, and the Roche diagnostic test may help to make the distinction at an early point in the disease course. Roche also has its IL-6 inhibitor Actemra/RoActemra (tocilizumab) in phase 3 trials as a potential therapy for SARS-CoV-2, both alone and in conjunction with remdesivir.

That will be all from me this week, I hope you found it useful.

Let me know what you think in the comment box below 🙂