Low dose of hydroxychloroquine – but lots of questions

Last week, a new retrospective study from Tongji Hospital in Wuhan was published in Science China Life Sciences (a Springer Link journal). The study found 47% fatalities in critically ill #COVID19 patients that were given regular treatment, and only 19% fatalities in patients treated with low doses of hydroxychloroquine (HCQ).

These results sound amazing.

But I took a closer look. And I have lots of questions.

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COVID-19, small RNAs, and conflicts of interest

Recently a paper published in Nucleic Acid Therapeutics, a Mary Liebert publication not to be confused with the more glamorous Nucleic Acid Research journal, was brought to my attention. It described the potential use of small RNAs as a therapeutic against SARS-CoV-2.

Alas, it is most memorable because of the alarmingly short time-to-acceptance, lack of references, and the omission of several conflicts of interest.

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Thoughts on the Prevent Senior study

A new study from Brazil is reporting significant positive effects of hydroxychloroquine (HCQ) + azithromycin (AZM) on early-stage suspected COVID19 cases. The study was posted as a preliminary manuscript draft on Dropbox a couple of days ago. I just tweeted my thoughts in a long thread, but here is a bit more polished version.

Update 20 April: It was announced today that the study described below has been suspended because of ethical violations. As pointed out by Natalia Pasternak and Carlos Orsi and Ricardo Parolin Schnekenberg (see Additional Reading links below), the study had already started before the ethical approval had been obtained. This could be figured out by looking at the disclosed study days in the preprint and the trial registration at the Clinical Trials website.

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Amazing rates

The IHU Mediterranee Infection, the Marseille hospital that claims that hydroxychloroquine + azithromycin treatment will cure almost everyone infected with COVID-19 has been reporting very low death rates for COVID-19 patients. As of today, their website reports that the IHU has a much lower death – 1.7% – than the worldwide COVID-19 mortality rate of 6.2%.

While that might look amazing at first glance, these numbers are not surprising, given the high numbers of virus tests that the institute has been performing. Let’s take a closer look at their testing to better understand how the Marseille hospital can get such low mortality rate numbers.

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ISAC shares concerns about the Hydroxychloroquine and Azithromycin paper

The International Society of Antimicrobial Chemotherapy (ISAC) has shared concerns about the Gautret et al. paper published in its own journal. This paper, published under senior authorship of Didier Raoult from the IHU-Méditerranée Infection in Marseille, describes a small study that showed remarkable effects of Hydroxychloroquine and Azithromycin treatment in COVID-19 patients.

After world leaders and politicians started to tweet and endorse this study, many people pressured health officials to start treating COVID-19 patients with this regime, although the study was small and not yet confirmed by independent, larger, and better randomized other studies.

Several scientists and medical professionals, including myself, had concerns about how patients were assigned to each treatment group, how PCR results were reported, why patients with a poor outcome had been left out of the final results, and how this treatment could potentially result in serious side effects. I wrote about my concerns in this blogpost and on PubPeer.

Now, ISAC, who is overseeing the International Journal of Antimicrobial Agents, the journal that published this study, has joined in those concerns.

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An observational study without a control group

This blog post is based on a Twitter thread I did on March 27, 2020, after seeing Mathieu Rebeaud’s Tweet about a new white paper from the institute of Didier Raoult. That not-yet peer reviewed paper describes a group of 80 COVID-19 patients, all treated with a combination of hydroxychloroquine and azithromycin. This treatment had shown some promising results in a very small, not well-executed study by the same group. Unfortunately, this second study does not have a control group and the patients did not appear to be very sick. So here is my critical review.

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Post-publication reviews on COVID-19 papers

We are in the midst of a viral pandemic with huge effects on human health, social interactions, and the economy. Suddenly, lots of people have opinions or claim to have solutions to solve the COVID-19 situation. Not surprisingly, the Coronavirus epidemic has led to an enormous input of scientific papers, editorials, letters, reviews, trials, and what have you not. Most of these have been written hastily, without the rigor and thoughtfulness and editing that are normally essential to scientific publishing. Some of these papers are great, many of them not so much. Social media is exploding with all kinds of post-publication reviews of heavily discussed scientific papers. This post is an attempt to collect critical reviews of some of these COVID-19 related scientific papers.

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