A Tale of Two Letters About Remdesivir - Enter Mind – Exit Remdesivir?

A Tale of Two Letters About Remdesivir – Enter Mind – Exit Remdesivir?

October 16, 2020 Minding Corona No Comments

Remdesivir or ‘We,’ Which Cure Will it Be?

Intrigued by the antiviral drug, remdesivir, I delved into scientific studies about it. The result is a duo of ‘Letters to the Editor’ to the new England Journal of Medicine (top journal of medical science), in May and June 2020. Not even hoping they would accept, indeed, they didn’t. The stakes are too high. The direction too non-mainstream. This way, I can publish it anywhere else. This is also part of my book MINDING CORONA.

NOTE: In a preprint on medRxiv, 15 October 2020, of an article by the WHO Solidarity Trial Con-sortium, remdesivir “appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay. The mortality findings contain most of the randomized evidence on Remdesivir” [https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1] My intention, five months ago, was not to debunk remdesivir, but to show the open – yet seemingly invisible – place for the influence of the mind in this research, thus in COVID progression and management. In order not to see this, one needs to actively look in the other direction. That’s worse than blindness. Isn’t our mind our most precious asset? When are we going to respect it?

Here are the two letters:

Remdesivir or ‘We,’ Which Cure Will it Be?

(submitted May 18, 2020)

Generally, the human mind has no place in causal thinking about COVID-19 progression in the lay press, nor in science. This may be a huge mistake. The exclusive focus lies on material cause and therapies. Even in the latter, the mind may be invisibly intermingled. Making it visible leads to better treatment.

For instance, the Grein study¹, concerning the effect of the broad-spectrum antiviral drug remdesivir on COVID-19, lacks placebo-based randomization. More rigorous studies are being conducted of which fewer than a quarter are double-blind. The most powered and well-conducted research is the ongoing NIAID study, using an inactive placebo (no active ingredients). Preliminary results focus on benefits (mainly, time of recovery) outweighing harms of remdesivir without further concern for the placebo group. In view of the dire need, a second question is more critical than ever: Can the placebo group show us the influence of mind in COVID-19 progression?

Psychoneuroimmunology shows mind-body influences in many health-related domains.² There is clear and bidirectional influence of mind on viral diseases.³ In 2012, we argued a general scheme for understanding mind-related influences of true placebo apart from study biases.⁴ The second question is as crucial as anything.

How double-blind is a study? Asking patients bluntly to which group they belong, they don’t know. Asking them to guess, adverse effects may make them guess correctly. Double-blindness strives also to eliminate unconscious influences from testing result. Therefore, we need to look also at unconscious blindness, especially in suggestible circumstances and immense stress. One needs not to look further. In the [Grein et al., 2020] study, adverse effects (increased hepatic enzymes, diarrhea, rashes, renal impairment, hypotension) were reported in 60% of patients. This makes double-blindness doubtful, heightening blindness to the relative effect of mind in both study groups. We deserve better especially now.

A vaccine may still take a long time to be developed. No therapies for COVID-19 have been adequate to date. Remdesivir may have some effect, but little and at a considerable cost (adverse reactions). A true placebo effect would show that mind-related factors play a significant role, as is theoretically probable. Knowing about mind-COVID influence may inspire health-promoting communications. Tools can be made available at a grand scale for individual help. A.I. can be integrated towards enhancing these tools and towards input of real-world scientific data. Lives can be saved. Making social contacts safer this way may significantly impact the economy and flatten disasters also in countries like India and Brazil.

References

1. Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe COVID-19 [published online ahead of print, 2020 Apr 10]. N Engl J Med. 2020;NEJMoa2007016.

2. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601–63.

3. Coughlin SS. Anxiety and Depression: Linkages with Viral Diseases. Public Health Rev. 2012;34(2):92.

4. Mommaerts JL, Devroey D. The placebo effect: how the subconscious fits in. Perspect Biol Med. 2012;55(1):43‐58.

Enter Mind – Exit Remdesivir?

(submitted June 4, 2020)

Letter to the editor in reference to: Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of COVID-19 – Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;10.1056/NEJMoa2007764. doi:10.1056/NEJMoa2007764

The prematurely finished remdesivir-trial published by Beigel et al.¹ may prove that mind, not remdesivir, influences COVID-19 progression.

Infusion reactions have been noted shortly after administration², influencing patients’ treatment assumptions, enhanced through daily kindling, breaking double-blind. With patients knowing when they received some product¹, we refer to hidden-administration trials where effects are grossly dependent on such patient knowledge³. Remdesivir heightens transaminases up to 20-fold², patients with already high transaminases being excluded². This suggests the correct group allocation to caregivers, breaking double-blind. Moreover, all placebos were passive².

The baseline-5 group is arguably most suggestible. Here lies the positive effect of remdesivir-administration in contrast to other groups, most intriguingly baseline-7. Apparently, for remdesivir-administration to work, patients are necessarily fully conscious. This, together with a counter-intuitive effect from day one, may show the effectiveness not of remdesivir, but of the mind.

We hypothesize that the absence of mind in COVID-19 causal thinking cost many more lives than remdesivir could ever save. We urge appropriate research. It would be devastating to see the need for this only in retrospect.

References

(1) Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of COVID-19 – Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;10.1056/NEJMoa2007764. doi:10.1056/NEJMoa2007764

(2) Fact Sheet for Healthcare Providers – Emergency Use Authorization (EUA) of Remdesivir (GS-5734TM) [Internet]. U.S. Food and Drug Administration (FDA). 2020. Available from: www.fda.gov/media/137566/download

(3) Benedetti F, Carlino E, Pollo A. Hidden administration of drugs. Clin Pharmacol Ther. 2011;90(5):651‐661. doi:10.1038/clpt.2011.206