Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

COVID-19: Beta-Thalassemia Subjects Immunised?

Version 1 : Received: 18 April 2020 / Approved: 19 April 2020 / Online: 19 April 2020 (13:48:56 CEST)

A peer-reviewed article of this Preprint also exists.

Edouard Lansiaux, Philippe Pierre Pébaÿ, Jean-Laurent Picard, Joachim Son-Forget, COVID-19: beta-thalassemia subjects immunised? Medical Hypotheses, 2020, 109827, ISSN 0306-9877, https://doi.org/10.1016/j.mehy.2020.109827. (http://www.sciencedirect.com/science/article/pii/S0306987720308124) Edouard Lansiaux, Philippe Pierre Pébaÿ, Jean-Laurent Picard, Joachim Son-Forget, COVID-19: beta-thalassemia subjects immunised? Medical Hypotheses, 2020, 109827, ISSN 0306-9877, https://doi.org/10.1016/j.mehy.2020.109827. (http://www.sciencedirect.com/science/article/pii/S0306987720308124)

Journal reference: Medical Hypotheses 2020
DOI: 10.1016/j.mehy.2020.109827

Abstract

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent pre-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .

Subject Areas

Novel Coronavirus; respiratory distress; Favipiravir; statistics; correlation; beta thalassemia; immunisation; Italy; Sardinia; regression; heme

Comments (12)

Comment 1
Received: 21 April 2020
Commenter: Randy J Read
The commenter has declared there is no conflict of interests.
Comment: This article is built on extremely weak foundations. The preprint from Liu & Li, cited in the abstract as inspiration for this work, has fatal flaws in its computational methods (https://chemrxiv.org/articles/Flawed_methods_in_COVID-19_Attacks_the_1-Beta_Chain_of_Hemoglobin_and_Captures_the_Porphyrin_to_Inhibit_Human_Heme_Metabolism_/12120912), and it draws scientifically and medically unsound conclusions (https://medium.com/@amdahl/covid-19-debunking-the-hemoglobin-story-ce27773d1096). Unless the conclusions of this article can be supported without any dependence on the speculations by Liu & Li, it should be withdrawn.
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Response 1 to Comment 1
Received: 21 April 2020
Commenter: Edouard Lansiaux
The commenter has declared there is no conflict of interests.
Comment: Thanks for your interest concerning our study which only formulates an hypothesis. This hypothesis has to be confirmed by in vitro and maybe in vivo tests. View of the pandemic context, all possible solutions has to be tested. ----
Response 2 to Comment 1
Received: 21 April 2020
Commenter: Edouard Lansiaux
The commenter has declared there is no conflict of interests.
Comment: Thanks for your interest concerning our study which only formulates an hypothesis. This hypothesis has to be confirmed by in vitro and maybe in vivo tests. View of the pandemic context, all possible solutions have to be tested.
Comment 2
Received: 21 April 2020
Commenter: Randy J Read
The commenter has declared there is no conflict of interests.
Comment: I respectfully disagree with your statement that "all possible solutions have to be tested". When it comes to the hypothesis by Liu & Li that SARS-CoV-2 attacks hemoglobin, there is no valid evidence. There is therefore no justifiable reason for anyone to put in more time on that hypothesis than on any of the vast number of other unsupported speculations that could be put forward. I am not commenting on your work as such; I am just saying that if your work and your conclusions rest on the validity of the preprint from Liu & Li, then they are on extremely shaky foundations. If you can revise your preprint so that it does not require invoking Liu & Li, I will leave it to others to look at the evidence underlying your conclusions. However, if your work cannot be made to stand on its own, then there is no justifiable reason for anyone to carry out the in vitro and in vivo tests to investigate your hypothesis either.
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Response 1 to Comment 2
Received: 22 April 2020
Commenter: Edouard Lansiaux
The commenter has declared there is no conflict of interests.
Comment: One hand, I agree perfectly with you concerning the weak foundations of our study (based only upon the Liu & Li pre-print study which is a study in silico). On the other one, when we formulate the wish to communicate our mathematical results to others that is to do before in vitro or vivo test a epidemiological study on COVID-19 infection severity in the betathalassemic population. Furthermore, our initial hypothesis (the correlation between a possible immunisation against COVID-19 and a minor betathalassemic status) is also based on the similarity between the action mechanism of hydroxychloroquin on malaria ( Coronado, L.M., C.T. Nadovich, and C. Spadafora, Malarial hemozoin: from target to tool. Biochim Biophys Acta, 2014. 1840(6): p. 2032–41.) and COVID-19 (Liu, J., et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov, 2020. 6: p. 16.) and the physiopathology of betathalassemia.
Comment 3
Received: 3 May 2020
Commenter: PIerre Rion
The commenter has declared there is no conflict of interests.
Comment: This is probably a naive question; I have scientific experience but not in any medical specialty. The regression approach above seems sophisticated and with results that are possibly open to multiple interpretations. I would assume that blood work was done at least once for each person in Italy who was deceased by Covid 19. Could a scientific study check the data of deceased patients and flag the low MCV cases and then follow up with these cases to see if any of these were persons had Beta Thal minor? I know that low MCV can be a sign of low Iron but would the number of deceased patients with low MCV not be small enough to just follow up with those subjects and make a definitive conclusion on the suggestion mentioned above (Beta Thal causes immunity to Covid 19)?

I am in Canada with Beta Thallasemia Trait. I have been invited to go back to work. Am I higher risk from COVID-19 or lower risk? When will more conclusive results come from the study above?
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Response 1 to Comment 3
Received: 5 May 2020
Commenter: Edouard Lansiaux
The commenter has declared there is no conflict of interests.
Comment: Thanks for your interest concerning our study. The different hypothesis, that you put in relief, need to be studied, in particular the sensitivity of MCV in the screening and follow up.

Unfortunately, we don't have access to clinical data. So, we are in the obligation to wait thar an other team leads a clinical study on this subject.

Our paper only proposes an hypothesis based upon observationnal study and an in silico physiopathological study. It needs to be confirmed by in vitro and in vivo tests.

Concerning your personal statement, if you are a beta-thalassemic minor trait, according to our study, you are a lower risk from COVID-19.

We are still waiting the peer-review and the clinical and laboratory research is in the hand of the worldwide scientific community.
Comment 4
Received: 1 June 2020
The commenter has declared there is no conflict of interests.
Comment: Hello has there been any further tests into beta-thalassemic minor trait, according to the study, we are at a lower risk from COVID-19 ?
Thank you.
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Comment 5
Received: 12 June 2020
Commenter: Antonio Piga
The commenter has declared there is no conflict of interests.
Comment: I fully agree with Randy J Read's balanced comments and not happy with the authors of this manuscript.
They defend themselves with the convenient statement: "our study only formulates a hypothesis".
At the same time they do express opinions like: "if you are a beta-thalassemic minor trait, according to our study, you are a lower risk from COVID-19".
Very unbalanced, unscientific and not safe.
If the policy of the journal Hypothesis is a full disclosure of the peer review process, I will read it with great interest.
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Response 1 to Comment 5
Received: 15 June 2020
Commenter: Edouard Lansiaux
The commenter has declared there is no conflict of interests.
Comment: For the last but not least time, we have conducted an observational study in order to test, on a mathematical side, an hypothesis formulated by some Italian scientists. This hypothesis has to be considered as valid on a mathematical view but not yet on a physiopathological view. The statement "if you are a beta-thalassemic minor trait, according to our study, you are a lower risk from COVID-19" if it was formulated as it, was effectively unbalanced. "If you are a beta-thalassemic minor trait, you are a lower risk from COVID-19 according to our modest observational study, but it's not an assertation due to the lack of clinical and physiopathological data" would be better.
Comment 6
Received: 15 August 2020
Commenter: Nina
The commenter has declared there is no conflict of interests.
Comment: This is indeed interesting.
My husband recently had covid19 and I did not contract the infection.
I was tested 3 times over 2 week isolation period, all of which were negative to the virus.
I have a beta thalassaemia minor or possible coinheritance pattern. I also have connective tissue disease.
As a young woman with chronic illness I am still really worried about this virus!
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Response 1 to Comment 6
Received: 20 August 2020
Commenter: Nina
The commenter has declared there is no conflict of interests.
Comment: I should also mention I am not on any medications for connective tissue disease/autoimmunity.
I am not taking any plaquenil/DMARDs, Immunosuppressants, Steroids...
I'm currently not taking any drugs to manage so there is no additional factor that could influence this outcome.

I am sick most of the time. And i think my immune system really got hyped up for a week there while my husband was most unwell/active with covid19. I definitely was having a flare of some kind in response to him shedding the virus. But I didn't catch coronavirus... much to my surprise and our relief.

Also interested in androgen and this virus. But that is another topic for another time!

I definitely would love to know if beta thalassaemia is protective in some way. It is such a problematic thing to have, as I am always anaemic and trying to replace the iron has lead to problems with my pancreas and heart arrhythmias in the past.

Good luck with your investigation.

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