COVID-19: Is G6PDd a major risk factor?

Maria Karanasou
Aug 24, 2020 · 6 min read

Research and awareness needed

source: author’s quick drawing

TL;DR

It seems that more and more people are agreeing that G6PDd can be a risk factor for COVID-19, not only in terms of the medication that is used to combat the virus, but regarding one’s susceptibility to the virus and the severity of its side-effects. There is an urgent need to verify this through numbers and research. The focus of this article is to raise awareness to the matter.

Watch Weighing the Benefits & Risks of the Covid-19 Vaccine for the G6PD Deficiency Pop. 4–8–21

From the first few days of the lock-down, as I watched the news with the number of patients affected and the casualties, I wondered if there could be a relationship between being G6PDd and having serious side-effects from COVID-19, since G6PDd can increase susceptibility to certain infections (while being an advantage in others — especially malaria.).

A few days after, I stumbled upon this:

A petition to raise awareness and research on this matter.

And it got me curious. A quick research brings up a few papers and articles that were entertaining the thought.

“Spain and Italy have been particularly affected by the COVID-19 pandemic, with case fatality rates of 12.0% and 14.2%, respectively, as of the writing. G6PD deficiency is more common in the Mediterranean region. […] In the United Kingdom, 63% of the first 106 health care and social workers who died from the virus were black, Asian, or minority ethnic (BAME). BAME individuals make up 34% of patients admitted to UK intensive care units, although they only account for 17% of the population.

[ … ]

Studies are needed to determine whether a positive correlation exists between G6PD deficiency and COVID-19, with respect to increased susceptibility to infection and severity of illness.” [1]

In general, COVID-19 presents with mild to moderate symptoms to the majority of patients, but there are also patients that have severe acute respiratory syndrome and who progress to a severe form. [1, 3]

Symptoms of COVID-19 include increase in liver transaminases, lower platelets and increase ferritin. And in those who die from the disease, there have been reported venous thromboembolisms. All the above are also evident in people who are dealing with an hemolytic episode due to oxidative stress, or viral or bacterial infection, such as G6PDd people. [2, 3] G6Pd patients are also at an increase probability of developing multiple types of coagulopathy including pulmonary obstructions and rhabdomylolysis [3].

An ex vivo study in 2008 has shown that G6PD-deficient cells are more vulnerable to human coronavirus infection than G6PD-normal cells[4]. The researchers also found that the rate of viral replication was higher in infected cells that lacked G6PD. [2]

Recently, in a Saudi Children’s Hospital, Fluorescent spot test (FST) for glucose-6-phosphate dehydrogenase (G6PD) deficiency was performed in 5 boys and 14 girls that had confirmed COVID-19. Out of those, 4 (80%) boys and 5 (36%) girls were found to be G6PDd. They note that the way their FST was performed indicates that these cases had moderate to severe deficiency. A side note here: FST is not very accurate regarding the identification of heterozygous females [12] , so there is a chance that a more accurate kind of test would show that more girls are deficient. They conclude that they anticipate that G6PDd individuals will be more vulnerable to severe acute respiratory syndrome coronavirus 2, the causative agent of the COVID-19 pandemic, however this needs to be confirmed in a large-scale population-based study [7].

In addition, evidence has shown that severe COVID-19 reactions are due to low endogenous reduced glutathione [11]. Note that a primary reason someone would have low endogenous reduced glutathione would be G6PD deficiency.

It is not just that some of the drugs being administered to COVID-19 patients, namely Chloroquine and Hydroxychloroquine, can cause hemolytic episodes to those with G6PDd. It is also that a) G6PDd people are in general more susceptible to some infections and b) COVID-19 seems to cause extreme oxidative stress [2, 3], which G6PD is needed to overcome.

Currently, a global G6PDD-COVID-19 Taskforce from concerned volunteers has been formulated to highlight their concerns regarding G6PD deficiency. Here’s the open letter they directed to WHO:

Open letter to WHO from the global G6PDD-COVID-19 Taskforce to highlight concerns regarding G6PD deficiency

What I would like to see answered

  • Are G6PDd people more susceptible to the severe reactions of COVID-19?
  • Does having G6PDd mean that if one gets COVID-19, it will be more probable that they will have severe side effects? So, basically, the G6PD status in relation to ICU admissions and deaths.
  • If having G6PDd increases susceptibility to COVID-19, do specific antioxidants, like NAC and A-Lipoic Acid, help to decrease severity and/or improve outcomes?

The difficulties of tracking this down

COVID-19’s fatalities are foremost people over 45[13]. Which means that the probability of them having had a proper G6PDd test beforehand is very low, since even now G6PDd screening is not mandatory everywhere. There is also the case that when going through an hemolytic episode, G6PD values are not accurate since the body is trying frantically to generate new RBCs, and consequently more G6PD is found in the blood stream [8]. So, the way the testing for G6PDd is done also matters.

One possible solution to the above obstacles, as suggested by [8], could be to get numbers from the US military, since they would have the most accurate data, and in addition they are aware of the hemolysis testing issue [6]. The idea is that getting the numbers for those who have G6PDd versus those who don’t in relation to also having COVID-19 would help with a first estimate of the situation and would provide a solid base for research to go on.

If there are any other ideas about this, please let me know.

Just to note that G6PDd was first discovered and studied in the 1950’s after some US soldiers had severe side-effects from anti-malaria drugs (Primaquine) [9] [10]. Note that Chloroquine and Hydroxychloroquine are also such drugs.

In short

If G6PDd is a major risk factor and it plays a role in how serious the manifestation of COVID-19 infection will be, there needs to be more research and awareness about it primarily because of how prevalent this enzyme deficiency is. It also needs to be taken into consideration with any and all treatment options — since many increase oxidative stress. Lastly, if antioxidants can help lower the risk for G6PDd people, then it needs to be clear about which antioxidants and in what dosage.

I hope this helps spread the very much needed awareness. Please, let me know in case I missed something or there’s a mistake anywhere, or just your thoughts on this. It would be nice if more people could also get involved, even by just signing the petition.

Take care and stay safe!

References and Interesting Articles

[1] https://www.mayoclinicproceedings.org/article/S0025-6196(20)30598-X/pdf

[2] https://g6pddf.org/covid-19-g6pd-deficiency-medical-review/

[3] https://www.sciencedirect.com/science/article/pii/S0188440920309486

[4] https://www.researchgate.net/publication/340769033_G6PD_deficiency_in_COVID-19_pandemic_a_ghost_in_the_ghost

[5] https://dd7.c74.myftpupload.com/wp-content/uploads/2020/08/FINAL-Open-Letter-G6PD-Deficiency.pdf

[6] https://health.mil/News/Articles/2019/12/01/Prevalence-of-Glucose

[7] https://www.medrxiv.org/content/10.1101/2020.07.08.20148700v2

[8] https://pdfhost.io/v/ZMgQO9wh5_G6PD_Research_and_Testing_needed_during_pandemic.pdf

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059509/

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199897/

[11] https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00288

[12]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314154/

[13] https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/

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