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Chloroquine and hydroxychloroquine in covid-19

BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1432 (Published 08 April 2020) Cite this as: BMJ 2020;369:m1432

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Re: Chloroquine and hydroxychloroquine in covid-19. Chloroquine may kill many people in Africa, Italy, New York and elsewhere

Chloroquine may kill many people in Africa, Italy, New York and elsewhere

Dear Editor

Reading the article" Chloroquine and hydroxychloroquine in covid-19" and scanning the responses I got a little bit nervous because I missed something. I worked in a clinic for tropical medicine (Bernhard-Nocht-Institute, Hamburg) and later visited several countries in Africa to see a lot of health care facilities working hard with little resources. Malaria and anti-malaria drugs were always a main topic.

When I noticed that WHO and many others advocate the use of hydroxychloroquine (HCQ), if the SARS-CoV-2 test is positive, I was astonished to meet the drug in this context again.

HCQ is an old malaria drug, used also with autoimmune diseases but is not yet officially approved for Covid-19. The recently registered studies with HCQ (I found more than 100 on 18/4/2020, 35 new ones last week (1)) also want to use HCQ alone or in combination with other drugs. HCQ has already been "compassionately" used in some countries even without the framework of a clinical study.

It was used even in completely healthy people "for the prevention of severe courses". It is also used prophylactically for medical staff. The recommended dose is about 20 times as high as for malaria prophylaxis! (400-800mg per day). Such use and even new production facilities (e.g. in Cameroon (2)) for HCQ are currently being ramped up, especially in Africa.

All this happens without sufficient evidence for a positive clinical effect of HCQ in SARS-CoV-2 positives, not to speak about test negatives.

However, HCQ was a long time ago identified to be one of the drugs (3) that cause severe damage to erythrocytes in cases of hereditary glucose-6-phosphate dehydrogenase (G6PD) deficiency.

As an effect of HCQ in those patients we see haemolysis. Erythrocytes burst en masse. Their debris clogs the smallest blood vessels and damages sensitive organs like the kidneys and brain.

In addition, erythrocytes are then missing to transport oxygen and haemoglobin becomes low. If people with G6PD deficiency get this HCQ-prophylaxis or therapy the symptoms will appear soon.

1-2 days after the start of such treatment a very severe clinical picture with weakness, dizziness, respiratory distress and signs of organ damage develops.

This may end in death if the toxic medication is not stopped immediately.

Could it be one reason for those cases where severe shortness of breath was observed without typical signs of pneumonia. It is a clinical picture "as if the patient suddenly was dropped out on top of the Himalayas", said one of the New York ICU- doctors.

Did any of the patients get Chloroquine shortly before? Did anyone care whether the patient could have G6PD-deficiency?

It fits well with some case reports that the acute symptoms improve spontaneously (If the dangerous medication is stopped) thanks to a rapid normalisation of the blood count.

Almost nobody seems to be aware, that in Sub-Saharan Africa, for example, hereditary G6PD deficiency is widespread (20-30% of the population).

But also in other countries, where malaria was or still is endemic, there is a high prevalence of G6PD deficiency.

G6PD deficiency must also be thought of in families with a migration background e.g. in Chicago, New York and elsewhere. African Americans represent 6 percent of the population, but nearly 40 percent of Covid-19 fatalities (5). But Johns Hopkins University only is warning not to use "Aspirin, certain antibiotics (which?), Fava beans and Moth balls" but does not mention chloroquine derivates! (6)

So using the questionable SARS-CoV-2 test as a trigger for treatment or prevention with dangerous drugs like HCQ may kill many, without any pandemic being in sight.

This genetic peculiarity is also common in Mediterranean countries and in all regions where malaria has occurred or is still occurring.

I write this, just to remind everyone who is in charge and I am very disappointed, that in many of the new studies with HCQ, people with the enzyme deficiency are not explicitly excluded (1).

1. https://covid-19.cochrane.org/?q=k(Hydroxychloroquine)&pn=1
2. https://www.voanews.com/science-health/coronavirus-outbreak/cameroon-beg...
3. https://www.g6pd.org/en/G6PDDeficiency/SafeUnsafe/DaEvitare_ISS-it
4. https://www.hopkinsmedicine.org/health/conditions-and-diseases/g6pd-gluc...
5. https://www.vox.com/coronavirus-covid19/2020/4/18/21226225/coronavirus-b...
6. https://www.hopkinsmedicine.org/health/conditions-and-diseases/g6pd-gluc...

Competing interests: No competing interests

20 April 2020
Wolfgang Wodarg
internal medicine-pneumology, public health
none
Berlin