Belgium revisits: Hydrochloroquine has indeed been shown to decrease the production of pro-inflammatory cytokines, both ex vivo and in a pulmonary model.

TRANSLATED

Source: le journal du medecin by Frédéric Soumois

A retrospective study published in the International Journal of Antimicrobial Agents examined the effect of hydroxychloroquine given to thousands of Belgian patients from March to May. The group that received hydroxychloroquine saw their mortality reduced by a third! But the researchers’ conclusion is clear: the product is a good anti-inflammatory, but has no antiviral effect, writes Soumois.

On March 13, hydroxychloroquine is recommended for any patient hospitalized because of Covid-19 and put on oxygen. Thousands of patients, often elderly (two thirds are over 65), then receive a fairly low dose of the product, comparable to what was given as a prophylaxis against malaria in the 1970s and 1980s, for five days.

Ten weeks later, the aura of hydroxychloroquine has been tainted. It has been suggested that is was not the desired miracle product.

Practitioners have been encouraged to give it less and less, then not at all. To be sure, Sciensano, the Belgian Public Health Institute is starting a retrospective study to assess its effect on patients. As of May 24, Sciensano’s database contains 15,544 patient cases from 109 Belgian hospitals.

Overall, participants were critically ill with over 80% radiologic pneumonia, large proportions with severe laboratory parameters including severe hypoxemia, and 5% requiring immediate admission to an intensive care unit (ICU). The median time from onset of symptoms to diagnosis of Covid-19 was five days. Compared to survivors, non-survivors were older, more likely to be men, and to have pre-existing illnesses. In addition, they more often exhibited biological markers of severity such as elevated levels of lactate dehydrogenase (LDH> 350 IU / L) and C-reactive protein (CRP> 150 mg / L), and severe hypoxemia (paO2 < 60 mmHg). The time between Symptom onset and diagnosis was shorter in non-survivors (median 3 days, versus 6 days in survivors, p <0.0001). The length of hospital stay was similar.

One-third fewer deaths

Patients in the HCQ group were younger and the male gender was predominant. Several comorbidities were significantly less frequent in the HCQ group, including cardiovascular disease, arterial hypertension, chronic renal failure, neurological and cognitive disorders, solid cancer, obesity as well as the proportion of active smokers. On the other hand, on admission, the patients in the HCQ group seemed sicker, as evidenced by the higher frequency of radiological pneumonia, acute respiratory distress syndrome, transfer to an ICU within 24 hours of admission and assistance. in invasive ventilation as well as the higher frequency of elevated LDH and CRP levels.

Study result: Hydroxy 2,400 mg over five days was “independently associated with a lower hospital mortality rate than patients treated with supportive care alone, even after adjusting for age, major comorbidities and the severity of the disease on admission “. Importantly, mortality was reduced regardless of the time between onset of symptoms and diagnosis and start of treatment.

The reduction in mortality and disease severity with HCQ is impressive

The reduction in mortality and disease severity is impressive: on average, 22% of these patients died. But while more than one in four patients (27.1%) who had not received the hydroxy died, the case fatality rate was only 17.7% among those who received the drug. That is to say a third of deaths less among those who received hydroxychloroquine.

From what to conclude to causality? No. To the association, certainly. 

“Our study provides further support for the claim that hydroxy is not associated with a short-term increased risk of cardiotoxicity and in-hospital mortality.

As of June 17, the Federal Agency for Medicines and Products health department recorded a total of 8 reports of adverse reactions suspected to be associated with its use for the treatment of Covid-19 in Belgium, including 3 cases of cardiac toxicity (all having received concomitant drugs) and no deaths reported ” , explains Dr Nicolas Dauby , specialist in infectious diseases at St-Pierre University Hospital (ULB).

Frédéric Soumois

“An association, not a causality”

“Our study is not a clinical trial, which compares two arms of patients who are completely identical, except that they are given a placebo or the real molecule. A study like this is the only one that could have established a causal relationship. . And there will not be, since hydroxy has no antiviral activity “, clearly slices Dr. Nicolas Dauby , specialist in infectious diseases at St-Pierre University Hospital (ULB) and researcher qualified in immunology of vaccination (FNRS).“Our study is based on standardized reporting forms during the most critical phase of the epidemic in Belgium. The cohort was established as part of continuous surveillance which aims to monitor the epidemic and identify the factors of risk of severe Covid-19 and unfavorable outcome. “

What bring an association between taking hydroxy and a reduction in severity and mortality, but insufficient to achieve causality. “Remember that our recommendation in March was based on in vitro observations. In vitro, hydroxy attacks the Covid virus. But in vivo, in animals and particularly in humans, the product does not no antiviral effect. This is fairly clearly established by a study which was carried out while our research was in the process of being published. The results of the Recovery trial showed no clinical benefit (death or discharge) in the hydroxychloroquine arm at a high dose (9200 mg in total over 10 days) compared to usual inpatient care. “

Conclusion? “Most likely, hydroxychloroquine has excellent anti-inflammatory activity. Clinical efficacy, however, could be mediated by immunomodulatory mechanisms, preventing progression to severe disease with over-inflammatory responses by dampening the infamous cytokine storm. “, explains Doctor Dauby“Hydrochloroquine has indeed been shown to decrease the production of pro-inflammatory cytokines, both ex vivo and in a pulmonary model. On a related note, the use of low dose dexamethasone has recently has been reported to significantly decrease the mortality of Covid-19 patients requiring oxygen. In addition, it has been suggested that the product has certain anticoagulant properties which may be beneficial in preventing thrombotic events in addition to low weight heparin molecular “.

https://doi.org/10.1016/j.ijantimicag.2020.106144

Illustration : Professor Dider Raoult leaves the National Assembly in Paris, France, June 24, 2020. The French doctor and virologist, whose use of hydroxychloroquine, a drug against malaria, in the treatment of Covid-19 has aroused attention and controversy around the world, was to answer questions from a parliamentary commission to investigate France’s response to the epidemic.

Related:

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