“Hydroxychloroquine and azithromycin taken together have a real chance of being one of the greatest breakthroughs in medical history. (…) Hopefully they will both be used immediately. People die, act quickly and God bless everyone.”
The lines come from the President of the United States, Donald Trump. He had announced a few days earlier that he saw huge potential in using hydroxychloroquine against Covid-19.
In the tweet Trump even added on Saturday: “H (hydroxychloroquine) works better with A (azithromycin), International Journal of Antimicrobial Agents.”
Hydroxychloroquine and the closely related Chloroquine are old active ingredients that are used against other diseases, especially against malaria and the autoimmune disease lupus. Following the announcement by Donald Trump, the demand for hydroxychloroquine has risen sharply in the United States. Patients with lupus report that they have problemsto get the tablets they need.
Azithromycin is an antibiotic, an active ingredient that primarily fights infections caused by bacteria.
Even before Trump spoke up at the weekend, the German infectious disease specialist Christian Drosten had warned against too much optimism with regard to chloroquine.
Success in the laboratory. But also in humans?
Experiments in cell cultures have long shown that chloroquine can slow down the replication of many viruses, but this is also possible with the new Sars-CoV-2 coronavirus. However, the fact that an agent works in a cell culture does not mean that it also helps infected people.
There are several reasons for this, as Drosten, an infectiologist at the Charité in Berlin, explains. One of them is that the agent in the body would first have to make its way to the lungs, where the coronavirus can do enormous damage. Another is that infected cells often only change the ingredients of medicines before they take effect. It is very uncertain whether cells in the body react in the same way as cells in a petri dish.
With hydroxychloroquine as an active ingredient against Covid-19, scientists seem to be going one step further. In France, doctors tested the drug on a small group of Covid 19 patients. The study has not yet been published, but circulates on the Internet. At first glance, the results look promising. However, Drosten has considerable doubts about the validity of the investigation.
“Unfortunately there are several things in this study where you have to discuss whether you can do it that way,” he said to the NDR.
Similar result to that of a headache tablet
For the study, the medical team from Marseille treated 26 Covid-19 patients with the malaria drug, 16 Covid-19 patients served as a control group and received no medication. In the group with the agent, the concentration of the coronavirus in the throat dropped faster than without the agent, the conclusion is. Six patients from the drug group also received the antibiotic azithromycin to avoid simultaneous infection with bacteria. The measured effects were particularly strong for them.
However, there are many indications that the patients in the medication group were included in the study at a later stage in the illness than the patients without medication. Then it is part of the normal course of the disease that the concentration of the viruses in the throat drops again. This usually happens within ten days of the onset of the disease, says Drosten.
“After that, the virus is very little or very irregularly detectable in many patients in the throat,” explains the virologist. But that has nothing to do with how the virus behaves in the lungs, where it can cause serious damage. “Perhaps the study would have been the same if the patients had been composed in this way, but they had not been given chloroquine, but a headache pill,” says Drosten.
Another of several shortcomings of the study: The researchers only evaluated the data from 20 participants out of the initially 26 people in the medication group; in six of them, they had to stop giving medication. This was necessary for three participants because they had to go to the intensive care unit – despite the medication. The doctors did not include their results in the final evaluation.
The virologist says that he does not want to say that chloroquine does not work. “I just want to say: We are not a bit smarter the way this study was done.” Instead, he calls for examinations that do not analyze the virus concentration, but the actual state of health of the treated patient.
WHO starts worldwide, unbureaucratic drug trials
It is clear that it must be clarified as soon as possible whether hydroxychloroquine – and other active ingredients – really help against Covid-19 or not. The World Health Organization (WHO) announced the start of the so-called Solidarity Trial last week: Doctors worldwide can take part in the planned large-scale study with as little red tape as possible.
The study will initially test four drugs or drug combinations, although it should be possible to add to the list:
Chloroquine, the original antimalarial agent from which hydroxychloroquine is derived
Remdesivir, an antiviral that was first developed to treat Ebola
Lopinavir and ritonavir, given in combination for HIV infection
Lopinavir and ritonavir supplemented with interferon beta
These drugs are also used in a European study tested in which hydroxychloroquine is to be used. The WHO originally did not want to include hydroxychloroquine and chloroquine in the solidarity trial. Because of the great attention to the funds, the organization changed its mind, writes the science magazine “Science”.
Trump himself called for a press conference to use hydroxychloroquine immediately. “What do we have to lose?” He asked. The answer is simple: In addition to patients with lupus who may no longer be on medication, as with almost any medication, all ingestors risk side effects.
Even though hydroxychloroquine is generally well tolerated, it can in rare cases lead to retinal changes, restlessness, sleep disorders and gastrointestinal complaints. This risk is only worthwhile if Covid-19 patients really benefit from the intake.