At what point is the search for coronavirus therapies (with some setbacks)

After the first few months of managing the emergency, some doubts begin to arise about some of the therapies initially considered promising.

the plasma of healed people, theozone therapyme vaccinesthe antiviral, monoclonal antibodies, the antimalarials. The list of treatments, potentially therapeutic or preventive, that are studied against coronavirus is very long and extends practically throughout the world, and most of the studies focus on China, Europe and North America (here, here and here some of the maps that take stock of ongoing trials). against Covid-19 we don’t have a treatment specific not a vaccine (And if we have it, it will not be before next year, probably, even if there are those who are already betting next September), and for now the most effective strategy available is still that of prevention (and the area of ​​infection) instead of treatment, limited to support therapies and to the administration of unlabelled medications. In front of therapy, along with promising studies and clues, after the beginning of the first experiments, the first setbacks begin to arrive. Or rather: just signs of normal search progress, as you might expect. They talk about uncertaintyof inconclusive data and of things we don’t know, like most all aspects of the new coronavirus.

Not yet a treatment protocol, but experience

That there is nobody therapy Coronavirus experts chorused it, experts meeting online on April 28 to assess what we know so far about coronavirus treatments, within the consensus conference organized by Healthcare Motor about its therapies. There is currently no safe and effective drug against Covid-9, he summarized. Massimo Andreoni, director of the UOC infectious diseases at the Tor Vergata Polyclinic in Rome: “We have many drugs tested, but the results obtained, in vitro, in vivo or in humans, cannot be considered definitive. All the experiments with Covid-19 suffer some bias and currently there are no convincing and definitive answers on the subject”. the drugs used right now added Francesco Menichetti, director of Uo Infectious Diseases Aou Pisana, I am medicines with other indications: “Against Covid-19 so far no therapy has shown any efficacy, we do not have sufficient evidence. In the absence of these, we proceed on an empirical basis, without the comfort that comes from rigorous number and drawing studies.”.

This does not mean that nothing exists promising, but rather, once again, that we are currently referring to a set of therapies for which there is no solid evidence: “We are not working and proceeding in honor of the principles of evidence medicine as we would in times of peace, because we are not in times of peace – commented Pierluigi Lopalco, epidemiologist at the University of Pisa and scientific coordinator of the working group of the Puglia region – This does not mean that we proceed anecdotally, even in an emergency situation we can adopt methodologies to collect so much evidence that we must treasure “. Hoping that the studies respond better, it is not always easy to continue in a situation like today. Thanks also to the support ofAIFA, which collect evidence of efficacy and safety for the treatments used against Covid-19 and the therapeutic guidelines. And considering that, along with doubts, about therapies, but more appropriately about patient management, clinical experience seems to have progressed in recent months, experts shyly admit, for example, with respect to ventilation and oxygen therapy, the use of heparins, anti-inflammatories or antibiotics against bacterial superinfections.

Doubts about antivirals

Within this context, in the absence of specific therapies, with medications used off-label and taken from other indications, used compassionately or reserved for clinical trials, some data are beginning to reach some therapies that question them, although indefinitely, potential use. This is the case, for example, with remdesivir, a proven antiviral also in italy, which has long been mentioned as a possible treatment for Covid-19. In recent days, however, its potential in fighting coronavirus it was partially reduced after the publication of a draft related to the results of a trial conducted in China. The draft – report tutor – would have been published in the database clinical trials by the World Health Organization, by mistake. These would have been results not yet reviewed, the WHO explained. Results that would not show benefits when using the drug against Covid-19: neither as recovery time from the disease nor as mortality rate (14% in the group being treated compared to 13% of the controls). And with side effects that would have led to discontinue treatment in approximately 11% of patients.

The same pharmaceutical company that produced the drug, Gilead, also intervened in the case, as in one note had specified how the accidental leakage of the study results was flawed by one “Inappropriate Study Description”. And again: “The study ended early due to low enrollment and consequently weakens to allow us to extrapolate meaningful conclusions. Therefore, the study results are inconclusive, although “ – read the note again – “some trends in the data suggest a potential benefit for remdesivir, especially among sick patients treated early “. At the moment, therefore, whether or not it is effective to reduce, it is impossible to say for sure, it will be possible to obtain more clues from other ongoing studies, explained by the pharmacist.

Because there are many studies underway on the drug – at least a dozen, searching the clinical trial databases. Some compare the drug with a placebo, others instead with other experimental treatments, such as lopinavir + ritonavir and interferon, others antivirals or even against antimalarials chloroquine and hydroxychloroquine. But, at least from some of these, the information that could be extracted is limited, warn some experts from the pages of Statistical News, pointing the finger at the very nature of the experimentations, which in some cases lack a control arm.

But we keep waitingantiviral. In fact, the announcement that came a few hours ago National Institutes of Health of the first results of a clinical trial (randomized and double blind) showing how remdesivir reduce recovery time from illness and the rate of mortality compared to placebo (11 days versus 15 and 8% versus 11.6% respectively). The results were received with enthusiasm, to the point that according to the American press the Food and Drug Administration would already be considering possible use in how emergency medication.

Also for lopinavir + ritonavir We still know little and, in fact, the news from the investigation is not always encouraging. Only last week, for example, the results of one were published study who, also in China, had tested the effectiveness of lopinavir / ritonavir or umifenovir (a flu medicine marketed in Russia) on a small sample. The results showed that, compared to supportive therapy alone, there are no clinical benefits of administering the drugs in mild and moderate cases of Covid-19, nor have they been able to shorten negative infection times. In addition, the researchers explain, patients treated with lopinavir / ritonavir they got worse than the others. The hypothesis presented by the study authors is that perhaps higher doses of the drugs are needed to observe efficacy, even if even on this front we must proceed with extreme caution given the presence of side effects. However, this is not the first time that the potential related to the use of lopinavir / ritonavir against Covid-19, which had not been shown to be effective, has been questioned. against severe forms of the disease Also in this case, however, the ongoing studies are many.

Antimalarial drugs

Also in antimalarial drugs, such ashydroxychloroquine, which for example had aroused the enthusiasm of the American president by saying that the line is that of caution. The current address in Italy allows its use at home and hospital, but a drug with proven safety and efficacy against Covid-19 has not yet been mentioned. So much so that from Aifa, they remember: “Since the therapeutic use of hydroxychloroquine is entering clinical practice based on incomplete evidence, a randomized trial evaluating its clinical efficacy is urgent.”. In addition to its use a prophylactic purpose should be reserved for clinical trials only, continue from the agency. That the evidence is incomplete is also the experience that suggests it in some cases, as he admitted during the consensus conference, for example Matteo Bassetti, Director of the Clinical Operational Unit for Infectious Diseases of the San Martino Polyclinic Hospital in Genoa: “Compared to a month ago, when enthusiasm for this drug was greatest, we are now more reluctant to use it, if not within clinical protocols.”. Even from abroad, the Food and Drug Administration itself recommends its use only at the hospital level or only in the context of clinical trials, warning against side effects such as heart problems.