Good news: Effective drugs and promising treatments for Covid-19 disease

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The rally to discover the cure for Covid-19 disease continues at a frantic pace. Dozens of companies have focused their efforts on rapid testing and development of effective drug therapy and vaccines. Optimism is pervasive, but so is uncertainty. Everyone recognizes that Corona SARS-COV 2 is a largely unpredictable adversary. Unpredictable, but not invincible.

But until the clinical trials of the new drugs are completed, experts are studying the effectiveness of the existing ones. Several commercially available formulations are being tested in the treatment of patients, as well as drug combinations. Of course, many of our fellow citizens were not satisfied with hearing the positive news, but rushed to the pharmacies to get specific preparations, creating shortages and endangering their lives, as these preparations have very serious side effects. Dimitris Kouvelas, a professor of Clinical Pharmacology and director of the AUTh Medical Laboratory of the same name, tells the inside story that the brand names of the products used in the treatment of patients with Covid-19 may not offer anything to the public. “What might help morally is the reference to the fact that there are some drugs that seem to work and we are not completely helpless.”

How close are we to effective drugs for Covid-19 disease?

As Theodoros Sklaviadis, director of the Pharmacology Laboratory of the Department of Pharmacy of the School of Health Sciences of the Aristotle University of Thessaloniki, explains in the inside story, the antiviral drugs available for pharmacological interventions are limited because they are difficult to access. That is why the most effective treatment for viruses before entering the body is vaccination, as the cells of our defense system produce antibodies that can inactivate viruses.

What we want to achieve with therapeutic approaches
“The virus is not a living being,” clinical pharmacology professor Dimitris Kouvelas told the inside story. “That is, it is a system of chemical molecules, a nuclear acid (genetic material) and a protein cover: the virus. Sodium has the ability to attach to some of the cells of our body (respiratory, immune, gastrointestinal, etc.) and to throw its genetic material into the cell. This genetic material then uses the cell’s mechanisms to multiply, and when the number of viruses reaches a critical point, the cell breaks down and the released viruses infect neighboring cells and so on. So the treatments are either aimed at preventing adhesion, or at inhibiting intracellular proliferation, or at blocking the cytokine cataract, which is a life-threatening condition. Today, various antiviral drugs of the first two categories are being tested, with relatively poor results. ”

Mr Sklaviadis points out that efforts to develop new antiviral drugs are not expected to yield reliable results any time soon. As the professor of Pharmacology tells us, the new specialized antiviral drugs will probably be available after the end of the current epidemic and will be useful in future outbreaks. “For this reason, well-known antiviral and immunomodulatory drugs are being used that have passed almost all clinical trials for other diseases and are now being tested for this particular epidemic.”

What the general public, who are rightly wondering about the availability and effectiveness of new drugs, also needs to be aware of is that special attention needs to be paid to disseminating specific information. “Because a lot is being said and heard about possible treatments, both the scientific community and the readers should check the validity of the sources of the information,” notes Mr. Sklaviadis. It recommends that you rely on sources based on documented studies and published in reputable scientific journals.

Didier Raoul’s “experiment” with chloroquine

It received special publicity in early March The announcement of the famous French infectious disease specialist Didier Raoul for the effectiveness of chloroquine in the treatment of patients with Covid-19. Although the sample of patients receiving this treatment was limited, the findings of the scientific team were quite promising. The therapists ‘reports speak of a significant drop in patients’ fever, improvement in CT scans, and higher rates of viral load negativity.

However, the announcement created a series of problems, as in several countries, including Greece, many rushed to procure the commercial preparation. The dilapidated condition led the EOF to the decision to administer this substance only with a doctor’s prescription. EOF President Dimitris Filippou stated that our country has already ordered five tons of the active substance in order to produce the drug in a domestic pharmaceutical industry. According to information, the production will be undertaken by h Uni-Ρharma, ensuring sufficient quantities of Unikinon for domestic use (approximately 24 million doses).

Scientific reactions for the use of this substance were expressed worldwide and especially in France, resulting in the rupture of Raoul’s relationship with Macron and the departure of the professor from the scientific team advising the French president to treat coronation. Opposition to the credibility of both Raoul’s new research and that of the scientist himself (who, due to controversial tactics, has been “excluded” from reputable scientific journals), continues to expressed publicly.

One interesting article of the specialized virologist Andre Calil on the clinical trials of drugs during a pandemic.

“THE hydroxychloroquine, which is a classic anticonvulsant drug, seems to help, but without understanding the exact mechanism and without being able to identify eligible patients, etc. ” tells us the professor of Clinical Pharmacology Dimitris Kouvelas. “It is being tested in combination with other drugs involved in protein synthesis or cell membrane function.” However, as he explains, these therapeutic efforts must be documented. “Drugs that bind inflammatory agents, such as antibodies, also provide significant help tosilizumab, which gives a significant percentage of survival to the seriously ill “.

In any case, Mr. Kouvelas recommends that their use be safe only if it is done by specialists and doctors familiar with the condition of each patient.

The antiviral that is already used in Greece

Recent clinical practice suggests that in addition to the anticholinergic drug chloroquine, satisfactory results against coronary heart disease it also has antiviral remdesivir (analog of adenosine nucleotide). As Mr. Sklaviadis explains to us, the first creates an incomplete genetic material of the virus and the second creates a complex with normal heme, which is very toxic to the particles of the new colon. However, Mr. Sklaviadis points out that clinical use can and should be made only in confirmed serious cases and in no case for precautionary reasons. The reason is that both drugs have a large number of side effects.

The antithetical remdesivir, which is used internationally for the treatment of patients in critical condition, it is now used in Greece. According to the infectious disease specialist Mr. Sypsas, it was used in patients both in Patras and in Athens. The pharmaceutical company Gilead, however, said it could not meet the demand due to the pandemic and would henceforth satisfy “remedial use” of remdesivir only for minors and pregnant women with severe symptoms. However, Gilead informed us that its use is experimental, as it is still in clinical trials, and they also warn of serious side effects such as liver damage. In total, six studies are evolving in areas with a high prevalence of Covid-19 disease in order to assess the safety and efficacy of the duration and dosage of remdesivir therapy.

Promising experimental treatments

Corresponding hopes were expressed and for favipiravir, a Japanese drug Toyama Chemical, which was used to treat new strains of seasonal flu (brand name Avigan), while it had been tested in patients with Ebola and Zika. A few days ago, China’s National Medicines Agency approved its extensive use after the “excellent results” found in the first extensive trial of 350 patients in Wuhan and Shenzhen. In the majority of patients, the virus ceased to be detected in their body within four days of starting treatment, and their lung condition was significantly restored (91% compared with 62% of those who did not receive treatment). Its tests are expected to continue outside of China to determine its effectiveness. According to information from inside story, sufficient quantities of favipiravir have also been ordered by the Greeks principles ..

Another promising drug treatment for HIV, Kaletra, did not perform as well as expected, as the first clinical study did not help the 199 patients with coronary artery disease who participated in it recover.

Doctors from China, however, say that The combination of lopinavir and ritonavir may have effects when administered to patients in the early stages of the disease.

International initiatives for faster steps
THE World Health Organisation announced the greater clinical study of the treatments being tested choosing the four most promising. The Solidarity program will test the following substances: remdesivir, hydroxychloroquine, lopinavor and ritonavir and interferon-beta.

At the same time, the European clinical trial Discovery with similar targets under the auspices of the National Institutes of Health of France (INSERM) with the aim of involving 3,200 COIVD-19 patients in several European countries.

The official recommendations to doctors in Greece

The combination of drugs now seems to be the choice of Greek doctors. In recent statements, Sotiris Tsiodras said that “we cannot afford to wait for monotherapy” and therefore combined treatments are already in place – with two, three or even four drugs depending on the severity of the patient’s condition. He even said that many patients in Greece who received double or triple treatment have already escaped the danger. “We hope to have better results than those published in monotherapy in other countries,” Mr Tsiodras said.

In a later statement, Mr. Tsiodras referred to an “important discovery” by the research team of the Center for Excellence in Drug Design and Discovery of EKPA, which he even described as “global originality”. In domestic hospitals, a single treatment protocol is now in place, which includes all drugs with proven or apparent efficacy. Its use is also included in this protocol colchicine, a well-known drug proposed by a team of Greek scientists as a cardioprotective, the effectiveness of which is expected to be further investigated in the context of the GRECCO-19 clinical trial (The Greek study in the Effects of Colchicine in Covid-19 complications prevention). In fact, for the first time, Mr. Tsiodras stated that care can be extended, following a medical instruction and prescription, to patients who are at home and have not necessarily undergone a diagnostic examination.

In addition, Sotiris Tsiodras stated that the members of the medical and nursing staff who treat patients with Covid-19 may, if they wish, receive special precautionary precaution for the next two to three months, based on a protocol to be announced.

As EODY officially informs us, the lack of sufficient clinical data does not allow a clear recommendation for the preference of specific drugs over others. The official instructions to the doctors of the domestic hospitals suggest specific drugs, depending on their availability: chloroquine phosphate (Aralen), hydroxychloroquine sulfate (Plaquenil), a combination of lopinavir / rhetoric tonamistavis epitaphiris (Kaletrara) (Kaletra), a combination of darou that we do not have enough clinical data, but there is in vitro data on antiviral activity. The instructions of EODY also mention the possible use of α-interferon by inhalation.

Promising treatments with a Greek stamp

The biotechnology company Regenerates works with Sanofi for his clinical trial Kevzara (sarilumabi) in patients treated with severe Covid-19 infection. This drug is used for patients with rheumatoid arthritis. According to Regeneron Vice President for Research Christos Kyratsous, the first indications from patient trials in China are positive, but the tests must be completed before their use can be extended. In the Chinese study of 21 patients with Covid-19 it was found that in total the fever was significantly reduced while in 15 of them the need for supplemental oxygen was reduced within a few days.

The clinical trial at medical centers in New York is expected to study about 400 patients with severe Covid-19 infection with the aim of studying Kevzara’s effect on fever and oxygen levels in patients and preventing premature death. George Giankopoulos, co-founder and CEO of Regeneron, explains that sariloumab is a human monoclonal antibody that inhibits the action of interleukin-6 (IL-6), which appears to be associated with pneumonia in patients with hyperactive inflammatory response. suffering from Covid-19.

But along with Kevzara’s clinical trial, Regeneron already testing a “cocktail” of multiple antibodies which will target both pre-exposure to SARS-CoV-2 virus exposure and Covid-19 disease treatment. According to Mr. Giankopoulos, they hope that the first tests on humans will take place in the summer. The cutting-edge technologies recruited by the US company, they have also been used in treatment proposals such as REGN-EB3, which has dramatically improved Ebola’s treatment tactics. If the effectiveness of this cocktail is clinically proven, the company is optimistic that it will be able to start clinical production immediately, targeting hundreds of thousands of precautionary doses per month by the end of the summer.

Caution!
As with all medications, patients should follow their doctor’s advice and obviously not take them without a prescription and explicit medical instruction. Especially for Kevzara, its manufacturing company informs us that it may cause serious side effects, such as severe bacterial infections, tuberculosis or even death, as it affects the immune system.
With the experience of dealing with Ebola

Switzerland’s Roche has also announced that it is working with the US Food and Drug Administration (FDA) for a randomized clinical trial of Phase III, which aims to assess the safety and efficacy of Actemra / RoActemra (tocilizumab) in the treatment of severe pneumonia caused by Covid-19. The drug with the active substance tosilizumab is used to treat adult patients with moderate to severe rheumatoid arthritis. It has already been tested in China, and 330 patients worldwide will receive it in the next clinical trial. And this substance acts as a competitor to interleukin-6 (IL-6) receptors, whose increased levels are associated with increased mortality in patients with pneumonia.

Medical assistance from Cuba

Cuba’s state-owned pharmaceutical industry recently guaranteed mass production of a drug based on the recombinant human interferon alpha 2b. The specific substance already used to fight other infections, but also hepatitis.

The substance has already been tested in China in combination with others, with satisfactory results and is now produced at the Changchun Heber Biological Technology plant in Jilin, China. It is intended to be used even as a preventive treatment for health personnel and high-risk individuals. So far it has been shown to be effective even in the early stages of infection.

Η Κούβα έχει δεσμευτεί για την ευρεία διαθεσιμότητα ιντερφερόνης. Σύμφωνα με δηλώσεις του γενικού διευθυντή της CIGB Ευλόγκιο Βάσκεθ, η κρατική φαρμακοβιομηχανία μπορεί να καλύψει τις τοπικές ανάγκες σε ορίζοντα εξαμήνου, αλλά και να εξαγάγει αρκετές ποσότητες για να ικανοποιήσει τη διεθνή ζήτηση – όπως αποκάλυψε, εκτός της Κίνας έχουν ήδη κατατεθεί επίσημα 15 αιτήσεις από άλλες χώρες.

Ελληνική startup επιστρατεύει την τεχνητή νοημοσύνη στη μάχη για τη θεραπεία
Η Causaly, μια ελληνική startup, αξιοποιεί την τεχνητή νοημοσύνη για την ανάλυση τεράστιων ποσοτήτων δεδομένων από τη διεθνή επιστημονική βιβλιογραφία προκειμένου να χαρτογραφήσει τις υφιστάμενες επιλογές θεραπείας. Το dataset που προέκυψε από την ανάλυση διατέθηκε ήδη στο Bill and Melinda Gates’ Global Health Drug Discovery Institute (GHDDI), ενώ μπορεί να διατεθεί σε ενδιαφερόμενα ιδρύματα και οργανισμούς (δωρεάν ανοικτή πρόσβαση για οποιαδήποτε μη εμπορική έρευνα). Συνολικά, εντόπισαν 90.000 συνδέσεις μεταξύ εγκεκριμένων φαρμάκων, πιθανών στόχων φαρμάκων και του νέου κορονοϊού. Όπως επισημαίνει ο Γιάννης Κιαχόπουλος, συνιδρυτής και CEO της Causaly, εντοπίστηκαν 131 ουσίες που δικαιολογούν περαιτέρω έρευνα.
Μπορεί να βοηθήσει το αίμα όσων έχουν αναρρώσει;

Μια υποσχόμενη θεραπεία, ειδικά για όσους νοσούν βαριά, βασίζεται στη χρήση ορού αίματος από ασθενείς που έχουν αναρρώσει, προκειμένου να λάβουν τα απαιτούμενα αντισώματα. Στην Κίνα ήδη από τις αρχές Φεβρουαρίου οι αρχές ζητούσαν από τους ιαθέντες να δώσουν πλάσμα προκειμένου να βοηθηθούν άλλους νοσούντες, ενώ και σε παλαιότερες επιδημίες (SARS, MERS) η τακτική είχε εφαρμοστεί με σχετική επιτυχία.

Στην Ελλάδα, η περίπλοκη διαδικασία της πλασμαφαίρεσης από όσους έχουν ανοσοποιηθεί από τον ιό θα καθοριστεί από ειδική ομάδα αιματολόγων στο Νοσοκομείο Αττικόν υπό την καθηγήτρια Βασιλική Παππά και τον Σωτήρη Παπαγεωργίου. Όπως πάντως διευκρίνισε ο κ. Τσιόδρας, η συγκεκριμένη επιλογή θα γίνεται μόνο για όσους διαπιστώνεται ότι τα φάρμακα δεν λειτουργούν.

Ο καθηγητής Κλινικής Φαρμακολογίας Δημήτρης Κούβελας επισημαίνει ότι όπως και με άλλους ορούς (αντιτετανικός, αντιλυσικός κ.λπ.), μπορεί να αποδώσει, αλλά χρειάζεται να καθαριστεί ουσιαστικά από τα αντιγόνα του δότη. «Τα αντιγόνα αυτά μπορεί να πυροδοτήσουν μια αντίδραση βαρύτερη από αυτήν που κάνει ο ίδιος ο ιός» σημειώνει ο κ. Κούβελας.

Δικαιούμαστε λοιπόν να αισιοδοξούμε; Undoubtedly. O κορυφαίος επιδημιολόγος Λάρι Μπρίλιαντ θεωρεί ότι η πανδημία θα ελεγχθεί – και με τη βοήθεια των αντιιικών φαρμάκων. «Έχω την ελπίδα ότι σύντομα θα έχουμε στη διάθεσή μας ένα αντιιικό για την Covid-19. Όχι μόνο για θεραπευτική χρήση, αλλά και για προφυλακτική». Ο Μπρίλιαντ επισημαίνει βέβαια ότι θα απαιτηθεί χρόνος για να διαπιστώσουμε με βεβαιότητα ποια φάρμακα είναι αποτελεσματικά και ποια όχι, και γι’ αυτό συστήνει υπομονή. Υπομονή λοιπόν.

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