Covid-19 outbreak was discussed in an interview with Dr Levent Alparslan, President of Pharmaceutical Technology Department of Istinye University Faculty of Pharmacy, by Winally.
W- The epidemic started in China and spread all over the world. Now, while China takes control, the world is dealing with an epidemic. Can we say that other countries were caught off guard in this regard?
L.A.- It is possible to say that the world was caught unprepared for the COVID-19 virus, which started in Wuhan, China in January, and spread rapidly all over the world, creating a pandemic. The main reason for this is that very healthy and reliable information does not come from China. I think that the fact that the mortality rates and numbers are low compared to the general population of the country and superiority against the previous corona viruses is misleading the public. It is possible to reach these numbers with influenza disease every year. Therefore, it was not necessary to take special precautions about extraordinary measures before the virus spread to the countries. Although the Chinese administration was successful in combating the epidemic afterwards, we can say that the numbers it shared remained in the focus of common criticism in terms of reliability and timing.
W- Has therapeutic drug been developed for COVID19? What stage is the world in drug development?
L.A.- A known drug or vaccine of COVID19 is currently not available. However, since there is no immediate drug development in the extraordinary conditions we live in, medicines used in similar treatment practices with successful results is being used. Numerous clinical trials are being recorded to treat COVID-19. First, various drugs designed for other diseases such as Ebola, HIV, malaria and arthritis have begun to be applied. These drugs are not expected to achieve 100% success in the disease. However, positive effects have emerged in inpatient and intensive care processes. Medicines used to support can be included in the treatment protocols to shorten the length of hospital stay, release the ventilators and ultimately improve the condition of patients with COVID-19, bringing great relief to their healthcare system.
W- What can be said about the effect of antiviral drugs developed before on treatment? Are there any antiviral drugs that show high efficacy against COVID19?
L.A.- The multicenter and multinational clinical study currently undergoing the Phase 3 study (with target 1000-3000 volunteers) investigates the safety and efficacy of the active ingredient Remdesivir. Remdesivir is an antiviral drug first developed in 2009 for HIV and hepatitis C treatments. The efficacy against MERS and SARS viral pathogens that are structurally similar to COVID-19 has been studied with invitro and in vivo animal models, therefore it is thought to be potentially effective against COVID-19. It is clinically compared to their efficacy in moderate to severe disease status, placebo (i.e. comparison to drug-free therapy) and other treatment practices. If the phase 3 is successful at the end, there is a possibility that this drug will be licensed and placed on the market for COVID19.
Another antiviral drug that has been tried against COVID19 is Avigan, developed in Japan. Avigan, a broad-spectrum antiviral drug used in the treatment of flu, has been among the treatment practices in China. In a study conducted in China, it was stated that it performed better than another flu drug called Arbidol. It is difficult to say that there is enough data in the studies. It has also been reported that the drug has side effects that cause kidney damage. Several ongoing studies in China are expected to be completed at the end of April or May. The clinical studies of this drug against COVID19 are at the Phase 2 and Phase 3 levels. Arbidiol failed against COVID19.
Kaletra, another HIV drug, was approved in 2000. It is a combination of two active ingredients consisting of lopinavir and ritonavir. It is thought that Kaletra can reduce the viral load of the disease in patients with COVID19. Unfortunately, it was not effective at the end of clinical studies.
Other antiviral drugs that have been successful in clinical trials and treatment protocols are chloroquine and hydroxychloroquine. Hydroxychloroquine, first approved in 1955, is the most widely used version of chloroquine, an anti-malaria drug for a long time. It is approved as a generic drug for the treatment of arthritis and lupus. Laboratory tests have shown that hydroxychloroquine has a slightly better potential against SARS-CoV-2 than chloroquine. Hydroxychloroquine has also been widely used in China and South Korea in the fight against COVID-19, the drug has been added to the treatment guidelines in both countries. In some studies, conducted in France, clinical studies have been carried out with significant results in COVID-19 patients. Hydroxychloroquine has been proposed with an antibacterial drug, azithromycin, as an application that appears to speed up the time it takes patients to overcome the virus. It is produced and used as domestic production in the treatment process in our country.
W- Is it possible to say that these drugs are absolutely successful in treatment? Are other antiviral drugs also used? Do these drugs have side effects?
L.A.- Considering the studies published so far, it is seen that more clinical studies are needed to define the success of these drugs. The data at hand are not at a sufficient level statistically. By comparing the data obtained at the end of the Phase 2 and Phase 3 studies with the information from different points of the world, it will become more clear. Other antiviral drugs are also being tried. For example, ivermectin, which is also used in the treatment of parasites and scabies, has been found effective in some studies. As a result of the fact that efficacy and safety studies against COVID are supported by clinical studies, drugs can be released on a licensed basis. It is not possible to say that even if the drugs used for instant and trial purposes respond to the treatment, they are 100% effective. In clinical evaluations, we can say that side effects and serious symptoms are reported. These symptoms are recorded. From time to time, changes are also made in treatment protocols. In summary; It is possible to say that important information was obtained in a short time, but I think it should not be overlooked that the information can be updated and varied.
W- Are there other treatment applications for improvement? Can you give examples of drugs used together against COVID19 in the world?
In the fight against L.A.- COVID19, some mechanisms in the body's natural balance have gained importance. Interleukin-6 is a signaling mechanism that the human body makes as an immune response to an infection. According to data from China, it has been suggested that blocking this mechanism may help patients with COVID-19, even if it does not come from a randomized controlled trial. In particular, it has been evaluated that it may help alleviate the inflammatory response in the lungs of patients with difficulty breathing. Kevzara and Actemra drugs are anti-inflammatory drugs used to alleviate the symptoms of COVID19 disease instead of antiviral effects. Kevzara and Actemra are Interleukin-6 (IL-6) inhibitors in the same therapeutic class. While antiviral drugs target the virus more directly, these IL-6 inhibitors have been shown to be able to alleviate some of the severe symptoms of COVID-19. The effectiveness of these drugs in treatment continues at Phase 2 and 3 levels. The efficacy of immunomodulators and their association with cytokine release mechanisms are also investigated.
Another treatment method that we have important expectations is plasma therapy. The antibodies are produced and transported to the patient from the plasma of people who have recovered. In our country, this method has started to be used. Studies are ongoing in various countries on the therapeutic efficacy of Convalescent plasma.
Stem cell studies have also gained attention for COVID19 treatment. The available data are not yet sufficient to provide a definitive solution.
W- What do you think about the people who do not know whether they are ill but who are in doubt, and want to use the malaria medicines that are heard recently for prevention or treatment?
L.A. - I was asked this issue frequently. We talked to our pharmacist friends that there was a lot of demand. First of all, no drugs are currently preventing the transmission of the virus. This point is important. Therefore, I do not recommend anyone to use preventive drugs. In addition, I think that even if there is an infection condition, it is necessary to diagnose with kits and use medication if necessary, under the control of the doctor. Antiviral drugs used in diseases such as malaria and hepatitis are not innocent drugs and can have serious side effects. Therefore, they should be used with the advice of a doctor and if necessary.
W- When do you think vaccination studies end? Does the fate of all humanity depend on these vaccines?
L.A.- Since effective protection against disease will be provided with vaccines, safe and effective vaccine development studies have been initiated rapidly in various parts of the world, including in our country. It normally takes years to develop a vaccine, but there is an emergency. Therefore, with the mobilization of all opportunities, assumptions are made that a new vaccine may emerge in a short time. The important point here is, the developed vaccine can be successful in treatment and can be used according to urgency, but adequate tests and clinical studies must be performed before obtaining a license. Currently, there are 6 vaccine studies that are in Phase 2-3 trials.
Clinical efficacy and safety studies have been initiated with the BCG vaccine also giving positive results in the treatment of COVID-19. I hope that vaccination studies in our country will also be successful.
In another important study, the mRNA-1273 sequence, the corona virus vaccine, was completed after the Chinese authorities shared the genetic sequence of the corona virus. It is thought that data on the safety and immunogenicity of mRNA-1273 will be obtained rapidly in the Phase 1 study in the USA.
W- It was discussed that some drugs should not be used in patients with infection to use them as pain relievers. Are there any drugs that should not be taken?
L.A.- We can follow these issues through scientific data and clinical studies. Currently, scientific statements say that there is insufficient evidence that nonsteroidal anti-inflammatory pain relievers affect the course of patients in COVID19 patients. I think additional data is needed to make a clear statement.
W- What can you say that is promising in the period when the whole world is mobilizing and we have had extraordinary times?
L.A.- As you said, the whole world is going through an extraordinary period. In the time period when communication knows no boundaries, we experience the first historical period when we feel the same things and fight against a common enemy. So I think we realized that we live on the same planet. First of all, we are living in a period when the instinct of unity and cooperation in local, national and international dimensions has increased. we know the enemy; I am sure it will be overcome. Intense efforts are being made all over the world to prevent the epidemic, the effect of which is outside the health framework. In our country, valuable scientists of our universities, and our companies show great efforts. The support of our government is very important in this regard. I believe that if citizens comply with the measures, the disease will be brought under control. In this mobilization, we are grateful to all healthcare professionals, pharmacists and scientists at the forefront.
I wish God's mercy to my colleagues whom we lost in this struggle. We will never lose hope, and not stop taking precautions. Stay healthy.