“We believe that much of what we have learned from dengue is what should be done with COVID-19″
She has just been invited by the WHO as the only Latin American researcher to study societies suffering from the ravages of neglected tropical diseases such as dengue and Chagas disease, among others. In an exclusive interview with Infobae, held in Spain, she told us why she remains optimistic in the face of the new coronavirus.
It is clear that Silvia Gold’s passion as a renowned doctor in Biochemistry, internationally recognized for her great contribution to the study of the so called Neglected Tropical Diseases (NTDs), those that affect the most vulnerable sectors of society, such as Chagas and other mosquito-borne diseases like dengue, zika, chikungunya, and yellow fever, has “hardened her skin”, as they say in rural environments. And that passion has prepared her to face this global pandemic with sound scientific tools. For this reason, when it was time for clinical research, she knew which projects –which were already implemented with other pre-pandemic objectives– could be launched and/or targeted to find the cure for COVID-19.
Silvia Gold received Infobae in Madrid, Spain, where she is currently living, a city that is undergoing a new closure of borders due to the rise of infections and deaths, willing to discuss in depth the essential topics related to the management of this pandemic caused by the new coronavirus, SARS-CoV-2, in Argentina and worldwide. “We have made progress in the understanding of the disease, but it is still not enough. This completely new and disruptive situation for the entire world also generates social and political pressures, but the relationship between science and the emergency is neither easy nor linear”, Gold said to Infobae at the start of the interview.
Together with her husband, the medical doctor and businessman Hugo Sigman, Gold is co-founder of Grupo Insud and Insud Pharma, the international pharmaceutical branch. Partly due to previous experience and relying on talented and multidisciplinary local scientific groups, Insud has gained importance in this pandemic context. Based on public-private synergy, the group is conducting three late-stage research projects to combat COVID-19: the production of the Oxford-AstraZeneca vaccine for Latin America, and two clinical trials to gather evidence, hyperimmune equine sera and ivermectin.
Gold is also a member of the Uniting to Combat global partnership, whose goal is to eradicate neglected diseases in the world. Moreover, a few weeks ago she became a member of the board of the World Health Organization (WHO) Foundation and of the Harvard Kennedy School. It is a pleasure to interview Gold, since each of her answers is a lesson about scientific work. She is a strong supporter of public-private partnerships for the promotion of science in Argentina and is a generator of initiatives that provide society, especially the most vulnerable populations, with better health conditions.
–Silvia, the fact that now you are living in Madrid is a faithful testimony that the pandemic has not ended, but quite the opposite. This city has taken restrictive measures again due to the rise of infections. In turn, Argentina ranks between fifth and sixth among the countries with most infection cases per million population in the world. What is your opinion about the end of the pandemic?
-Silvia Gold: At the global level, we have been undergoing the pandemic for more than six months now. When the pandemic emerged, the earliest reagents did not work, the earliest therapeutic practices were not the best either; mortality rates were very high, which had to do with the lack of knowledge about the disease and the collapse of the health care systems. Moreover, at the beginning, the disease affected a given age group of the population that was vulnerable (elderly people, more than 70 years old). Today, mortality rate has definitively decreased. COVID-19 pandemic has transformed the world so deeply that everything will have to be rethought. It has had impacts on the economy, psychology, education. And, obviously, on health.
And the scenario is very complex because, on the one hand, there is an enormous production with a more open attitude from the scientific community. This is noticeable; works are shared and published very fast, and many funds have also been made available. On the other hand, this scenario is very novel, and is characterized by social and political pressure. Therefore, I think that sound common sense is necessary to deal with all this.
In a pandemic setting, it is necessary to act, since the pandemic is brutal, both in number of cases and in the mode of propagation; it is very contagious. There are many asymptomatic people, which multiplies contagions even more. In turn, the paralyzed economy generates tensions and social conflicts. We have learned something over this time.
–Considering the world scientific race against COVID-19, I would like to start talking about the vaccines (Editor’s note: at present there are six vaccine candidates in phase-3 trials, the last phase before being approved: the three from China, two developed by the state-owned company Sinopharm and one by the privately-owned Sinovac. Another one is being developed in the United Kingdom, at University of Oxford/ AstraZeneca. And the other two in the United States, one being developed by Pfizer-Biontech and the other by Moderna laboratory, in Massachusetts). How long will it take to have a COVID-19 vaccine? This is the most pressing question in the world. And which one will win the race against time and will put an end to the pandemic?
–Among the platforms of vaccine candidates in phase-3 trials, the most traditional approaches, the virus-based vaccines, either inactivated or attenuated, with something that stimulates the immune system, such as aluminium hydroxide, or whatever is used, are the so called classical vaccines, those developed by Pasteur and the subsequent ones, the ones that we all received. And my bet is on these ones because they are already tested (Editor’s note: these are the Chinese ones of Sinopharm and Sinovac, and the one developed by Oxford-AstraZeneca)
The mRNA-based vaccines are too novel and there are practically no vaccines approved. One of them is the one developed by Pfizer-Biontech. I consider that the Pfizer-Biontech vaccine faces a difficult challenge, the need for frozen storage. I find it difficult to imagine how a vaccine whose logistics requires temperatures so difficult to conserve will be massively administered. It may be better for low-scale vaccines, but I see it very difficult for massive scale. In this sense, it seems much easier to think of the AstraZeneca vaccine as of massive access, and it is also an innovative vaccine in terms of its technology.
Technically, the vaccine produced by the University of Oxford and that will be manufactured in Argentina is the one that gives us the most hope; besides, we know it very well because we are involved in it. Since its conception, this vaccine has been imbued with a concept that has to do with equity and access: it will cost not more than four dollars a dose and there is an agreement for its production in several countries. This is a condition imposed by Oxford: equitable distribution.
–What do you think of the scientific fast track situation that science is undergoing, a kind of emergency lever so that research works can respond rapidly and the unstoppable number of infections and deaths during this pandemic can be reduced?
-Reducing the times, both in the production and in the regulatory sectors, is right. But I also think that it is necessary to understand that pressures don’t help. One day, suddenly, the vaccine is “ready”, and the next day, it is interrupted due to side effects and it seems that we won’t have any vaccine at all. I think that neither situation is real. The side effects occur and are evaluated according to their impact in the clinical research, which in turn implies its own times.
The times can be shortened at the revision stages, and in this sense, regulatory agencies are cooperating in everything related to COVID-19; also in the times of production, which is what was planned with the AstraZeneca vaccine: a commitment to manufacturing doses even when they are not approved, because it means saving further time of production and distribution. It is difficult to deal with the general mood of society and the pressure on governors, which is huge; nevertheless, we are making progress especially in the understanding of the disease, and I think that we’re going to have a vaccine soon, as well as drugs.
– Let’s come back to the topic of access. Today, to put a true end to the pandemic –whether through vaccines, drugs or treatments– it is necessary to tackle the issue of democratization and access to the cure from the different sectors of health care systems. Do you also understand it this way?
-Absolutely. This virus is said to affect everyone equally, but that’s not true, since it affects more seriously those people that are in poorer conditions to protect from it. If one of the preventive measures is confinement, then it is much easier to comply with it when you live under comfortable conditions than under poor housing conditions. Therefore, I think that given the size of the number of inhabitants affected by coronavirus in the world, access is an essential issue.
Regarding drugs, the traditional clinical research methods are difficult to follow in times of pandemic. Health care systems are exceeded in their capacity, with physicians that find it difficult to perform clinical practices; there may be products that we consider good, but it is difficult to think of making placebo-controls with them; there is a lack of resources or the need to use only what is available. Hence, some flexibility is necessary. We don’t have to be dogmatic, we need to be flexible, understand the situations and offer opportunities, because not having opportunities to treat a patient or any hope to give is very hard.
–mAbxience will be the “scientific actor” of Grupo Insud that will produce the vaccine for the region; it also produces a protein within the frame of the research about hyperimmune equine serum. Do you think that a combination between any treatments and vaccines will be possible for the cure of COVID-19?
-Yes, that’s it. Before mAbxience participated in the regional production of the Oxford-AstraZeneca vaccine, it was involved in the project for hyperimmune equine serum along with the group leading this research, Inmunova. Because during the process of equine serum, a part of the protein that elicits most immunity is engineered at the laboratory in mAbxience. And horses are “challenged” with this protein to mount defence. Understanding that horses hyperproduce antibodies, that is how we reinforce our scientific idea of a passive therapy. Because antibodies injected through a serum (in this case, a horse serum) are definitively passive therapies. In contrast, vaccines “elicit” immunity, they train the body how to protect itself, whereas antibodies provide the solution. For this reason, thinking of combining them is not unreasonable.
It is a matter of timing; sera act faster but do not have memory. Vaccines trains your body, providing immunity. Therefore, what can indeed be combined is a therapy with sera and then a vaccine. In theory, the effect of therapy with sera is that the already infected person does not need a vaccine; however, all this is being studied, whether immunity lasts or not. It appears that it does last.
In mAbxience, when we started with this project of generating the protein for the hyperimmune equine serum, we also thought of making a vaccine based on this; however, any development takes a long time, and many human and economic resources. Therefore, we need to focus on what we think we will be available sooner and more timely.
Now let’s talk about another scientific study, which has been very promising so far, involving ivermectin, the antiparasitic drug for human use. This clinical trial involved 45 cases in Argentina and showed a potent antiviral effect. What is the status of ivermectin today as an antiviral drug to treat SARS-CoV-2 virus?
-I am particularly fan of ivermectin. It is a very valuable drug, with great therapeutic action, with a large window between action and toxicity, and we always think it is underused. While it is mostly used in the veterinary field, it could be more widely employed in the human field.
For years now, we (Editor’s note: Grupo Insud, Mundo Sano) have been working for the approval of an invermectin formulation for use in parasites –which is what we had typically done with the drug– in Europe. When we heard the news that it could have antiviral effects on SARS-CoV-2, we felt the challenge that we had to test it more deeply. So now we are going through the process of requalification of the ivermectin generic at the WHO, and registering different formulations. We are also working for its registration at the European Medicines Agency (EMA).
The clinical trial recently performed with ivermectin involved researchers from Conicet and received private funding as well as public funding from the Ministry of Science and Technology. The results are very interesting, since we found a reduction in the viral load associated with availability of invermectin in blood, with a clear concentration at which activity was detected; it was very meaningful that those reaching such blood concentration had a clear reduction in viral load.
This is very interesting, firstly because these results are the first rigorous data of viral load measurement in COVID-19 patients. But also because ivermectin was mentioned in other viral diseases and it has never been demonstrated in humans; and we think that it has to do with the dose. We think that ivermectin is a very promising tool, but it must be used correctly, it must be used at a high dose and, therefore, the quality of the product is very important. We hope that ivermectin can be soon prescribed for COVID-19.
Gold could well be awarded the honorary title of Lady of science in Argentina. And she deserves it for several reasons: those related to her successful scientific career as biochemist in the country, as researcher in NTDs or poverty-related diseases, a work pioneered by Gold by applying field and laboratory research.
– You have been recently invited by the World Health Organization to be a member of the board of the WHO Foundation; you are the only Latin American scientist that has been invited so far. Let me mention this in public because you keep a low profile and would not tell me…
-Yes, that’s true. This is the first time in its 70 years’ history that the WHO launches a foundation. COVID-19 pandemic accelerated the creation, which took place in May 2020 and is now being setting up. And, finally, in August this year they invited me to become a member of the board of the Foundation. It is really very gratifying, since in Mundo Sano our strategy has always been to generate evidence that contributes with public policies and the WHO is like the beacon of global health.
– In this context of general sanitary crisis, an issue that is often overlooked is the impact on the already called neglected diseases in the old normal, those that have always been left behind in public health priorities because most of the affected people belong to vulnerable, marginal social groups and lack political influence: the most widely known in Argentina is Chagas disease. How do you see this tension with this new world at present?
– The WHO has just developed the roadmap 2020-2030; we are in line with the WHO because we have always considered that international organizations are necessary, and now more than ever. The WHO is focusing the strategy on a transversal approach to different diseases, evidence and evidence-based policies, public-private cooperation, because we understand that it is the responsibility of the national states, but we are grateful for the availability of a space where we can contribute.
We consider it essential to have a transversal approach to diseases, since programs are very often valuable from a technical point of view, but they are not effective. We strongly believe in primary care attention, and that the medical doctor or health professional assisting the patient can think of all the diseases that the patient may have and that many of them can be easily tackled.
We also do a lot of work on dengue and on the consequent control of the transmission route: mosquitoes. Another aspect that we consider key at Mundo Sano is the work at the municipality scale, and, fortunately, this is much appreciated at present. We are conducting a mosquito monitoring program and we help those municipalities that may need it, we set the ovitraps, elaborate reports, and this is becoming a network.
Regarding Chagas, we are focused on the attention of the patient and on stopping mother-to-child transmission as a first step; we do not exclude anything, but at least if a baby is born with Chagas disease, we want to know it, and if no baby is born with Chagas disease, much better, because it means that we have treated the mother earlier. And the good news is that the treated mother does not transmit the disease! The effective moment of the treatment is when the patient is asymptomatic; it is an easy and inexpensive diagnosis, and if well treated, the disease is avoided. Argentina has got it.
– Thinking of the latter issue, the pandemic has made society have a proactive and central attitude towards public health, and society in a way has reconsidered the importance of social behaviour towards a disease. You had already come a long way focusing on prevention and the idea of “go and find the patients” with Neglected Tropical Diseases (NTDs), hadn’t you?
– Yes, exactly. The importance of public health, diagnosis, prevention. Much of what we have learned from dengue, we think is what should be done with COVID-19. We are conducting a very interesting program along with the University of Buenos Aries at the municipality of San Antonio de Areco; what we did was a kind of manual of epidemiology: define the tracking, isolate each contact rapidly, test everyone, and we have a very clear map and clear monitoring of how transmission behaves.