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When you get an international scholarship as visible as that of the Chan Zuckerberg Foundation (the pediatrician who is the wife of the founder of Facebook), it usually stops and is celebrated. But the red eyes of Henrique Veiga-Fernandes and his team at the Champalimaud Institute show that this time, this is not what will happen: there is a lot of work in the emergency against covid-19, there is no time for celebrations.
Since the beginning of the disease, the co-director of Champalimaud Research has been practically dedicated to covid-19. And its immunophysiology laboratory is mainly testing, viral and serological. For the staff and patients of the center: their sensitivity, being cancer patients, requires that the space be “greedy freeAnd in three more external studies: the population in risk professions in Loulé, and the health personnel of the Hospital de Santa María, in Lisbon, and Santo António, in Porto.
The combination of the two tests, viral and antibody, in addition to having a practical objective of fighting the spread of the disease, will allow you to know more about it. That is, about what we do not yet know and that has a lot to do with being recent and, according to Henrique, “four out of five cases are asymptomatic.”
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The Chan Zuckerberg Foundation award is yet another demonstration of the importance of the work of Henrique Veiga-Fernandes and the Champalimaud Foundation in research work, as the name of the center says, in “Unknown”. And it is the second, along the same lines, and also by another pioneer from Silicon Valley: It was the 1.5 million that Henrique earned from the Paul Allen Foundation (from the Microsoft co-founder) that allowed him to start the study that showed the connections between the Nervous System and the Immune System, never before demonstrated.
Innovative technology made in Portugal
“We realized that the nervous system gives very specific instructions to the immune system,” explains Henrique. “It works as a kind of interface, it realizes the outside world and gives these instructions: look, do this, act.” To understand that this was the case, the Henrique Veiga-Fernandes team developed a super innovative technology and “totally made in portugal“with the appropriate name: Kiss or kiss. This technology allows us to mark and” study the relationship between neurons, the nervous system and immune cells, and how these two systems “kiss” and interact in the lung. “
Objective? “Promote more efficient responses of the body against infections”. Also, identify totally innovative classes of molecules for new cures for various diseases. The scope of this research is phenomenal. It can have results in diseases involving the immune system, as diverse as autism, diabetes, metabolism, infection, cancer, chronic inflammation … “The identification of new classes of drugs is transformative,” says Henrique, visibly hopeful. “It may not be the solution for everything, but at least it will open up our horizons.”
That’s why the Seattle-based Chan Zuckerberg Foundation looked at this little corner by the Tagus. “Because they reward the pioneering efforts that will open territory never walked before. The” unknown “, we are tuned. It is not innovative in something that is already known, it is what is not known, what is not known,” says Henrique.
This Champalimaud Institute award was won in association with researchers Isaac Chiu and Stephen Liberles, both from Harvard Medical School, the first specialist in neuroimmunology and investigates the interaction between neurons and immune cells in the lungs and skin, and the second focused on neuroscience, particularly “how the nervous system can detect what is happening in internal organs, such as the intestine “.
A world without disease.
The mission of Zuckerberg and his wife, a pediatrician by profession, is “to eliminate all the diseases of the world in the lives of our children”, which they consider realistic by 2100 … Let’s see. But in the meantime, there are new diseases to know and treat, as demonstrated by covid-19. The further the investigation, the further back, the faster you can fight, later.
In other words, having nothing to do with covid-19, this research by the Champalimaud Institute can also be decisive in this disease. “The new coronavirus has a high ability to infect nerve cells,” says Henrique. “Decoding how lung neurons instruct immune cells during viral infection will provide valuable information on how these two systems can cooperate to fight lung infection.”
The three studies that the Champalimaud Institute is developing can help, for now, to a faster and more concrete knowledge. They combine epidemiology, the study of disease, and immunology, the study of immunity to disease. That is why they combine the two tests: the virological, which works well to see if someone is sick, and the immunological, to find out if someone has been in contact with the virus and has developed antibodies against it.
Two tests against covid-19
“The use of both tests: diagnostic, useful in the first week, and serological tests, allows us to extend the time in which we have sensitivity to detect the disease. There is a lot of information that can be obtained from serological tests,” explains the researcher. . “Because four out of five patients are asymptomatic, and as such with diagnostic tests, we will never catch this part of the population. Having no symptoms, they do not go to a medical center and it is very difficult to have accurate numbers” .
Better numbers can lead to better decisions, namely policies, which are urgent at this stage of reopening. Leonor Beleza, president of the Champalimaud Foundation, participates in the technical committee that meets every Tuesday to advise the government and the president on the measures to be taken. “Not being our vocation, in this emergency situation it was a bet, either by research or by the administration, to make a contribution to society. We are setting the example and we were the first to put the evidence on the table. Now other institutions too Fortunately, because the Foundation, by itself, will do nothing, “says the researcher.
As an example, what the foundation does to its own employees and patients. Everyone is tested at the entrance to see the fever. Then, if there are signs, they are tested, and also before interventions and treatments. The equipment, which works in the mirror, is tested before the 15-day periods when they enter service.
Otherwise, there is social distance, masks and a lot of disinfecting liquid. “But this, of course, can only work because we have the ability to do tests quickly and at home,” explains Henrique. However, it was a significant investment to “continue to function and serve patients.” A virological test, at market prices, exceeds one hundred euros. An immune test will be around 40.
In the case of the tests in the municipality of Loulé, 1235 risky workers, from journalists to cleaning officials at the City Hall, a local collection infrastructure was installed next to the stadium, where people carry out the procedures without leaving the car . The tests are fast, run between half an hour and three hours (“only in this way are they operational”) and result in better equipment management and the now-called “return to normality”. Science at the service of society, in the purest example.
And the investigation? The treatment of all the information will be integrated into the work of the Champalimaud Foundation that revolves around the two areas: neuroscience and cancer. “There is an important part of cancer research today, and we are now beginning to understand by neuroscience what the immune system contributed to these types of diseases. And in that understanding we have long known the importance of responses to viruses like this It is the subject we have studied, and now with a different perspective because there is a very significant proportion of patients who end up dying of covid with an unregulated immune response, an exaggerated immunopathology is the cytokine storm There is such an exacerbated activation of the immune system that the person ends up dying of his own cure. “
Know what you don’t know you don’t know. Begins to suspect. And advance through the unknown outside. In response to covid-19 like everything else.
Interview: “Serological tests will allow not to establish models with the part but with the whole”
To what extent can immunology be the secret to return to active life?
There are two fundamental points of science that are critical to this. Epidemiology: study, quantify and make predictions for the future of how the disease will behave. But this science can only come close to the actual incidence of infection when you have reliable figures. And that’s where immunology comes in. Because? Because in a disease where we have 4 out of 5 asymptomatic patients, if we are dealing with this population only with diagnostic tests, we are only really studying 1/5 of the infected people. Serological and immunological tests will allow not to establish models with the part, but with the whole. And it makes predictions more accurate and effective. This is important because the political measures of the situation in which we live, confinement, social distance, the resumption of social activities will be based on numbers. We have all heard of R0: it is nothing more or less than the number of people that each person infects.
But if we don’t know how many people were actually infected, is that for something?
It is an estimate. It is not precise. But what we do know with the methods we have is that an infected person transmits it to another. From the moment this value falls below one, we reduce the infection capacity. And so the epidemic tends to decrease.
How can trivializing serological tests that measure antibodies make policy decisions different?
What we will have will be decisions made in a much more informed way. Because the results are more robust. Subsequently, serological tests have revealed other things. Initially, when an agent declared an epidemic in China, there was talk of a high death rate, higher than double digits. And this was a catastrophe: it could end the human population. This is not the case. And this is important to say in terms of the perception of public opinion. It is a public health problem, it is a disease with extraordinarily severe clinical conditions, as it has not been seen in decades and decades. But with serological studies, what you are beginning to realize is that there are so many people who have had contact with infected people that the death rate is actually much lower. I wouldn’t go so far as to trivialize it and say it’s similar to seasonal flu, but it may be only slightly higher. And that makes all the difference.
Which?
From the point of view of public health. Because we are not dealing with a disease that would be the new black plague. It is a viral infection, yes, it has a serious clinical picture, even if it is mild. But it has a lower mortality rate than previously thought and reaches a fraction of the population that is very well identified. And therefore, these two data probably allow us to adopt measures that guarantee the protection of the most exposed sectors and others, more favorable to the resumption of economic activity in sectors that may be affected but do not develop diseases.
We are talking about …
Children, people of working age and who do not have other types of diseases that can be a risk factor.
“What I am saying is not to suddenly stop the most fragile population and raise children and stepchildren.”
This is a mathematical question, then comes politics.
This is a matter of public health policy. It is not just math. We leave the enclosure gradually and gradually. At the territory level, or in sectors. What I am saying is that they do not suddenly lock up the most fragile population and raise children and stepchildren. No. In terms of public investment … for example, this is what happened here at the Foundation: it was not to stop activities and invest in the safety of the population that is most at risk. And so that’s the design so we can get this out.
And what would that be? For example, in relation to grandparents and grandchildren?
At the beginning, with the opening of schools, these children go to schools and this question no longer arises. Where we have a great impact is in the homes. The results for Italy, United Kingdom, all countries, show that a large percentage of mortality occurred in households. Where there is a high density of people at risk, confined to a closed space. In such places, regular testing policies, for professionals and users, would be extremely important. Testing can only be effective if it can be implemented in the field. That is why this complementarity is important: diagnosis, immunology.
Anyone with a positive immunity test does not need to do another …
This, combined with mirror work regimes, allows us to create a system in which with much greater security we can continue to provide the best care, ensuring the return to a new normal economic activity. Especially since we already have a great economic crisis. And social, which will only tend to increase.
“To talk about long-term immunity … we don’t know. We can talk again in a year and maybe we can respond.”
Last week, the WHO itself gave mixed signals on immunity. Do you become immune or not after taking covid-19?
What we know: A significant number of affected people develop specific antibodies to this virus, but the existence of antibodies does not mean that the person is immune. What does immune mean? It involves getting infected the first time and is more protected when reinfected. We do not know yet.
Why
For a simple reason: it is a new infection. And to talk about immunity in a month, two months or long term … We can talk again in a year and maybe we can respond.
It’s a matter of time?
Exactly.But although this is very recent, we already know a lot. and we already know that the capacity of the antibodies to neutralize the virus is proportional to the amount of antibodies that the infected person has. Whoever produces the most antibodies has a serum that will be more efficient at neutralizing the virus. And this is an indirect indication that they will be more protected. And vice versa. Individuals with a lower amount of antibodies: they do not have such an important capacity to neutralize the virus. We Know We know that plasma from infected individuals can be used for patients, and there have been interesting results. It is not a scalable approach. The other important point is that in non-human primate models, after a first infection, and in a relatively short time, they are protected from the new infection.
And what do we still not know?
That is the great discussion. First: what percentage of infected individuals develop antibodies. We lack population studies that can tell us. The vast majority probably do, but we don’t know if developing antibodies means immunity for everyone. It is possible and reasonable that this is so. Because there are four more coronaviruses in the world population. What we do know about these infections is that there is an established immunity. It is not for the rest of your life, short to medium duration. And it is based not only on antibodies, but also on T cells: they do not produce antibodies but kill infected cells. In this specific case, it is too early to say.
Can you understand each person’s response to the virus and what determines death?
No, this is a great unknown. And it’s not much different in the context of covid or another type of infection. What we have already been able to define is that within this more susceptible population, the immune system is less reactive. And that will give you less ability to deal with the infection and allow you to settle more severely.
“Now what is beginning to be realized is that there will be some very important environmental factors. One of them is air quality.”
But is this the same for all diseases of this type, or not?
No, it depends. There are diseases that have a higher incidence in children. It depends a lot. But in terms of the clinical picture, it is no different from seasonal flu. In 2017 we did not go far, in Europe with 150 thousand deaths. 2011 was even worse. And there the risk group is similar, and the DGS rules are the same, vaccination for the elderly and clinical staff. When we have a vaccine, the policy will be the same. Because the priority population is the same.
Is there no difference between countries that show specific immunities?
We are witnessing a unique opportunity, a pandemic, and the virus that is distributed globally and quickly only shows that we are all virgins because of it. We have no protection. From a genetic protection point of view … it’s too early to say. Will we now find gene X in a population? There are studies in this direction. The study of the pandemic itself indicates that there will be no more protected groups or countries. Now what you are beginning to realize is that there will be some very important environmental factors. One of them is air quality. And this needs confirmation, but, for example, in Italy, the death or death rate in Lombardy is much higher than in the rest of the country. And there is a direct correlation with air quality: Lombardy has terrible quality due to its geographical nature, humidity, it is there in the pre-Alps. In the case of Italy it is very clear.
Do these theories of group immunity, which have been much discussed, really make sense?
In reality, there was no country that blindly bets on this. Even the ones we give as an example, Sweden and the Netherlands, had containment measures. Physical distancing produces profound changes in the way people relate and work. The idea of group immunity is that as we increase the percentage of individuals in contact with the virus in the population, some degree of immunity will develop. This is not proven for covid-19, but it is for other infectious agents. It would be surprising if the same did not happen. Group immunity is a level at which there is a percentage of the population that already has a degree of protection and cannot function as a vehicle to transmit the virus between people. It is a kind of biological barrier. If we multiply this by thousands of people, the epidemic can no longer spread and ends up stopping. And because such infection depends on the behavior of the group … The virus is not the enemy, the enemy is the proximity of people. Because if we are not close, the virus does not pass from one person to another. This varies greatly from one disease to another, but it is estimated that this barrier must be contaminated by around 60 to 70% of the population. The reality is that this level of group protection is critical … Because with increased immunity, the second and third possible waves will be weaker.
“With the measures we gain time. What we know today, from a scientific point of view, is incomparable with what we knew a month and a half ago. We better understand what is happening not only with the virus, but also with the behavior of the virus. epidemic in different countries. ”
The consequence of this is higher mortality, the price to pay.
We talk a lot about flattening the curve. If there are no measures, we would have cases that would skyrocket very quickly. The death rate itself was not going to change, but the number of people who were going to need intensive care. And we would run into the problem that the NHS could not respond adequately and we would have an increase in people who could die. The measures we took led to the flattening of the curve. This has immense advantages. He first gave us time to prepare. We are better prepared for a second phase from an operational and logistical point of view. And this is very important. So, we bought time and that time, what we know today, from a scientific point of view, is incomparable with what we knew a month and a half ago. We better understand what is happening not only with the virus, but also with the behavior of the epidemic in different countries. And that allows you to adjust the measurements. Now this is natural: the lower the number of cases in a first wave, the less group protection there will be.
It is a very difficult political decision to make …
Very difficult. And that, in reality, it should have on both scales what would be the ideal situation from the point of view of health and other factors: life in a society is not limited to that.
Can poverty resulting from a crisis also have an effect on immunity?
Poverty is associated with lower levels of health and well-being, which do not go exclusively through immunity, but go through many other factors: obesity, cardiovascular and metabolic diseases, diabetes. And as we know, these types of diseases are tremendous risk factors for this infection.
“Someone who has a balanced diet, with fruits, vegetables, fresh products, does not need supplements. There may even be problems with having an excess.”
What can help immunity? Food, sleep, vitamins?
Until recently, the immune system was said to be used to fight infection. In the past few decades, the immune system has been shown to serve much more, and the work of our group has been at the forefront. It is an interface with the environment as important as the nervous system, which is what allows us to be here to speak. Because? Because the cells of the immune system are able to perceive and interact with environmental factors that we have to deal with every day. Our microbiome, the hours of sleep, who we contact, and that is a completely new area that is opening horizons for us. And we are realizing the importance of this system for the preservation of our health. We are investigating the union of the two systems.
Where do vitamins come in?
We know that there are several families of white blood cells that require a certain type of vitamins to develop and perform their activity more efficiently, and that by recognizing this vitamin they can modulate the immune response making it more efficient. Vitamin D, C, A are important. Now, someone who has a balanced and normal diet (with fruits, vegetables, in fact, fresh products) does not need supplements. There may even be problems with having an excess.
What is more important?
Have a normal life. Balanced diet, a sleep pattern as normal as possible, which is a major challenge in this period, maintaining routines. And this is related to the study we published on the importance of sleep …
What hope can we have about having a vaccine?
If we had a vaccine in 18 months it would be extraordinary. Because they are processes that under normal circumstances take longer. And it is one thing to have the vaccine, another to be effective, and to be effective, when we have nothing, we will have to do studies … And then there is a need to bring the vaccine to those who need it. And this will be another challenge from a logistical point of view. We will not talk about defined populations, we will talk about everyone. So we can define policies, etc … who takes first. But it will be a great challenge for production.
There are diseases that have never been vaccinated: HIV, for example …
This is an RNA virus, there were drug trials … they didn’t go well, but the investigation is ongoing. If those drugs that are already being used could work with it, it would save us a lot of time, because its safety in use has already been proven. Regulatory steps may be exceeded.
“There is an important factor: fear. People are afraid and fear does not disappear from one moment to the next. It is progressive. And it will take longer to disappear than it took to settle.”
In practical terms, what should be said to the population to prepare them for the next step, without panicking?
It is necessary to return to normality, but normality will be possible. A new normal. Speak remotely, with masks, indoors. And there is an important factor. Fear People are afraid and fear does not disappear from one moment to another. It is progressive and will take longer to disappear than to install. It will be a long process. In terms of public health measures and in terms of economic recovery. The model that will be most socially compatible to implement will be a gradual gradual recovery and from a different territorial point of view. Because not all areas have the same impact.
We will not be able to continue thinking about the number of cases, or deaths …
At the beginning of the epidemic, the numbers we paid attention to were different. There is information that is no longer relevant. Not from a scientific or medical point of view. But as far as the message goes to the population, it becomes less important. Even on the media agenda, we began to hear a lot about the recovery, and the need to restart the economy, to take steps to help the population gain confidence and feel more secure.
This article is part of a series dedicated to Portuguese researchers and supported by: AbbVie
