A pandemic is a natural catastrophic event, a gigantic, prolonged "earthquake": unpredictable, but with the certainty that sooner or later it will happen, yielding devastating health and socio-economic effects. Contrasting measures are crucial to limit further spread and to impair the action of the pathogen.
Covid-19 does not yet allow to predict what the additional impact of the continuous spread of the SARS-CoV-2 virus could be in physiopathological, epidemiological and socio-economic terms. Many questions still remain open about the near future, but scientific research is at the forefront of producing answers that are far from easy for specific therapy and prevention.
Moreover, in order to face in time and rationally any next, ineluctable pandemic danger, multidisciplinary scientific research, the biomedical and epidemiological ones in particular, must immediately think of an "(infra) anti-pandemic structure", which, with experience of the past and the present, allows to “build” effective prevention and mitigation strategies, in an integrated and unitary vision.
The pandemic caused by the new SARS-CoV-2 coronavirus can be considered the first of the global era, from the point of view of both health and socio-economic impact. The fundamental question is whether all of this was predictable. But from this one, as in a matryoshka game, further more questions arise.
Our ability to find the right answers to these questions has an importance that goes beyond the fight against Covid-19 disease. In fact, the strategies to combat other pandemics, which we will inevitably have to deal with in the future, will depend on it.
News of the emergence of new viruses capable of infecting humans in remote regions of the globe and with exotic names such as Nipah, Chikungunya, Zika, Ebola, are immediately picked up by the world press. This is because any new virus can potentially become a global threat. Fortunately, most of the time the viruses that emerge from tropical jungles or overcrowded markets in Asian metropolises do not go beyond the boundaries of the regions of origin. But it's just luck. To think that epidemics from emerging pathogens will not occur or that they will always and only be a problem for some (often of the poorest and least developed areas of the world) is not only wrong, but irresponsible, if not presumptuous, and above all very dangerous. The SARS-CoV-2 pandemic is a glaring example of the devastating effects of the emergence of a new infectious agent in the globalized society.
Every year, billions of people and goods travel by plane or ship from one continent to another. A virtual network that can be accessed with a simple smartphone or tablet, connects the entire planet, and can be accessed to follow events even far away in real time. Globalization, however, also has important health consequences. AIDS, SARS, avian flu and now SARS-CoV-2 are examples of viral infections that, starting from small outbreaks in small regions, have traveled around the world. Not to mention the problem of increasing diffusion of new pathogenic bacteria resistant to antibiotics. The speed and frequency of contacts therefore plays a dual role: on the one hand, it allows to implement coordinated responses at a global level, and on the other hand the engine itself behind the spread of outbreaks. Being ready for new epidemic events requires strategies that counterbalance these two opposite effects.
As the World Health Organization recalls: "An epidemic anywhere on Earth is just hours away from becoming a threat everywhere." Addressing these situations requires foresight, to make reliable projections of possible scenarios. Fundamental to this ability is the knowledge of the biology of pathogens, their evolutionary dynamics, the life cycle, the transmission routes, the relationship between human modification of the environment, and the appearance of new infectious agents. On the basis of this knowledge it is possible to set up prevention and contrast strategies: from epidemiological containment measures, to diagnostic techniques, to drugs, to vaccines. The speed of communication and movement, combined with the possibility of interfacing almost instantly regardless of distance, offers the possibility of creating global epidemiological surveillance networks, but also large coordinated networks of researchers, thus accelerating the process of sharing ideas, knowledge and resources. Knowing how to fully exploit these opportunities is the key to our ability to respond to the next pandemics.
In 2018, the World Health Organization added to the list of most dangerous-for-humanity emerging pathogens the so-called "X Disease" to indicate the real risk that a worldwide epidemic could be triggered by a pathogen currently unknown to cause infections in humans.
Today, "X Disease" has a name: Covid-19, caused by the new infectious agent SARS-CoV-2, and these are the challenges we face today, but which will be the same we will face also for the next epidemics:
Quickly fill gaps in knowledge of the biological characteristics of the infectious agent with a multidisciplinary approach
Define shared protocols for the implementation of monitoring and contrast measures through the application of innovative tools
Overcome the limits of preclinical/clinical development procedures, production and distribution of new drugs and vaccines with new technological solutions
Scientific research, therefore, plays a fundamental role in formulating strategies to combat not only the present pandemic, but also future ones.
The CNR Department of Biomedical Sciences, by the very nature of its mission, is unavoidably at the forefront in providing society with the necessary answers.
The DSB-CNR strategy to face the Covid-19 pandemic and prepare for future ones is divided into three fundamental pillars, further declined in specific project activities:
The COVID-19 disease caused by the SARS-CoV-2 coronavirus, is characterised by symptoms ranging from milder flu-like ones, to severe pneumonia often accompanied by an uncontrolled inflammatory response or "cytokine storm", which causes severe damage to the body . It is crucial to understand both the pathogenetic mechanisms of the virus and the genetic determinants that modulate the response to infection. Several ongoing projects at the CNR Department of Biomedical Sciences study the modulation of the immune and inflammatory response by SARS-CoV-2 and the genetic determinants that can influence individual susceptibility. Other groups are studying the neurological effects of the infection and its possible consequences on children born to mothers with COVID-19.
Understanding the pathogenic mechanisms of SARS-CoV-2 and identifying possible therapeutic targets requires an in-depth analysis of the life cycle of the virus and its molecular interactions with the host cell. Researchers of the Department, characterized by skills in biochemistry and cell biology, are aiming at identifying and characterizing the complex network of functional interactions between virus and cell proteins in different cellular and animal models (see projects list on the right: Virology and Host's response).
In the absence of effective drugs and waiting for the vaccination campaign to reach a sufficient number of people to trigger "herd immunity", to ensure the health of the population and at the same time avoid the socio-economic collapse of the country, strategies are needed for proper management of the epidemic, as well as the implementation of innovative protection systems and sensitive, accurate, fast and user-friendly diagnostic tests. Researchers from the Department of Biomedical Sciences are actively engaged in both the optimization of existing tests and the development of innovative diagnostic technologies. Furthermore, projects are underway for the development and validation of materials with antiviral properties to be incorporated into personal protective equipments.
The COVID-19 epidemic put pressure on the national health care system, highlighting some important weaknesses. Aspects that emerged as priorities are: the possibility of making early diagnoses, also through remote monitoring of patients so as not to overload the hospital facilities; the optimization of patient management paths, based on the severity and consequent levels of assistance required. The Department of Biomedical Sciences, faithful to its vocation of combining basic research with applicative aspects, has numerous projects underway for the development of innovative solutions in the field of telemedicine and clinical and environmental monitoring (see projects list on the right: Diagnostics and Devices).
Any strategy for the prevention and contrast of an infectious disease necessarily requires complex epidemiological studies. In this field DSB institutes are actively pursuing epidemiological investigations, as well as providing computational/statistical tools for data analysis (see projects list on the right: Epidemiology).
The SARS-CoV-2 pandemic has required a massive global effort to counter the spread of the infection, and vaccine development has taken place in record time. However, before mass vaccination can lead to the significant reduction, if not complete suppression, of viral circulation, many months will pass, during which more people will unfortunately contract the infection. Furthermore, vaccination will protect healthy people, but effective targeted and personalized therapies are needed to ensure health protection for the hundreds of thousands of individuals who have already contracted the virus in our country. The Department of Biomedical Sciences, thanks to the multidisciplinary approach that has always characterized its research activity, has a wide range of projects underway aimed at identifying new molecular targets and new molecules capable of blocking the virus. Furthermore, by combining in silico analyses with in vitro and in cell experimental approaches, the researchers of the Department of Biomedical Sciences are actively engaged in known drugs repositioning studies, in order to accelerate the development of effective therapies (see projects list on the right: Therapy).
According to the "4P (personalized, predictive, preventive, participated) medicine" view, one of the pillars of prevention in times of epidemics is the active involvement of the community in contagion containment practices. In order to promote "community engagement", the Department of Biomedical Sciences promotes training and education initiatives for both healthcare personnel and the general public (see projects list on the right: Third Mission).
One of the first pandemic disasters we heard about was in 541 A.C. It was a real massacre, because there was no knowledge and no tools to defend people. Over the centuries, new measures were always adopted for the prevention and treatment of those affected, which today allow us to deal with the new pandemics with greater expertise.
Let's see what we learned from the past ...
At the beginning, historians could only tell that the plague arrived from Egypt to Constantinople in 541 A.C., by sea and with caravans. About a million people died; physicians had no idea how the disease spread and how to cure it. The remedies were reduced to hot baths, to try to get the "moods" considered "bad" out of the body of the sick. Those who survived became, in most cases, immune to the disease and were usually no longer infected with it.
In the Middle Ages, although leprosy was already known in the second millennium bc.C., leper hospitals were set in Europe and other parts of the world, outside the cities, where pathologic pople was forced to live because of their appearance and fear of contagion. These structures were re-resumed in the centuries to the present day; among the figures who dedicated themselves to the care of lepers, we remember Albert Schweitzer (pictured) and Mother Teresa of Calcutta.
To avoid the contagion of the plague that struck Florence at the end of the 1300s, the brigade of ten young people, to whom Giovanni Boccaccio had the stories of the "Decameron" tell, took refuge in the hills around the city. This is an example of a preventive measure adopted by healthy people, aware of the possibility of getting sick, if they remained in the contiguity of an active outbreak.
In Venice, in the 1300s, it was understood that the plague was quickly spread by the sailors landing. For this reason the Venetians first, followed by the Pisans and the Marseillais, imposed, in case of ascertained symptoms, a period of 30 days, fixed at 40 in the following century by the Republic of Venice, before disembarking the survivors of the crews affected by the disease, considered (likely) no longer contagious.
From the first year of the epidemic, the Venetians established a magistracy with health duties. In 1403 the first dedicated hospital was founded, with the aim of completely isolating the infected subjects, on the island of Santa Maria di Nazareth called Nazarethum (name soon changed to "lazaretto"), to take care of them, even with the limits of knowledge of the time.
The "monatti", cited by Alessandro Manzoni in the "Promessi Sposi", recounting the plague of Milan in 1630, were employees in charge of transporting the sick persons to the hospital or the corpses. They were sentenced to death people, prisoners, as well as people who had recovered from the disease and were so immune from it, the only ones who were allowed to bring relief to the newly infected or to provide for the burial of the deceased.
In the late 1700s, Jenner discovered the first vaccine to immunize against smallpox, which caused epidemics around the world. The establishment of vaccination made it possible to completely eradicate smallpox in the 1970s, through strategies based on mass vaccination.
The possibility of carrying out large-scale vaccinations has made it possible, after 140 years, to obtain a very different outcome from the cholera epidemics in southern Italy. In 1837, thousands of infected people died throughout southern Italy. In 1973, thanks to the sanitary cordon mainly limited to the Neapolitan area, and to a sweeping vaccination of the population, the damage in terms of lost human lives was extremely reduced (about 25 victims). At the same time, with the arrival of Albert Bruce Sabin's vaccine and the consequent mass vaccination, the effects of polio, which caused thousands of deaths, was drastically reduced.
Modern intensive therapies and the first artificial respirators, were introduced as necessary supports to counter polio, which still claimed thousands of victims in the 1950s, due to flaccid paralysis resulting from infection, capable of depriving the patient of respiratory function.
During the Spanish flu, which also affected Italy between 1918 and 1920, precise provisions were established throughout Europe, to counter the spread of the virus, which the population had to follow. The dissemination of these ordinances was possible, at the time, only by affixing of posters, being the only large-scale communication media available to the health authorities. Some of these recommendations recall the current restrictive measures adopted by governments for the containment and management of the Covid-19 emergency.
During the last months of World War I, the first case of Spanish flu was recorded: health systems risked to collapse, as for the quick spread of the virus, and it was necessary to create emergency hospital facilities, able to accommodate the huge number of infected patients. Instead, the funeral mortuaries couldn't keep up with the victims.
The observance of anti-contagion norms adopted during the Spanish flu, modified many aspects of life such as traveling, moving and relating to other people, and the continued and widespread use of measures to protect the respiratory tract, the main access channel of contagion. At the time of the Asian flu pandemic of 1957-58 years, the use of the mask became mandatory and widely diffused, as a protective aid to be worn while performing normal daily activities, at school or at work.
The so-called "community engagement", that is the involvement of the population during the Ebola epidemic in Central Africa since the 1970s, was a measure that necessarily had to find a compromise between respect for religious traditions and the protection of human health. This approach made it possible to contain the epidemic and limit its spread also, and above all, at the local level.