We have heard many times over the past months that virologists ‘have been warning us’ about a potential pandemic. Is this how you imagined it would be?
Kevin Ariën: Respiratory viruses probably have one of the highest chances of becoming pandemic: coronaviruses, influenza viruses and paramyxoviruses all have members that can spread pandemically. Societal changes in the past 100 years made conditions easier for epidemics to spread. During the time of the 1918 Spanish flu epidemic the world’s population was 1.7 billion; now it’s almost 8 billion. Most people then were living in the countryside, travelled by foot or horse-drawn carriages. Now there are commercial airlines, immense changes in travel and trade and of course large-scale urbanisation.
In China there are 15 cities which have more than 10 million inhabitants. Cities, and the world in general, have become denser and more connected. This also accounts for the shrinking of habitats for wildlife – so that wild animals that have never been in contact with people are not that secluded anymore. Coronaviruses have jumped from animals to humans several times before… so this pandemic is not a surprise for virologists.
What about the flu viruses?
Those are close contenders when it comes to possible pandemics. There have been serious flu epidemics since 1918 as well, such as the Mexican flu epidemic of 2009, the Russian flu in 1977 and the Hong Kong flu in 1968. The H5N1 variant of avian or bird flu is for the moment a dead-end infection in humans, as it does not yet transmit well from person to person, but viruses continuously evolve.
This article was published in the 11th edition of the biannual P³ magazine.
Alarmingly, the mortality rate of some bird flu viruses in humans is around 30%. It’s no coincidence that the World Health Organization (WHO) is keeping close track of flu viruses in animals and humans. These are mostly transmitted by aquatic birds, but there have been many instances of infected poultry, in China and also in Europe. In order to prevent further spreading to and within poultry livestock, mass culling has taken place to stop the spread of flu viruses such as H5N1. By the way, the same needed to happen in mink farms in the Netherlands, because many of them tested positive for COVID-19.
Interestingly, flu viruses use different receptors in the airways to enter into birds and humans. In birds, flu viruses mainly cause gastrointestinal infections, but in people they present themselves as respiratory illnesses. So, most avian flu viruses are not well adapted to infect and propagate in our human airways. Pigs have both types of receptors that are used by avian and human flu viruses respectively. As a consequence, pigs are ‘mixing vessels’ where avian, pig and human flu strains can exchange genetic material to create new variants. These viruses might also become potentially dangerous for humans in the future.
You also mentioned paramyxoviruses. What are they?
Well known human diseases caused by paramyxoviruses are mumps and measles for example. Other paramyxoviruses have emerged more recently in humans and livestock in Australia and Southeast Asia, such as the Hendra virus (HeV) and the Nipah virus (NiV). Both are contagious, highly virulent and cause a potentially fatal disease in humans. Nipah comes from bats, then infects pigs and then goes on to humans. Hendra also originates in bats, but then it infects horses, and lastly, humans.
Let’s talk a bit about vaccines and possible treatments, because this is what the world is so eagerly awaiting. It takes years to develop a vaccine, why?
We can look at the example of the vaccine for the seasonal flu, in terms of the production process. There are about 100 sentinel sites of WHO globally, where they track year-round what is circulating in the population in terms of flu strains and their genetic composition. Based on that information, WHO then determines the composition of the vaccine. In order to make sufficient vaccines by the time the flu season is here, companies need six to eight months.
It is very likely that in the meantime the virus keeps mutating, so by the time the flu season hits, the virus might have drifted away from the vaccine strains and offer suboptimal protection. Many companies still rely on old technologies for flu vaccine development that originated in the 1950s, where vaccines are made on embryonated chicken eggs. Eggs are inoculated by the flu virus, which then replicates and from there the vaccine strain is harvested. You need about one egg for one dose of vaccine, so you can imagine the logistics of this.
There are also other, more efficient recombinant technologies but the big vaccine producers have heavily invested in the egg-based process, that now allows the production of vaccines at an affordable price and profit margins. Hence there is little incentive to change the production process. But if we are to produce vaccines for the entire global population, our development strategies and production processes require a paradigm shift.
Making vaccines for a newly emerging pathogen such as SARS-CoV-2 is still in a different league. First, you need to study the basics of this new pathogen and understand which proteins/antigens elicit strong and protective immune responses. Next, you need to express these antigens, formulate them as a vaccine, develop the right animal models for preclinical evaluation, perform phase 1 and 2 clinical studies to assess vaccine safety and finally large-scale phase 3 clinical studies need to be undertaken to assess efficacy.
At the same time, the production capacity has to be scaled up to fit the demand. This process takes time, a lot of time. For COVID-19, a vaccine is promised within 12-18 months, but we need to understand that this would be an unprecedented success. And we have not even mentioned the political and societal challenges to make this vaccine accessible to everyone in need, including for the poorest populations on this planet.
What about antivirals? For HIV they took many years to develop.
Vaccines will probably arrive before effective treatment is discovered. We know that some people were administered hydroxychloroquine (HC) in Belgian hospitals and that it appeared to benefit them. However, there is a lot of debate internationally on the use of HC and that large-scale studies have not found any benefit of HC for the treatment of COVID-19. HC is not a coronavirus-specific treatment: origin- ally it is a malaria medicine. Remdesivir, a broad-spectrum antiviral that was also tested for Ebola virus treatment, seemed to have helped reduce recovery time in some severe cases of COVID-19. HIV medication, which indeed took many years to develop, is a very specific combination drug, which stops the virus from replicating itself - it fits as perfectly as a key in a lock. Such coronavirus-specific medications are currently unavailable and will take several years to develop.
It is important to keep in mind that medicine is far more advanced now than say, 100 years ago. At the time of the Spanish flu, antibiotics, which could have saved many people from the fatal secondary infection of bacterial pneumonia, were not discovered yet. The world population in 2020 will probably not be decimated by this coronavirus, but we need to be vigilant about other known viruses and other viruses yet to arise, which are a constant threat to global public health. The scientific world, epidemiologists and virologists learn a lot from these outbreaks, so we learn more about the novel coronavirus every day.
Tell us more about the role of intermediate hosts in zoonoses. In the case of COVID-19, bats were blamed first but then we started hearing about pangolins.
Pierre Dorny: That’s one of the possibilities. It may be that the SARS-CoV-2 virus did not jump from bats to humans directly, but that the transmission chain included a so-called intermediate host. This is not uncommon: in case of MERS these were camels and for SARS they were civet cats. Pangolins are small mammals, wholly covered in scales to fend off predators. In some parts of the world, for example in China or in Ghana, their meat is considered a delicacy. Their scales are also used in traditional Chinese medicine. They are similar to what game is for Europeans: think of wild boar or deer which are on many restaurants’ menus in autumn. Similarly, civet cats are eaten in some communities as bushmeat and camels live in close contact with humans in the Middle East as livestock: there are camel farms, camel races, etc. Intermediate hosts may act as vectors for viruses to reach their definitive host and viruses may undergo certain developments in intermediate hosts. They keep adapting.
Is the definitive closing of the so-called ‘wet markets’ – the place where the corona virus is purported to have originated from – a solution?
Closing them while the pandemic is ongoing helps of course. But in many countries of the world, buying a live animal or having one slaughtered at the market is the only guarantee of fresh meat. Pangolins are an endangered species – but they are popular, so it is likely that their trade would continue underground.
In many parts of Africa, people simply have no choice but to keep hunting wild animals for protein. Bushmeat also finds its way to Europe and is sold in black markets.
As humans keep cutting the territories of wildlife down, the opportunity for contact increases. Intensive farming, where there is close proximity with animals, accelerates the transmission of airborne diseases. We need to take care of our environment and realise that we are part of a larger ecosystem: our future depends on it.
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